Comparative transcriptomic analysis reveals the molecular changes of acute pancreatitis in experimental models

BACKGROUND Acute pancreatitis(AP)encompasses a spectrum of pancreatic inflammatory conditions,ranging from mild inflammation to severe pancreatic necrosis and multisystem organ failure.Given the challenges associated with obtaining human pancreatic samples,research on AP predominantly relies on animal models.In this study,we aimed to elucidate the fundamental molecular mechanisms underlying AP using various AP models.AIM To investigate the shared molecular changes underlying the development of AP across varying severity levels.METHODS AP was induced in animal models through treatment with caerulein alone or in combination with lipopolysaccharide(LPS).Additionally,using Ptf1αto drive the specific expression of the hM3 promoter in pancreatic acinar cells transgenic C57BL/6J-hM3/Ptf1α(cre)mice were administered Clozapine N-oxide to induce AP.Subsequently,we conducted RNA sequencing of pancreatic tissues and validated the expression of significantly different genes using the Gene Expression Omnibus(GEO)database.RESULTS Caerulein-induced AP showed severe inflammation and edema,which were exacerbated when combined with LPS and accompanied by partial pancreatic tissue necrosis.Compared with the control group,RNA sequencing analysis revealed 880 significantly differentially expressed genes in the caerulein model and 885 in the caerulein combined with the LPS model.Kyoto Encyclopedia of Genes and Genomes enrichment analysis and Gene Set Enrichment Analysis indicated substantial enrichment of the TLR and NOD-like receptor signaling pathway,TLR signaling pathway,and NF-κB signaling pathway,alongside elevated levels of apoptosis-related pathways,such as apoptosis,P53 pathway,and phagosome pathway.The significantly elevated genes in the TLR and NOD-like receptor signaling pathways,as well as in the apoptosis pathway,were validated through quantitative real-time PCR experiments in animal models.Validation from the GEO database revealed that only MYD88 concurred in both mouse pancreatic tissue and human AP peripheral blood,while TLR1,TLR7,RIPK3,and OAS2 genes exhibited marked elevation in human AP.The genes TUBA1A and GADD45A played significant roles in apoptosis within human AP.The transgenic mouse model hM3/Ptf1α(cre)successfully validated significant differential genes in the TLR and NOD-like receptor signaling pathways as well as the apoptosis pathway,indicating that these pathways represent shared pathological processes in AP across different models.CONCLUSION The TLR and NOD receptor signaling pathways play crucial roles in the inflammatory progression of AP,notably the MYD88 gene.Apoptosis holds a central position in the necrotic processes of AP,with TUBA1A and GADD45A genes exhibiting prominence in human AP.

MicroRNA regulatory pattern in spinal cord ischemia-reperfusion injury

After spinal cord injury, dysregulated miRNAs appear and can participate in inflammatory responses, as well as the inhibition of apoptosis and axon regeneration through multiple pathways. However, the functions of miRNAs in spinal cord ischemia-reperfusion injury progression remain unclear. miRCURY LNATM Arrays were used to analyze miRNA expression profiles of rats after 90 minutes of ischemia followed by reperfusion for 24 and 48 hours. Furthermore, subsequent construction of aberrantly expressed miRNA regulatory patterns involved cell survival, proliferation, and apoptosis. Remarkably, the mitogen-activated protein kinase(MAPK) signaling pathway was the most significantly enriched pathway among 24-and 48-hour groups. Bioinformatics analysis and quantitative reverse transcription polymerase chain reaction confirmed the persistent overexpression of miR-22-3 p in both groups. These results suggest that the aberrant miRNA regulatory network is possibly regulated MAPK signaling and continuously affects the physiological and biochemical status of cells, thus participating in the regulation of spinal cord ischemia-reperfusion injury. As such, miR-22-3 p may play sustained regulatory roles in spinal cord ischemia-reperfusion injury. All experimental procedures were approved by the Animal Ethics Committee of Jilin University, China [approval No. 2020(Research) 01].

