Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multipl...Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multiple types of cancer by pan cancer analyses.Methods:UALCAN and TIMER2 database were utilized to evaluate PRDM16 expression in cancer patients.Gene Expression Profiling Interactive Analysis was employed to analyze the overall survival and disease-free survival across all The Cancer Genome Atlas Program tumors.Using the cBioPortal tool,we analyzed the mutation features of PRDM16 for the The Cancer Genome Atlas Program tumors,then utilized the Encyclopedia of RNA Interactomes database to predict the miRNA-mRNA relationships associated with the PRDM16 for all tumors.Results:The expression level of PRDM16 in the tumor tissues is lower than that in the normal tissues.Interesting,the high expression of PRDM16 has a positive effect on the prognosis of kidney clear cell carcinoma and lung adenocarcinoma,but not conducive to the prognosis of most cancers.In multiple cancer types,the expression of PRDM16 was significantly positively correlated with immune infiltration of cancer-associated fibroblasts.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated that PRDM16 may be related to transcriptional misregulation pathway in cancer.We identified potential miRNAs that play regulatory roles of PRDM16 in kidney clear cell carcinoma and lung adenocarcinoma.Conclusion:PRDM16 is expressed in different cancers,it can be used as a biomarker for prognosis of pan-cancer and is associated with immune infiltration.展开更多
Objective This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosisantigen Rv0674. Methods To evaluate thediagnostic potential and antigenicity of Rv0674, IgG was eval...Objective This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosisantigen Rv0674. Methods To evaluate thediagnostic potential and antigenicity of Rv0674, IgG was evaluated using ELISA and interferon (IFN)-γ was done by using ELISpot assay among TB patients and healthy donors. For immunogenicity evaluation, BALB/c mice were immunized with Rv0674. Cytokine production was determined by cytokine release assay using an ELISA kit, and the antibodies were tested using ELISA. Results The results of serum Elisa tests showed that Rv0674 specific immunoglobulin G (IgG) response was higher in TB patients than negative controls. And Rv0674 had good performance in serological test with sensitivity and specificity of 77.1% and 81.1%, respectively. While it shows poor sensitivity and specificity of 26.23% and 79.69% for IFN-γ tests. In BALB/c mice, Rv0674 adjuvant by DDA/PolyI:C could also induce a high level of IFN-γ, interleukin-2 and interleukin-6 as well as a high IgG titer in both high-and low-dose groups indicating that Rv0674 is essential in humoral and cellular immunity. Moreover, the cytokine profile and IgG isotypecharacterized Rv0674 as a Th1/Th2-mixed-type protective immunity with the predominance of Th1 cytokines. Conclusion Rv0674 may be a good potential candidate for the development of TB serological diagnosis and a new TB vaccine.展开更多
Objective In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were al...Objective In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were also discussed in this study. Methods Milk was preprocessed with 4% NaOH. Then, mycobacteria were isolated from the milk sample on L-J medium. The isolate was identified using multiple loci Polymerase Chain Reaction (PCR) and multi-locus sequence analysis with 16S rRNA, sodA, hsp65, and ITS genes. The drug sensitivity of the isolate to 27 antibiotics was tested through alamar blue assay. Results Smooth, moist, pale yellow colonies appeared on the L-J medium within a week after inoculation. Based on the results of multiple loci PCR analysis, the isolate was preliminarily identified as non-tuberculous mycobacteria. The 16S rRNA, SodA, hsp65, and ITS gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities, respectively, with those of the published reference strains of Mycobacteriurn elephantis (M. elephantis). The drug sensitivity results showed that the strain is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin, levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin, ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline. Conclusion To the best of our knowledge, this study is initially to report the isolation of M. elephantis from the milk of a cow with mastitis in China.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD) is characterized by deregulated hepatic lipid metabolism;however, the association between MAFLD development and mitochondrial dysfunction has yet to be confi...Metabolic dysfunction-associated fatty liver disease(MAFLD) is characterized by deregulated hepatic lipid metabolism;however, the association between MAFLD development and mitochondrial dysfunction has yet to be confirmed. Herein, we employed highresolution respirometry, blue native polyacrylamide gelelectrophoresis-basedin-gelactivity measurement and immunoblot analysis to assess mitochondrial function in obesity-induced mouse models with varying degrees of MAFLD. Results showed a slight but significant decrease in hepatic mitochondrial respiration in some MAFLD mice compared to mice fed a standard diet. However, the activities and levels of mitochondrial oxidative phosphorylation complexes remained unchanged during obesity-induced MAFLD progression. These results suggest that mitochondrial function,particularly oxidative phosphorylation, was mildly affected duringo besity-induced MAFLD development. Moreover, transcriptome profiling of mouse and human liver tissues with varying degrees of MAFLD revealed that the decreased activation of mitochondria-related pathways was only associated with MAFLD of a high histological grade, whereas the major regulators of mitochondrial biogenesis were not altered in mice or humans during MAFLD development. Collectively, our results suggest that impaired hepatic mitochondrial function is not closely associated with obesity-induced MAFLD. Therefore,therapeutic strategies targeting mitochondria for the treatment of MAFLD should be reconsidered.展开更多
Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its activity.Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming...Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its activity.Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis,which plays an important role in tumor progression.This study aims to elucidate how PDK1 pro-motes breast cancer progression.We found that PDK1 was highly expressed in breast cancer tissues,and PDK1 knockdown reduced the proliferation,migration,and tumorigenicity of breast cancer cells and inhibited the HIF-1α(hypoxia-inducible factor 1α)pathway.Further investigation showed that PDK1 promoted the protein stability of HIF-1αby reducing the level of ubiquitination of HIF-1α.The HIF-1αprotein levels were dependent on PDK1 kinase activity.Furthermore,HIF-1αphosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer cells.The phosphorylation of HIF-1αat Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1αwith von Hippel-Lindau and prolyl hydroxylase domain.We also found that PDK1 enhanced HIF-1αtranscriptional ac-tivity.In summary,PDK1 enhances HIF-1αprotein stability by phosphorylating HIF-1αat Ser451 and promotes HIF-1αtranscriptional activity by enhancing the binding of HIF-1αto P300.PDK1 and HIF-1αform a positive feedback loop to promote breast cancer progression.展开更多
With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogene...With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.展开更多
BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to trea...BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver,among which Dendrobium nobile Lindl.powder has been affirmed by many doctors and patients to be effective.However,there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.AIM To survey the effect of combining Dendrobium nobile Lindl.powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.METHODS Eighty patients with mild to moderate NAFLD participated in this retrospective study,classified into two groups:The observation group(n=40)and the control group(n=40).In November 2020 and November 2022,the study was conducted at People’s Hospital of Chongqing Liang Jiang New Area.The control group received standard treatment,while the observation group received Dendrobium nobile Lindl.powder based on the control group.The study compared differences in traditional Chinese medicine clinical syndrome scores,liver fibrosis treatment,liver function indicators,lipid levels,and serum inflammatory factor levels before and after treatment,and we calculated the incidence of adverse reactions for both groups.RESULTS The total effective rate was 97.50%in the observation group and 72.5%in the control group.After 8 weeks of treatment,the main and secondary symptom scores remarkably decreased,especially in the observation group(P<0.05),and there was a significant reduction in the serum levels of hyaluronic acid(HA),laminin(LN),human rocollagen III(PC III),and collagen type IV(CIV).The levels of HA,LN,PC III,and CIV were significantly lower in the observation group(P<0.05).After 8 weeks,both groups indicated remarkable improvements in liver function and blood lipid levels,with the observation group having even lower levels(P<0.05).Serum levels of interleukin-1β,tumor necrosis factor-α,and interleukin-8 also dropped significantly.The observation group had a lower rate of adverse reactions(5.00%)compared to the control group(22.50%).CONCLUSION Adding Dendrobium nobile Lindl.powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease.It also enhances hepatic function and lipid profile,ameliorates liver fibrosis indices,and lowers the risk of side effects.Consequently,this therapeutic protocol shows promise for clinical implementation and dissemination.展开更多
With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical...With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical treatments.This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient.The most promising potential treatment options rely on stem cellbased therapies.Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function.Clinical approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing capacity.We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential.Given the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care.展开更多
The flexible wearable sensors with excellent stretchability,high sensitivity and good biocompatibility are significantly required for continuously physical condition tracking in health management and rehabilitation mo...The flexible wearable sensors with excellent stretchability,high sensitivity and good biocompatibility are significantly required for continuously physical condition tracking in health management and rehabilitation monitoring.Herein,we present a high-performance wearable sensor.The sensor is prepared with nanocomposite hydrogel by using silk fibroin(SF),polyacrylamide(PAM),polydopamine(PDA)and graphene oxide(GO).It can be used to monitor body motions(including large-scale and small-scale motions)as well as human electrophysiological(ECG)signals with high sensitivity,wide sensing range,and fast response time.Therefore,the proposed sensor is promising in the fields of rehabilitation,motion monitoring and disease diagnosis.展开更多
AIM: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines. METHODS: Western blotting was used to analyze the expression profile of Axl glycoprote...AIM: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines. METHODS: Western blotting was used to analyze the expression profile of Axl glycoprotein in mouse hepa-tocellular carcinoma cell line Hca-F treated with tunicamycin and PNGase F 3-(4,5)-dimethylthiazol(-zyl)-3,5- diphenyltetrazolium bromide (MTT) assay, extracellular matrix (ECM) invasion assay (in vitro ) and tumor metastasis assay (in vivo ) were utilized to evaluate the effect of Axl deglycosylation on the Hca-F cell proliferation, invasion and lymphatic metastasis. RESULTS: Tunicamycin and PNGase F treatment markedly inhibited Axl glycoprotein synthesis and expression, proliferation, invasion, and lymphatic metastasis both in vitro and in vivo . In the MTT assay, proliferation was apparent in untreated Hca-F cells compared with treated Hca-F cells. In the ECM invasion assay (in vitro ), treated cells passed through the ECMatrix gel in significantly smaller numbers than untreated cells (tunicamycin 5 μg/mL: 68 ± 8 vs 80 ± 9, P=0.0222; 10 μg/mL: 50 ± 6vs 80 ± 9,P=0.0003; 20 μg/mL: 41 ± 4 vs 80 ± 9, P=0.0001); (PNGase F 8 h: 66 ± 7 vs 82 ± 8, P=0.0098; 16 h: 49 ± 4 vs 82 ± 8, P=0.0001; 24 h: 34 ± 3 vs 82 ± 8, P=0.0001). In the tumor metastasis assay (in vivo ), average lymph node weights of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 0.84 ± 0.21 g vs 0.72 ± 0.19 g, P=0.3237; 10 μg/mL: 0.84 ± 0.21 g vs 0.54 ± 0.11 g, P=0.0113; 20 μg/mL: 0.84 ± 0.21 g vs 0.42 ± 0.06 g, P=0.0008); (PNGase F 8 h: 0.79 ± 0.15 g vs 0.63 ± 0.13 g, P=0.0766; 16 h: 0.79 ± 0.15 g vs 0.49 ± 0.10 g, P=0.0022; 24 h: 0.79 ± 0.15 g vs 0.39 ± 0.05 g, P=0.0001). Also, average lymph node volumes of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 815 ± 61 mm 3 vs 680 ± 59 mm 3 , P=0.0613; 10 μg/mL: 815 ± 61 mm 3 vs 580 ± 29 mm 3 , P=0.0001; 20 μg/mL: 815 ± 61 mm 3 vs 395 ± 12 mm 3 , P=0.0001); (PNGase F 8 h: 670 ± 56 mm 3 vs 581 ± 48 mm 3 , P=0.0532; 16 h: 670 ± 56 mm 3 vs 412 ± 22 mm 3 , P=0.0001; 24 h: 670 ± 56 mm 3 vs 323 ± 11 mm 3 , P=0.0001). CONCLUSION: Alteration of Axl glycosylation can at-tenuate neoplastic lymphatic metastasis. Axl N-glycans may be a universal target for chemotherapy.展开更多