Key genes expressed in different stages of spinal cord ischemia/reperfusion injury ischemia/reperfusion injury

The temporal expression of microRNA after spinal cord ischemia/reperfusion injury is not yet fully understood. In the present study, we established a model of spinal cord ischemia in Sprague-Dawley rats by clamping the abdominal aorta for 90 minutes, before allowing reperfusion for 24 or 48 hours. A sham-operated group underwent surgery but the aorta was not clamped. The damaged spinal cord was removed for hematoxylin-eosin staining and RNA extraction. Neuronal degeneration and tissue edema were the most severe in the 24- hour reperfusion group, and milder in the 48-hour reperfusion group. RNA amplification, labeling, and hybridization were used to obtain the microRNA expression profiles of each group. Bioinformatics analysis confirmed tour differentially expressed microRNAs （miR-22-3p, miR-743b-3p, miR-201-5p and miR-144-5p） and their common target genes （Tmem69 and Cxcll0）. Compared with the sham group, miR- 22-3p was continuously upregulated in all three ischemia groups but was highest in the group with 11o reperfusion, whereas miR-743b-3p, miR-201-5p and miR-144-5p were downregulated in the three ischemia groups. We have successfully identified the key genes expressed at different stages of spinal cord ischemia/reperfusion injury, which provide a reference for future investigations into the mechanism of spinal cord injury.

Surgical treatment of hepatocellular carcinoma with inferior vena cava tumor thrombus: a new classification for surgical guidance

BACKGROUND: Hepatic resection is the main treatment modality for hepatic tumors. Advances in diagnostic technique, preoperative preparation, surgical technique, and postoperative management increased the success rate. The present study aimed to evaluate hepatectomy and resection of inferior vena cava tumor thrombus (IVCTT) in patients with hepatocellular carcinoma, and the relationship between IVCTT classification and selection of surgical technique. METHODS: We retrospectively reviewed 13 patients with hepatocellular carcinoma who had undergone hepatectomy with IVCTT resection between May 1997 and August 2009. Age, gender, diagnosis, findings of physical examination, results of preoperative laboratory investigations, radiological examination, criteria for resection, postoperative pathological results, incisions, operative technique, intraoperative transfusion, drains, and intraoperative and postoperative complications were evaluated for all patients. RESULTS: Type Ⅰ IVCTT (10 patients) was posterior to the liver and below the diaphragm; type Ⅱ IVCTT (2 patients) was above the diaphragm but still outside the atrium; and type Ⅲ IVCTT (1 patient) was above the diaphragm and in the right atrium. Type Ⅰ was treated by radical hepatectomy and removal of IVCTT with total hepatic vascular exclusion. Type Ⅱ was treated by radical hepatectomy and removal of IVCTT by incision of the diaphragm. Type Ⅲ was treated by hepatectomy and resection of the thrombus from the right atrium under cardiopulmonary bypass. There were no surgical complications and one patient has been survived for 4 years with cancer-free status. The median survival time was 18.2 months, and the 1-and 2-year survival rates were 53.8% and 15.4%, respectively. CONCLUSION: Surgical treatment is safe and feasible for treatment of IVCTT in patients with hepatocellular carcinoma, and surgical resectability can be judged according to the classification of tumor thrombus.

Effects of microtubule-associated protein tau expression on neural stem cell migration after spinal cord injury

Our preliminary proteomics analysis suggested that expression of microtubule-associated protein tau is elevated in the spinal cord after injury. Therefore, the first aim of the present study was to examine tau expression in the injured spinal cord. The second aim was to determine whether tau can regulate neural stem cell migration, a critical factor in the successful treatment of spinal cord injury. We established rat models of spinal cord injury and injected them with mouse hippocampal neural stem cells through the tail vein. We used immunohistochemistry to show that the expression of tau protein and the number of migrated neural stem cells were markedly increased in the injured spinal cord. Furthermore, using a Transwell assay, we showed that neural stem cell migration was not affected by an elevated tau concentration in the outer chamber, but it was decreased by changes in intracellular tau phosphorylation state. These results demonstrate that neural stem cells have targeted migration capability at the site of injury, and that although tau is not a chemokine for targeted migration of neural stem cells, intracellular tau phosphorylation/dephosphorylation can inhibit cell migration.

Exercise promotes motor functional recovery in rats with corticospinal tract injury:anti-apoptosis mechanism

Studies have shown that exercise interventions can improve functional recovery after spinal cord injury, but the mechanism of action remains unclear. To investigate the mechanism, we estab-lished a unilateral corticospinal tract injury model in rats by pyramidotomy, and used a single pellet reaching task and horizontal ladder walking task as exercise interventions postoperatively. Functional recovery of forelimbs and forepaws in the rat models was noticeably enhanced after the exercises. Furthermore, TUNEL staining revealed signiifcantly fewer apoptotic cells in the spinal cord of exercised rats, and western blot analysis showed that spinal cord expression of the apopto-sis-related protein caspase-3 was signiifcantly lower, and the expression of Bcl-2 was signiifcantly higher, while the expression of Bax was not signiifantly changed after exercise, compared with the non-exercised group. Expression of these proteins decreased with time after injury, towards the levels observed in sham-operated rats, however at 4 weeks postoperatively, caspase-3 expression remained signiifcantly greater than in sham-operated rats. The present ifndings indicate that a re-duction in apoptosis is one of the mechanisms underlying the improvement of functional recovery by exercise interventions after corticospinal tract injury.