Detection of mercury ions(Hg^(2+))in actual samples is of significant importance due to the toxicity of Hg^(2+)to human health.In this work,a simple tetraphenylethene(TPE)derived fluorescent probe TPE-Hg based on aggr...Detection of mercury ions(Hg^(2+))in actual samples is of significant importance due to the toxicity of Hg^(2+)to human health.In this work,a simple tetraphenylethene(TPE)derived fluorescent probe TPE-Hg based on aggregation-induced emission(AIE)mechanism was synthesized.TPE-Hg can visually recognize Hg^(2+)in THF/HEPES(1:9,v/v,HEPES 20 mmol/L,pH 7.3)system with rapid response,strong anti-interference ability,large Stokes shift(203 nm),and low detection limit(7.548×10^(-7)mol/L).The results show that Hg^(2+)triggered elimination of TPE-Hg lead to releasing of an AIE-active compound 2 is responsible to the sensing mechanism.TPE-Hg is applicable to detect Hg^(2+)in actual water samples and image Hg^(2+)in living MCF-7 cells.In addition,TPE-Hg is suitable to assay the Hg^(2+)level in seafood and tea samples,and it is alsoapplicable intest strips.展开更多
All cells release extracellular vesicles(EVs)as part of their normal physiology.As one of the subtypes,exosomes(EXOs)have an average size range of approximately 40 nm e160 nm in diameter.Benefiting from their inherent...All cells release extracellular vesicles(EVs)as part of their normal physiology.As one of the subtypes,exosomes(EXOs)have an average size range of approximately 40 nm e160 nm in diameter.Benefiting from their inherent immunogenicity and biocompatibility,the utility of autologous EXOs has the potential for both disease diagnosis/treatment.EXOs are generally employed as“bioscaffolds”and the whole diagnostic and therapeutic effects are mainly ascribed to exogenous cargos on the EXOs,such as proteins,nucleic acids,and chemotherapeutic agents and fluorophores delivered into specific cells or tissues.Surface en-gineering of EXOs for cargo loadings is one of the prerequisites for EXO-mediated diagnosis/treatment.After revisiting EXO-mediated diagnosis/treatment,the most popular strategies to directly undertake loadings of exogenous cargos on EXOs include genetic and chemical en-gineering.Generally,genetically-engineered EXOs can be merely produced by living organisms and intrinsically face some drawbacks.However,chemical methodologies for engineered EXOs diversify cargos and extend the functions of EXOs in the diagnosis/treatment.In this review,we would like to elucidate different chemical advances on the molecular level of EXOs along with the critical design required for diagnosis/treatment.Besides,the prospects of chemical engineering on the EXOs were critically addressed.Nevertheless,the superiority of EXO-medi-ated diagnosis/treatment via chemical engineering remains a challenge in clinical translation and trials.Furthermore,more chemical crosslinking on the EXOs is expected to be explored.Despite substantial claims in the literature,there is currently no review to exclusively summa-rize the chemical engineering to EXOs for diagnosis/treatment.We envision chemical engi-neering of EXOs will encourage more scientists to explore more novel technologies for a wider range of biomedical applications and accelerate the successful translation of EXO-based drug“bioscaffolds”from bench to bedside.展开更多
Biothiols,including cysteine(Cys),homocysteine(Hey),and glutathione(GSH) play important roles in physiological processes,and the detection of thiol using fluorescent probes has attracted attention due to their high se...Biothiols,including cysteine(Cys),homocysteine(Hey),and glutathione(GSH) play important roles in physiological processes,and the detection of thiol using fluorescent probes has attracted attention due to their high sensitivity and selectively and invasive on-time imaging.However,the similar structures and reactivity of these biothiols present great challenges for selective detection.This review focused on the the "aromatic nucleophilic substitution-rearrangement(SNAr-rearrangement) mechanism",which provided a powerful tool to design fluorescent probes for the discrimination between biothiols.We classify the fluorescent probes according to types of fluorophores,such as difluoroboron dipyrromethene(BODIPY),nitrobenzoxadiazole(NBD),cyanine,pyronin,naphthalimide,coumarin,and so on.We hope this review will inspire exploration of new fluorescent probes for biothiols and other relevant analytes.展开更多
Antibody-based PD-IIPD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast ...Antibody-based PD-IIPD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre- existing T-cell function to modulate antitumor immunity. in this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/ PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-IIPD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural informationwill benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.展开更多
Bats are connected with the increasing numbers of emerging and re-emerging viruses that may break the species barrier and spread into the human population. Coronaviruses are one of the most common viruses discovered i...Bats are connected with the increasing numbers of emerging and re-emerging viruses that may break the species barrier and spread into the human population. Coronaviruses are one of the most common viruses discovered in bats, which were considered as the natural source of recent human-susceptible coronaviruses, i.e. SARS-COV and MERS-CoV. Our previous study reported the discovery of a bat-derived putative cross-family recombinant coronavirus with a reovirus gene p10, named as Ro-BatCoV GCCDC1. In this report, through a two-year follow-up of a special bat population in one specific cave of south China, we illustrate that Ro-BatCoV GCCDC1 persistently circulates among bats. Notably, through the longitudinal observation, we identified the dynamic evolution of Ro-BatCoV GCCDC1 in bats represented by continuously recombination events. Our study provides the first glimpse of the virus evolution in one longitudinally observed bat population cohort and underlines the surveillance and pre-warning of potential interspecies transmittable viruses in bats.展开更多
Dear Editor,Blockade of PD-1/PD-L1 signaling pathway by monoclonal antibodies(MAbs)to release the anti-tumor activity of pre-existing tumor specific T cell immunity has initiated a new era for tumor immunotherapy.Admi...Dear Editor,Blockade of PD-1/PD-L1 signaling pathway by monoclonal antibodies(MAbs)to release the anti-tumor activity of pre-existing tumor specific T cell immunity has initiated a new era for tumor immunotherapy.Administration of anti-PD-1 MAbs(nivolumab and pembrolizumab)in either monotherapy or in combination with anti-CTLA-4 MAbs or traditional chemother-apy has achieved a tumor regression rate of 30%-50%in dealing with melanoma,non-small cell lung cancer,etc.(Larkin et al.,2015).展开更多
Hepatocellular carcinoma (HCC), a major subtype of liver cancers, is a prevalent human malignancy worldwide. In men, HCC is the fifth frequently diagnosed cancer but the second most common cause of cancer death. In ...Hepatocellular carcinoma (HCC), a major subtype of liver cancers, is a prevalent human malignancy worldwide. In men, HCC is the fifth frequently diagnosed cancer but the second most common cause of cancer death. In women, it ranks seventh in cancer diagnosis and sixth in cancer-related death (Jemal et al., 2011). Unlike some other cancers, such as breast cancer and colon cancer, the molecular etiology of HCC re- mains largely unknown. Infection of hepatitis virus is considered as a major risk factor in the development of liver cancers (Parkin, 2006). Currently, there are limited options to treat HCC except for chemotherapy. Elucidating molecular mechanism of hepatocyte transformation will help develop new treatments for cancer. The widely accepted multi-step progression of carcinogenesis consists of genetic alterations which regulate cell proliferation, apoptosis and so on (Vogelstein and Kinzler, 1993). Moreover, abnormal activation of signaling pathways has been proposed as an oncogenic driver for cancer development. For example, Kras activation occurs in 7% of human liver cancer patients. Activated Kras is sufficient to induce robust liver tumorigenesis in transgenic animal models (Nguyen et al., 2011).展开更多
To the Editor: We read an interesting paper entitled, "A Pilot Study of Quantitative Loop-mediated Isothermal Amplification-guided Target Therapies for Hospital-acquired Pneumonia" published in Chinese Medical Jour...To the Editor: We read an interesting paper entitled, "A Pilot Study of Quantitative Loop-mediated Isothermal Amplification-guided Target Therapies for Hospital-acquired Pneumonia" published in Chinese Medical Journal recently.展开更多
The combination of upconverting nanoparticles(UCNPs)and immunochromatography has become a widely used and promising new detection technique for point-of-care testing(POCT).However,their low luminescence efficiency,non...The combination of upconverting nanoparticles(UCNPs)and immunochromatography has become a widely used and promising new detection technique for point-of-care testing(POCT).However,their low luminescence efficiency,non-specific adsorption,and image noise have always limited their progress toward practical applications.Recently,artificial intelligence(AI)has demonstrated powerful representational learning and generalization capabilities in computer vision.We report for the first time a combination of AI and upconversion nanoparticle-based lateral flow assays(UCNP-LFAs)for the quantitative detection of commercial internet of things(IoT)devices.This universal UCNPs quantitative detection strategy combines high accuracy,sensitivity,and applicability in the field detection environment.By using transfer learning to train AI models in a small self-built database,we not only significantly improved the accuracy and robustness of quantitative detection,but also efficiently solved the actual problems of data scarcity and low computing power of POCT equipment.Then,the trained AI model was deployed in IoT devices,whereby the detection process does not require detailed data preprocessing to achieve real-time inference of quantitative results.We validated the quantitative detection of two detectors using eight transfer learning models on a small dataset.The AI quickly provided ultra-high accuracy prediction results(some models could reach 100%accuracy)even when strong noise was added.Simultaneously,the high flexibility of this strategy promises to be a general quantitative detection method for optical biosensors.We believe that this strategy and device have a scientific significance in revolutionizing the existing POCT technology landscape and providing excellent commercial value in the in vitro diagnostics(IVD)industry.展开更多
基金This study was financially supported by the Young Teachers Support Program of Hubei University of Chinese Medicine(2021ZZX025)Hubei Province College Students’innovation and entrepreneurship training program(S202210507018).
文摘Background:Positive regulatory domain-containing 16(PRDM16)plays a key role in brown adipose transcription,but its function in cancer is unclear.Our research to investigate the potential roles of PRDM16 across multiple types of cancer by pan cancer analyses.Methods:UALCAN and TIMER2 database were utilized to evaluate PRDM16 expression in cancer patients.Gene Expression Profiling Interactive Analysis was employed to analyze the overall survival and disease-free survival across all The Cancer Genome Atlas Program tumors.Using the cBioPortal tool,we analyzed the mutation features of PRDM16 for the The Cancer Genome Atlas Program tumors,then utilized the Encyclopedia of RNA Interactomes database to predict the miRNA-mRNA relationships associated with the PRDM16 for all tumors.Results:The expression level of PRDM16 in the tumor tissues is lower than that in the normal tissues.Interesting,the high expression of PRDM16 has a positive effect on the prognosis of kidney clear cell carcinoma and lung adenocarcinoma,but not conducive to the prognosis of most cancers.In multiple cancer types,the expression of PRDM16 was significantly positively correlated with immune infiltration of cancer-associated fibroblasts.Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analysis indicated that PRDM16 may be related to transcriptional misregulation pathway in cancer.We identified potential miRNAs that play regulatory roles of PRDM16 in kidney clear cell carcinoma and lung adenocarcinoma.Conclusion:PRDM16 is expressed in different cancers,it can be used as a biomarker for prognosis of pan-cancer and is associated with immune infiltration.