Self-assembly to monolayer graphene film with high electrical conductivity

Monolayer chemically converted graphene （CCG） nanosheets can be homogeneously self-assembled onto silicon wafer modified by 3-aminopr- opyl triethoxysilane （APTES） to form very thin graphene film. The CCG film was characterized by FT-IR, XRD, SEM, TEM and AFM. Results show that CCG sheets formed monolayer film after assembled onto silicon wafer and there is a very tight chemical bond between sheets and wafer. Furthermore, the electrical measurements revealed that the monolayer graphene film has an excellent electrical conductivity.

Selective ablation of type 3 adenylyl cyclase in somatostatin-positive interneurons produces anxiety-and depression-like behaviors in mice

BACKGROUND Major depressive disorder(MDD)is a highly disabling psychiatric syndrome associated with deficits of specific subpopulations of cortical GABAergic interneurons;however,the underlying molecular mechanism remains unknown.Type 3 adenylyl cyclase(ADCY3,AC3),which is important for neuronal excitability,has been implicated in MDD in a genome-wide association study in humans.Moreover,a study reported that ablation of AC3 in mice caused similar symptoms as MDD patients.AIM To determine if disruption of the AC3 gene in different subtypes of GABAergic interneurons of mice causes depression-like behaviors.METHODS Using immunohistochemistry,we investigated the expression of AC3 in two major subtypes GABAergic interneurons:Somatostatin-positive(SST+)and parvalbumin-positive(PV+)neurons.Genetic manipulations were used to selectively disrupt AC3 expression in SST+or PV+interneurons.A series of behavior tests including rotarod test,open field test(OFT),elevated plus maze test(EPM),forced swimming test(FST),and tail suspension test(TST)were used to evaluate the motor ability,anxiety-and depression-like behaviors,respectively.RESULTS Our results indicate that approximately 90.41%of SST+and 91.22%of PV+interneurons express AC3.After ablation of AC3 in SST+interneurons,the mice spent comparable time in the center area in OFT,but significantly less time in the open arms and low frequency of entries to the open arms in EPM.Furthermore,these mice showed prolonged immobility in FST and more freezing in TST.However,there were no significant changes in these behaviors after specific disruption of AC3 in PV+interneurons.CONCLUSION This study indicates that ablation of AC3 in SST+interneurons of mice increases anxiety-and depression-like behaviors in mice,supporting the general hypothesis that decreased AC3 activity may play a role in human depression.

1990-2019年中国疾病负担趋势分析

目的了解我国疾病负担现状及其在1990-2019年的变化趋势。方法利用全球疾病负担研究(Global Burden of Disease,GBD 2019)数据,分析导致不同年龄、性别的中国人群伤残调整生命年(disability-adjusted life year,DALY)损失的疾病顺位变化及其在1990-2019年的变化率,探究影响我国居民健康的主要危险因素变化情况。结果2019年,我国全部疾病的DALY损失达3.8亿万人年,总DALY率从1990年的34832.88/10万降至2019年的26871.41/10万,下降幅度达22.86%。30年间,中风、缺血性心脏病、慢性阻塞性肺疾病始终是导致我国人群DALY损失的前几位病因,其中,女性DALY损失以慢性非传染性疾病居多,男性则以癌症及道路交通伤害为主。各年龄段人群影响因素不同,0~9岁、10~24岁、25~49岁、50~74岁及75岁以上各年龄段人群的DALY损失分别较1990年变化了-87.07%、-57.11%、2.13%、53.33%及129.72%。烟草、高血压、饮食风险、空气污染是影响我国人群健康的重要危险因素,高体重指数对人群健康的影响持续增强。结论1990-2019年,中国居民总体健康状况有所改善,其中非传染性疾病所占比重较大,老年人群的疾病负担逐渐增加,需要针对不同年龄段及风险人群采取相应的有效预防措施,加强对高风险人群的监测,以进一步降低疾病负担。

Treatment of liver metastases from uveal melanoma: a retrospective single-center analysis