基金National Science and Technology Major Project of China [2018ZX10731301-002]
文摘Objective This study aimed to characterize the diagnostic and vaccine potential of a novel Mycobacterium tuberculosisantigen Rv0674. Methods To evaluate thediagnostic potential and antigenicity of Rv0674, IgG was evaluated using ELISA and interferon (IFN)-γ was done by using ELISpot assay among TB patients and healthy donors. For immunogenicity evaluation, BALB/c mice were immunized with Rv0674. Cytokine production was determined by cytokine release assay using an ELISA kit, and the antibodies were tested using ELISA. Results The results of serum Elisa tests showed that Rv0674 specific immunoglobulin G (IgG) response was higher in TB patients than negative controls. And Rv0674 had good performance in serological test with sensitivity and specificity of 77.1% and 81.1%, respectively. While it shows poor sensitivity and specificity of 26.23% and 79.69% for IFN-γ tests. In BALB/c mice, Rv0674 adjuvant by DDA/PolyI:C could also induce a high level of IFN-γ, interleukin-2 and interleukin-6 as well as a high IgG titer in both high-and low-dose groups indicating that Rv0674 is essential in humoral and cellular immunity. Moreover, the cytokine profile and IgG isotypecharacterized Rv0674 as a Th1/Th2-mixed-type protective immunity with the predominance of Th1 cytokines. Conclusion Rv0674 may be a good potential candidate for the development of TB serological diagnosis and a new TB vaccine.
基金supported by the project 81401647 of Natural Science Foundation of ChinaProject 2014SKLID104 of State Key Laboratory for Infectious Diseases Prevention and Controlprojects 16411967900 of Science and Technology Commission of Shanghai Municipality
文摘Objective In this study, milk from a cow with mastitis was analyzed to determine the presence of mycobacterial infection. Milk quality and security problems pertaining to the safe consumption of dairy products were also discussed in this study. Methods Milk was preprocessed with 4% NaOH. Then, mycobacteria were isolated from the milk sample on L-J medium. The isolate was identified using multiple loci Polymerase Chain Reaction (PCR) and multi-locus sequence analysis with 16S rRNA, sodA, hsp65, and ITS genes. The drug sensitivity of the isolate to 27 antibiotics was tested through alamar blue assay. Results Smooth, moist, pale yellow colonies appeared on the L-J medium within a week after inoculation. Based on the results of multiple loci PCR analysis, the isolate was preliminarily identified as non-tuberculous mycobacteria. The 16S rRNA, SodA, hsp65, and ITS gene sequences of the isolate exhibited 99%, 99%, 99%, and 100% similarities, respectively, with those of the published reference strains of Mycobacteriurn elephantis (M. elephantis). The drug sensitivity results showed that the strain is resistant to isoniazid, p-aminosalicylic acid, and trimesulf but is sensitive to ofloxacin, rifampicin, amikacin, capreomycin, moxifloxacin, kanamycin, levofloxacin, cycloserine, ethambutol, streptomycin, tobramycin, rifabutin, ciprofloxacin, linezolid, cefoxitin, clarithromycin, and minocycline. Conclusion To the best of our knowledge, this study is initially to report the isolation of M. elephantis from the milk of a cow with mastitis in China.
基金This research was supported by the National Natural Science Foundation of China(Key Program:81830071)Zhejiang Provincial Natural Science Foundation of China(LY19H040004 and Key Program:LR20H200001)Zhejiang Provincial Health Science and Technology Plan(2015KYB238)。
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD) is characterized by deregulated hepatic lipid metabolism;however, the association between MAFLD development and mitochondrial dysfunction has yet to be confirmed. Herein, we employed highresolution respirometry, blue native polyacrylamide gelelectrophoresis-basedin-gelactivity measurement and immunoblot analysis to assess mitochondrial function in obesity-induced mouse models with varying degrees of MAFLD. Results showed a slight but significant decrease in hepatic mitochondrial respiration in some MAFLD mice compared to mice fed a standard diet. However, the activities and levels of mitochondrial oxidative phosphorylation complexes remained unchanged during obesity-induced MAFLD progression. These results suggest that mitochondrial function,particularly oxidative phosphorylation, was mildly affected duringo besity-induced MAFLD development. Moreover, transcriptome profiling of mouse and human liver tissues with varying degrees of MAFLD revealed that the decreased activation of mitochondria-related pathways was only associated with MAFLD of a high histological grade, whereas the major regulators of mitochondrial biogenesis were not altered in mice or humans during MAFLD development. Collectively, our results suggest that impaired hepatic mitochondrial function is not closely associated with obesity-induced MAFLD. Therefore,therapeutic strategies targeting mitochondria for the treatment of MAFLD should be reconsidered.
基金supported by grants from the National Natural Science Foundation of China(No.82073255)the Foundation of Chongqing Municipal Education Commission(China)(No.HZ2021006).
文摘Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its activity.Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis,which plays an important role in tumor progression.This study aims to elucidate how PDK1 pro-motes breast cancer progression.We found that PDK1 was highly expressed in breast cancer tissues,and PDK1 knockdown reduced the proliferation,migration,and tumorigenicity of breast cancer cells and inhibited the HIF-1α(hypoxia-inducible factor 1α)pathway.Further investigation showed that PDK1 promoted the protein stability of HIF-1αby reducing the level of ubiquitination of HIF-1α.The HIF-1αprotein levels were dependent on PDK1 kinase activity.Furthermore,HIF-1αphosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer cells.The phosphorylation of HIF-1αat Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1αwith von Hippel-Lindau and prolyl hydroxylase domain.We also found that PDK1 enhanced HIF-1αtranscriptional ac-tivity.In summary,PDK1 enhances HIF-1αprotein stability by phosphorylating HIF-1αat Ser451 and promotes HIF-1αtranscriptional activity by enhancing the binding of HIF-1αto P300.PDK1 and HIF-1αform a positive feedback loop to promote breast cancer progression.
基金supported in part by research grants from the Natural Science Foundation of China(No.82102696 to JF)the 2019 Funding for Postdoctoral Research(Chongqing Human Resources and Social Security Bureau No.298 to JF)the National Institutes of Health(No.CA226303 to TCH,DE030480 to RRR).
文摘With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport strategies.Except for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.
基金Supported by the Chongqing Science and Health Joint Medical Research Project,No.2022MSXM133the First Batch of Key Disciplines on Public Health in Chongqing,Natural Science Foundation of Chongqing,No.CSTB2022NSCQ-MSX1522.