BACKGROUND:Metastatic liver melanoma is a rare event in the Chinese population with extremely poor prognosis.Any treatment that controls a metastatic hepatic lesion potentially prolongs survival.This study aimed to evaluate the survival of patients with isolated liver metastases from uveal melanoma treated with partial hepatectomy or non-surgical management and to find the best therapeutic modality for these patients.METHODS:From January 1996 to September 2008,eight patients with liver metastases secondary to uveal melanoma were admitted to our hospital.Five patients underwent partial hepatectomy and 3 received other treatments(TACE,RFA,PEI).Their medical records were reviewed and overall survival was analyzed.RESULTS:The patients comprised 3 men and 5 women,with a median age of 44 years.Six patients presented with liver metastases at the time the primary tumor was diagnosed.The interval from the diagnosis of uveal melanoma to liver metastasis in the remaining 2 patients was 9.5 and 32.5 months,respectively.The median survival after the treatment of liver metastasis was 11.5 and 7.5 months in the surgical and nonsurgical groups,respectively.There was no procedure-related mortality in the whole study cohort.CONCLUSIONS:Partial hepatectomy or other therapies were safe and feasible for isolated liver metastases from uveal mela-noma.Aggressive treatment with multidisciplinary modalities may result in prolonged survival.

Characteristics of mRNA dynamic expression related to spinal cord ischemia/reperfusion injury:a transcriptomics study

Following spinal cord ischemia/reperfusion injury,an endogenous damage system is immediately activated and participates in a cascade reaction.It is difficult to interpret dynamic changes in these pathways,but the examination of the transcriptome may provide some information.The transcriptome reflects highly dynamic genomic and genetic information and can be seen as a precursor for the proteome.We used DNA microarrays to measure the expression levels of dynamic evolution-related m RNA after spinal cord ischemia/reperfusion injury in rats.The abdominal aorta was blocked with a vascular clamp for 90 minutes and underwent reperfusion for 24 and 48 hours.The simple ischemia group and sham group served as controls.After rats had regained consciousness,hindlimbs showed varying degrees of functional impairment,and gradually improved with prolonged reperfusion in spinal cord ischemia/reperfusion injury groups.Hematoxylin-eosin staining demonstrated that neuronal injury and tissue edema were most severe in the 24-hour reperfusion group,and mitigated in the 48-hour reperfusion group.There were 8,242 differentially expressed m RNAs obtained by Multi-Class Dif in the simple ischemia group,24-hour and 48-hour reperfusion groups.Sixteen m RNA dynamic expression patterns were obtained by Serial Test Cluster.Of them,five patterns were significant.In the No.28 pattern,all differential genes were detected in the 24-hour reperfusion group,and their expressions showed a trend in up-regulation.No.11 pattern showed a decreasing trend in m RNA whereas No.40 pattern showed an increasing trend in m RNA from ischemia to 48 hours of reperfusion,and peaked at 48 hours.In the No.25 and No.27 patterns,differential expression appeared only in the 24-hour and 48-hour reperfusion groups.Among the five m RNA dynamic expression patterns,No.11 and No.40 patterns could distinguish normal spinal cord from pathological tissue.No.25 and No.27 patterns could distinguish simple ischemia from ischemia/reperfusion.No.28 pattern could analyze the need for inducing reperfusion injury.The study of specific pathways and functions for different dynamic patterns can provide a theoretical basis for clinical differential diagnosis and treatment of spinal cord ischemia/reperfusion injury.

Fine motor skill training enhances functional plasticity of the corticospinal tract after spinal cord injury

Following central nervous system injury, axonal sprouts form distal to the injury site and extend into the denervated area, reconstructing neural circuits through neural plasticity. How to facilitate this plasticity has become the key to the success of central nervous system repair. It remains controversial whether fine motor skill training contributes to the recovery of neurological function after spinal cord injury. Therefore, we established a rat model of unilateral corticospinal tract injury using a pyramidal tract cutting method. Horizontal ladder crawling and food ball grasping training procedures were conducted 2 weeks before injury and 3 days after injury. The neurological function of rat forelimbs was assessed at 1, 2, 3, 4, and 6 weeks after injury. Axon growth was observed with biotinylated dextran amine anterograde tracing in the healthy corticospinal tract of the denervated area at different time periods. Our results demonstrate that compared with untrained rats, functional recovery was better in the forelimbs and forepaws of trained rats. The number of axons and the expression of growth associated protein 43 were increased at the injury site 3 weeks after corticospinal tract injury. These findings confirm that fine motor skill training promotes central nervous system plasticity in spinal cord injury rats.