文摘BACKGROUND Nonalcoholic fatty liver disease(NAFLD)encompasses a variety of liver conditions impacting individuals who consume minimal or no alcohol.Recently,traditional Chinese medicine has been gradually used to treat mild to moderate fatty liver,among which Dendrobium nobile Lindl.powder has been affirmed by many doctors and patients to be effective.However,there is limited research on combining this treatment with standard therapies for mild to moderate NAFLD.AIM To survey the effect of combining Dendrobium nobile Lindl.powder with standard treatment on liver function and lipid metabolism disorder in patients with mild to moderate NAFLD.METHODS Eighty patients with mild to moderate NAFLD participated in this retrospective study,classified into two groups:The observation group(n=40)and the control group(n=40).In November 2020 and November 2022,the study was conducted at People’s Hospital of Chongqing Liang Jiang New Area.The control group received standard treatment,while the observation group received Dendrobium nobile Lindl.powder based on the control group.The study compared differences in traditional Chinese medicine clinical syndrome scores,liver fibrosis treatment,liver function indicators,lipid levels,and serum inflammatory factor levels before and after treatment,and we calculated the incidence of adverse reactions for both groups.RESULTS The total effective rate was 97.50%in the observation group and 72.5%in the control group.After 8 weeks of treatment,the main and secondary symptom scores remarkably decreased,especially in the observation group(P<0.05),and there was a significant reduction in the serum levels of hyaluronic acid(HA),laminin(LN),human rocollagen III(PC III),and collagen type IV(CIV).The levels of HA,LN,PC III,and CIV were significantly lower in the observation group(P<0.05).After 8 weeks,both groups indicated remarkable improvements in liver function and blood lipid levels,with the observation group having even lower levels(P<0.05).Serum levels of interleukin-1β,tumor necrosis factor-α,and interleukin-8 also dropped significantly.The observation group had a lower rate of adverse reactions(5.00%)compared to the control group(22.50%).CONCLUSION Adding Dendrobium nobile Lindl.powder to standard treatment has been found to remarkably improve symptoms and reduce inflammation in patients with mild to moderate fatty liver disease.It also enhances hepatic function and lipid profile,ameliorates liver fibrosis indices,and lowers the risk of side effects.Consequently,this therapeutic protocol shows promise for clinical implementation and dissemination.
基金The contributing authors’laboratories were supported in part by research grants from the National Institutes of Health(CA226303,DE020140 to TCH and RRR)the U.S.Department of Defense(OR130096 to JMW)+4 种基金the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust(R.R.R.,T.C.H.,and G.A.A.)the Scoliosis Research Society(TCH and MJL),and the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906).This project was also supported in part by the National Center for Advancing Translational Sciences of the National Institutes of Health through Grant Number UL1 TR000430.EC was supported by the Summer Research Program of The University of Chicago Pritzker School of Medicine.TCH was also supported by the Mabel Green Myers Research Endowment Fund and The University of Chicago Orthopaedic Alumni Fund.Funding sources were not involved in the study designin the collection,analysis and interpretation of datain the writing of the reportand in the decision to submit the paper for publication.
文摘With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical treatments.This requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven insufficient.The most promising potential treatment options rely on stem cellbased therapies.Stem cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell function.Clinical approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing capacity.We aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic potential.Given the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care.
基金Smart Medicine Research Project of Chongqing Medical University in 2020(YJSZHYX202022)Smart Medicine Research Project of Chongqing Medical University(ZHYX2019019)Chongqing Research Program of Basic Research and Frontier Technology(cstc2018jcyjAX0165).
文摘The flexible wearable sensors with excellent stretchability,high sensitivity and good biocompatibility are significantly required for continuously physical condition tracking in health management and rehabilitation monitoring.Herein,we present a high-performance wearable sensor.The sensor is prepared with nanocomposite hydrogel by using silk fibroin(SF),polyacrylamide(PAM),polydopamine(PDA)and graphene oxide(GO).It can be used to monitor body motions(including large-scale and small-scale motions)as well as human electrophysiological(ECG)signals with high sensitivity,wide sensing range,and fast response time.Therefore,the proposed sensor is promising in the fields of rehabilitation,motion monitoring and disease diagnosis.
基金Supported by Creating Team Item of Liaoning Province, No.2008T033the Technological Natural Fund Item of Liaoning Province, China, No. 20092164
文摘AIM: To investigate the effects of Axl deglycosylation on tumor lymphatic metastases in mouse hepatocellular carcinoma cell lines. METHODS: Western blotting was used to analyze the expression profile of Axl glycoprotein in mouse hepa-tocellular carcinoma cell line Hca-F treated with tunicamycin and PNGase F 3-(4,5)-dimethylthiazol(-zyl)-3,5- diphenyltetrazolium bromide (MTT) assay, extracellular matrix (ECM) invasion assay (in vitro ) and tumor metastasis assay (in vivo ) were utilized to evaluate the effect of Axl deglycosylation on the Hca-F cell proliferation, invasion and lymphatic metastasis. RESULTS: Tunicamycin and PNGase F treatment markedly inhibited Axl glycoprotein synthesis and expression, proliferation, invasion, and lymphatic metastasis both in vitro and in vivo . In the MTT assay, proliferation was apparent in untreated Hca-F cells compared with treated Hca-F cells. In the ECM invasion assay (in vitro ), treated cells passed through the ECMatrix gel in significantly smaller numbers than untreated cells (tunicamycin 5 μg/mL: 68 ± 8 vs 80 ± 9, P=0.0222; 10 μg/mL: 50 ± 6vs 80 ± 9,P=0.0003; 20 μg/mL: 41 ± 4 vs 80 ± 9, P=0.0001); (PNGase F 8 h: 66 ± 7 vs 82 ± 8, P=0.0098; 16 h: 49 ± 4 vs 82 ± 8, P=0.0001; 24 h: 34 ± 3 vs 82 ± 8, P=0.0001). In the tumor metastasis assay (in vivo ), average lymph node weights of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 0.84 ± 0.21 g vs 0.72 ± 0.19 g, P=0.3237; 10 μg/mL: 0.84 ± 0.21 g vs 0.54 ± 0.11 g, P=0.0113; 20 μg/mL: 0.84 ± 0.21 g vs 0.42 ± 0.06 g, P=0.0008); (PNGase F 8 h: 0.79 ± 0.15 g vs 0.63 ± 0.13 g, P=0.0766; 16 h: 0.79 ± 0.15 g vs 0.49 ± 0.10 g, P=0.0022; 24 h: 0.79 ± 0.15 g vs 0.39 ± 0.05 g, P=0.0001). Also, average lymph node volumes of the untreated Hca-F group compared with treated Hca-F groups (tunicamycin 5 μg/mL: 815 ± 61 mm 3 vs 680 ± 59 mm 3 , P=0.0613; 10 μg/mL: 815 ± 61 mm 3 vs 580 ± 29 mm 3 , P=0.0001; 20 μg/mL: 815 ± 61 mm 3 vs 395 ± 12 mm 3 , P=0.0001); (PNGase F 8 h: 670 ± 56 mm 3 vs 581 ± 48 mm 3 , P=0.0532; 16 h: 670 ± 56 mm 3 vs 412 ± 22 mm 3 , P=0.0001; 24 h: 670 ± 56 mm 3 vs 323 ± 11 mm 3 , P=0.0001). CONCLUSION: Alteration of Axl glycosylation can at-tenuate neoplastic lymphatic metastasis. Axl N-glycans may be a universal target for chemotherapy.
基金funded by the National Natural Science Foundation of China(Nos.22278038,21878023),the Program for Distinguished Professor of Liaoning Province.
文摘Detection of mercury ions(Hg^(2+))in actual samples is of significant importance due to the toxicity of Hg^(2+)to human health.In this work,a simple tetraphenylethene(TPE)derived fluorescent probe TPE-Hg based on aggregation-induced emission(AIE)mechanism was synthesized.TPE-Hg can visually recognize Hg^(2+)in THF/HEPES(1:9,v/v,HEPES 20 mmol/L,pH 7.3)system with rapid response,strong anti-interference ability,large Stokes shift(203 nm),and low detection limit(7.548×10^(-7)mol/L).The results show that Hg^(2+)triggered elimination of TPE-Hg lead to releasing of an AIE-active compound 2 is responsible to the sensing mechanism.TPE-Hg is applicable to detect Hg^(2+)in actual water samples and image Hg^(2+)in living MCF-7 cells.In addition,TPE-Hg is suitable to assay the Hg^(2+)level in seafood and tea samples,and it is alsoapplicable intest strips.
基金supported by the National Natural Science Foundation of China(No.81972023)the Natural Science Foundation of Chongqing City,China(No.cstc2021jcyj-msxm0172)+2 种基金the Science and Technology Research Program of Chongqing Education Commission of China(No.KJQN201900425)Creative Research Group of CQ University(China)(No.CXQT21017)the Program for Youth Innovation in Future Medicine from Chongqing Medical University(China).
文摘All cells release extracellular vesicles(EVs)as part of their normal physiology.As one of the subtypes,exosomes(EXOs)have an average size range of approximately 40 nm e160 nm in diameter.Benefiting from their inherent immunogenicity and biocompatibility,the utility of autologous EXOs has the potential for both disease diagnosis/treatment.EXOs are generally employed as“bioscaffolds”and the whole diagnostic and therapeutic effects are mainly ascribed to exogenous cargos on the EXOs,such as proteins,nucleic acids,and chemotherapeutic agents and fluorophores delivered into specific cells or tissues.Surface en-gineering of EXOs for cargo loadings is one of the prerequisites for EXO-mediated diagnosis/treatment.After revisiting EXO-mediated diagnosis/treatment,the most popular strategies to directly undertake loadings of exogenous cargos on EXOs include genetic and chemical en-gineering.Generally,genetically-engineered EXOs can be merely produced by living organisms and intrinsically face some drawbacks.However,chemical methodologies for engineered EXOs diversify cargos and extend the functions of EXOs in the diagnosis/treatment.In this review,we would like to elucidate different chemical advances on the molecular level of EXOs along with the critical design required for diagnosis/treatment.Besides,the prospects of chemical engineering on the EXOs were critically addressed.Nevertheless,the superiority of EXO-medi-ated diagnosis/treatment via chemical engineering remains a challenge in clinical translation and trials.Furthermore,more chemical crosslinking on the EXOs is expected to be explored.Despite substantial claims in the literature,there is currently no review to exclusively summa-rize the chemical engineering to EXOs for diagnosis/treatment.We envision chemical engi-neering of EXOs will encourage more scientists to explore more novel technologies for a wider range of biomedical applications and accelerate the successful translation of EXO-based drug“bioscaffolds”from bench to bedside.
基金financially supported by the National Natural Science Foundation of China (No. 21525206)
文摘Biothiols,including cysteine(Cys),homocysteine(Hey),and glutathione(GSH) play important roles in physiological processes,and the detection of thiol using fluorescent probes has attracted attention due to their high sensitivity and selectively and invasive on-time imaging.However,the similar structures and reactivity of these biothiols present great challenges for selective detection.This review focused on the the "aromatic nucleophilic substitution-rearrangement(SNAr-rearrangement) mechanism",which provided a powerful tool to design fluorescent probes for the discrimination between biothiols.We classify the fluorescent probes according to types of fluorophores,such as difluoroboron dipyrromethene(BODIPY),nitrobenzoxadiazole(NBD),cyanine,pyronin,naphthalimide,coumarin,and so on.We hope this review will inspire exploration of new fluorescent probes for biothiols and other relevant analytes.
基金This work was supported by the National Basic Research Program (973 Program) (Nos. 2013CB531502 and 2014CB542503), the National Natural Science Foundation of China (Grant Nos. 31390432 and 31500722), Grand S&T project of China Health and Family Planning Commission (2013ZX10004608-002 and 2016ZX10004201-009), the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS XDB08020100). GFG is supported partly as a leading principal investigator of the NSFC Innovative Research Group (81321063).