Modified insulin-like growth factor 1 containing collagen-binding domain for nerve regeneration

Insulin-like growth factor 1 （IGF-I） is a potential nutrient for nerve repair. However, it is impractical as a therapy because of its limited half- life, rapid clearance, and limited target specificity. To achieve targeted and long-lasting treatment, we investigated the addition of a binding structure by fusing a collagen-binding domain to IGF- 1. After confirming its affinity for collagen, the biological activity of this construct was examined by measuring cell proliferation after transfection into PC12 and Schwann cells using a 3-（4,5-dimethyl-2-thiazolyl）-2,5-di- phenyl-2-H-tetrazolium bromide assay. Immunofluorescence staining was conducted to detect neurofilament and microtubule-associated protein 2 expression, while real time-polymerase chain reaction was utilized to determine IGF-1 receptor and nerve growth/actor mRNA expression. Our results demonstrate a significant increase in collagen-binding activity of the recombinant protein compared with IGF-1. Moreover, the recombinant protein promoted proliferation of PC12 and Schwann cells, and increased the expression of neurofilament and microtubule-associated protein 2. Importantly, the recombinant protein also stimulated sustained expression of IGF-1 receptor and nerve growth factor mRNA for days. These results show that the recombinant protein achieved the goal of targeting and long-lasting treatment, and thus could become a clinically used factor for promoting nerve regeneration with a prolonged therapeutic effect.

sp^(3)-like defect structure of hetero graphene-carbon nanotubes for promoting carrier transfer and stability

Three-dimensional(3 D) hybrid of nanocarbons is a very promising way to the high-performance design of electrocatalysis materials.However,sp^(3)-like defect structure,a combination of high strength and conduction of graphene and carbon nanotubes(CNTs) is rarely reported.Herein,3 D neural-like hybrids of graphene(from reduced graphene oxide) and carbon nanotubes(CNTs) have been integrated via sp^(3)-like defect structure by a hydrothermal approach.The sp^(3)-like defect structure endows 3 D nanocarbon hybrids with an enhanced carrier transfer,high structural stability,and electrocatalytic durability.The neural-like structure is shown to demonstrate a cascade effect of charges and significant performances regarding bio-electrocatalysis and lithium-sulfur energy storage.The concept and mechanism of "sp^(3)-like defect structure" are proposed at an atomic/nanoscale to clarify the generation of rational structure as well as the cascade electron transfer.

Pregnancy outcome after intracytoplasmic sperm injection with strontium oocyte activation in a globozoospermic patient

Dear Editor, I am Dr Xiao-Yu Yang, from the Center of Clinical Reproductive Medicine in the First Affiliated Hospital at the NanJing Medical University, Nanjing, China. We present here a case report of a globo- zoospermic patient whose partner became pregnant after intracyto- plasmic sperm injection （ICSI） with assisted oocyte activation （AOA）.

Priapulid worms from the Cambrian of China shed light on reproduction in early animals

In the recent years,exceptional fossil sites have revealed astonishing details on the anatomy,lifestyles and behaviour of Cambrian animals but surprisingly,very little is known about one of their most vital features,reproduction.We describe here in situ eggs(clusters of 3 to 30 oocytes)in the tube-dwelling priapulid worm Paraselkirkia sinica from the Cambrian Stage 3 Xiaoshiba Lagerstätte(ca.514 Ma,South China).These oocytes were accommodated within paired tubular ovaries located in the posterior half of the primary body cavity as in modern meiobenthic priapulid worms,thus indicating that the general organization of female tubular gonads in priapulid worms has remained virtually unchanged for half a billion years.Our findings provide for the first time,key information on the reproductive organs and strategies of early ecdysozoans,a huge animal clade that dominated Cambrian marine ecosystems and accounts for a large part of today’s biodiversity(e.g.arthropods).Moreover,we also emphasize the critical role of ecology on the reproductive strategies and lifestyles of both modern and Cambrian worms.

Multiple roles for cholinergic signaling in pancreatic diseases

Cholinergic nerves are widely distributed throughout the human body and participate in various physiological activities,including sensory,motor,and visceral activities,through cholinergic signaling.Cholinergic signaling plays an important role in pancreatic exocrine secretion.A large number of studies have found that cholinergic signaling overstimulates pancreatic acinar cells through muscarinic receptors,participates in the onset of pancreatic diseases such as acute pancreatitis and chronic pancreatitis,and can also inhibit the progression of pancreatic cancer.However,cholinergic signaling plays a role in reducing pain and inflammation through nicotinic receptors,but enhances the proliferation and invasion of pancreatic tumor cells.This review focuses on the progression of cholinergic signaling and pancreatic diseases in recent years and reveals the role of cholinergic signaling in pancreatic diseases.