文摘Antibody-based PD-IIPD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre- existing T-cell function to modulate antitumor immunity. in this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/ PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-IIPD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural informationwill benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.
基金supported by the National Key Research and Development Program of China(2017YFC1200202)the National Natural Science Foundation of China(81290342,81461168030)+3 种基金the Major Special Projects for Infectious Disease Research of China(2016ZX10004222-003)China National Grand S&T Special Project(2014ZX10004-001-006)supported by CAS-TWAS President’s Fellowship of the University of Chinese Academy of Sciences(UCAS)and The World Academy of Sciences(TWAS)a leading principle investigator of the NSFC Innovative Research Group(81621091)
文摘Bats are connected with the increasing numbers of emerging and re-emerging viruses that may break the species barrier and spread into the human population. Coronaviruses are one of the most common viruses discovered in bats, which were considered as the natural source of recent human-susceptible coronaviruses, i.e. SARS-COV and MERS-CoV. Our previous study reported the discovery of a bat-derived putative cross-family recombinant coronavirus with a reovirus gene p10, named as Ro-BatCoV GCCDC1. In this report, through a two-year follow-up of a special bat population in one specific cave of south China, we illustrate that Ro-BatCoV GCCDC1 persistently circulates among bats. Notably, through the longitudinal observation, we identified the dynamic evolution of Ro-BatCoV GCCDC1 in bats represented by continuously recombination events. Our study provides the first glimpse of the virus evolution in one longitudinally observed bat population cohort and underlines the surveillance and pre-warning of potential interspecies transmittable viruses in bats.
基金supported by the National Natural Science Foundation of China(82161148008 and 81971501)the National Key Research and Development Program of China(2021YFC2301400,2020YFA0708103,and 2021YFC0863300)the Excellent Young Scientist Program of the National Natural Science Foundation of China(81822040)。
基金This work was supported by the National Natural Science Founda-tion of China(Grant Nos.31390432 and 31500722)the National Basic Research Program(973 Program)(NO.2013CB531502)+1 种基金We also thank Yuanyuan Chen and Zhenwel Yang from Institute of Biophysics,Chinese Academy of Sciences for their technical support in the SPR assayG.F.G.is a leading prinoiple Investigator of NSFC Innovative Research Group(Grant No.81621091).
文摘Dear Editor,Blockade of PD-1/PD-L1 signaling pathway by monoclonal antibodies(MAbs)to release the anti-tumor activity of pre-existing tumor specific T cell immunity has initiated a new era for tumor immunotherapy.Administration of anti-PD-1 MAbs(nivolumab and pembrolizumab)in either monotherapy or in combination with anti-CTLA-4 MAbs or traditional chemother-apy has achieved a tumor regression rate of 30%-50%in dealing with melanoma,non-small cell lung cancer,etc.(Larkin et al.,2015).
基金financially supported through grants from National Natural Science Foundation of China(Nos.3147135931271563 and 81572076)+1 种基金the Ministry of Science and Technology of China(Nos.2011CB944002 and2013CB945000)the Chinese Academy of Sciences(No.XDA01010108)
文摘Hepatocellular carcinoma (HCC), a major subtype of liver cancers, is a prevalent human malignancy worldwide. In men, HCC is the fifth frequently diagnosed cancer but the second most common cause of cancer death. In women, it ranks seventh in cancer diagnosis and sixth in cancer-related death (Jemal et al., 2011). Unlike some other cancers, such as breast cancer and colon cancer, the molecular etiology of HCC re- mains largely unknown. Infection of hepatitis virus is considered as a major risk factor in the development of liver cancers (Parkin, 2006). Currently, there are limited options to treat HCC except for chemotherapy. Elucidating molecular mechanism of hepatocyte transformation will help develop new treatments for cancer. The widely accepted multi-step progression of carcinogenesis consists of genetic alterations which regulate cell proliferation, apoptosis and so on (Vogelstein and Kinzler, 1993). Moreover, abnormal activation of signaling pathways has been proposed as an oncogenic driver for cancer development. For example, Kras activation occurs in 7% of human liver cancer patients. Activated Kras is sufficient to induce robust liver tumorigenesis in transgenic animal models (Nguyen et al., 2011).
文摘To the Editor: We read an interesting paper entitled, "A Pilot Study of Quantitative Loop-mediated Isothermal Amplification-guided Target Therapies for Hospital-acquired Pneumonia" published in Chinese Medical Journal recently.
基金The authors thank the financial support from the National Natural Science Foundation of China(61905033 and 62122017).
文摘The combination of upconverting nanoparticles(UCNPs)and immunochromatography has become a widely used and promising new detection technique for point-of-care testing(POCT).However,their low luminescence efficiency,non-specific adsorption,and image noise have always limited their progress toward practical applications.Recently,artificial intelligence(AI)has demonstrated powerful representational learning and generalization capabilities in computer vision.We report for the first time a combination of AI and upconversion nanoparticle-based lateral flow assays(UCNP-LFAs)for the quantitative detection of commercial internet of things(IoT)devices.This universal UCNPs quantitative detection strategy combines high accuracy,sensitivity,and applicability in the field detection environment.By using transfer learning to train AI models in a small self-built database,we not only significantly improved the accuracy and robustness of quantitative detection,but also efficiently solved the actual problems of data scarcity and low computing power of POCT equipment.Then,the trained AI model was deployed in IoT devices,whereby the detection process does not require detailed data preprocessing to achieve real-time inference of quantitative results.We validated the quantitative detection of two detectors using eight transfer learning models on a small dataset.The AI quickly provided ultra-high accuracy prediction results(some models could reach 100%accuracy)even when strong noise was added.Simultaneously,the high flexibility of this strategy promises to be a general quantitative detection method for optical biosensors.We believe that this strategy and device have a scientific significance in revolutionizing the existing POCT technology landscape and providing excellent commercial value in the in vitro diagnostics(IVD)industry.