Diagnostic value of elevated serum carbohydrate antigen 125 level in sarcoidosis

BACKGROUND Sarcoidosis is a multisystem disorder with unknown etiology, and it predominantly affects the lungs and intrathoracic lymph nodes. For patients with atypical clinical manifestations, the diagnosis of sarcoidosis is difficult and specific biomarkers may play an important role in assisting diagnosis. Previous research has demonstrated a correlation between sarcoidosis and increased carbohydrate antigen 125(CA125), but remains a lack of large cohort studies to validate this observation.AIM To compare serum CA125 levels in sarcoidosis patients and healthy controls, and explore whether CA125 can be used as a biomarker for the diagnosis of sarcoidosis.METHODS In this study, the serum CA125 levels were measured by enzyme-linked immunosorbent assay in 108 consecutive sarcoidosis patients between June 2016 and December 2020(31 males, 77 females;age at diagnosis 49.69 ± 9.10 years) and 112 healthy subjects. Data on the C-reactive protein, erythrocyte sedimentation rate, and angiotensin-converting enzyme were also collected. The association of serum CA125 levels with clinical, radiological, and respiratory functional characteristics was analyzed between patient groups with CA125 ≤ 35 U/mL or CA125 >35 U/mL.RESULTS We found that serum CA125 levels were higher in sarcoidosis patients compared to healthy controls(median: 44.78 vs 19.11 U/mL, P < 0.001). The area under the receiver operator characteristic was 0.9833(95%CI: 0.9717-0.9949), and the best cutoff point was 32.33 U/mL. The elevated serum CA125 was notably associated with the percentage of predicted forced vital capacity(FVC%) and neutrophil-to-lymphocyte ratio(P =0.043 and P = 0.038, respectively) in sarcoidosis patients. Multivariate analysis revealed that FVC%was a statistically notable predictor of elevated serum CA125(P = 0.029). Also, our research revealed that compared to patients with Stage I of radiology classification, patients with Stage Ⅱ and Ⅲ showed a higher concentration of serum CA125(46.16 ± 8.32 vs 41.00 ± 6.04 U/mL, P =0.005, and 47.92 ± 10.10 vs 41.00 ± 6.04 U/mL, P = 0.002, respectively).CONCLUSION Serum CA125 was highly increased in sarcoidosis patients and showed high efficiency for noninvasive diagnosis of the disease. In addition, abnormally elevated serum CA125 was correlated with pulmonary function and radiological Scadding’s classification of sarcoidosis.

Identification of necroptosis-related lncRNAs for prognosis prediction and screening of potential drugs in patients with colorectal cancer

BACKGROUND Tumor recurrence and metastasis lead to a poor prognosis in colorectal cancer(CRC).Necroptosis is closely related to the tumor microenvironment(TME)and affects tumor recurrence and metastasis.We aimed to stratify CRC patients according to necroptosis-related long noncoding RNAs(lncRNAs),which can be used to not only evaluate prognosis and improve precision medicine in clinical practice but also screen potential immunotherapy drugs.AIM To stratify CRC patients according to necroptosis-related lncRNAs(NRLs),which can be used to not only evaluate prognosis and improve precision medicine in clinical practice but also screen potential immunotherapy drugs.METHODS LncRNA expression profiles were collected from The Cancer Genome Atlas.NRLs were identified by coexpression analysis.Cox regression analysis identified a NRL signature.Then,the value of this signature was comprehensively and multidimensionally evaluated,and its reliability for CRC prognosis prediction was assessed with clinical CRC data and compared with that of six other lncRNA were also performed according to the risk score(RS)of the signature.RESULTS An 8-lncRNA signature significantly associated with overall survival(OS)was constructed,and its reliability was validated with clinical CRC data.Most of the areas under the receiver operating characteristic curves(AUCs)values for 1-,3-and 5-year OS for this signature were higher than those for the other six lncRNA signatures.OS,disease-specific survival and the progression-free interval were all significantly poorer in the high-risk group.The RS of the signature showed good concordance with the predicted prognosis,with AUCs for 1-,3-and 5-year OS of 0.79,0.81 and 0.77,respectively.Additionally,the calibration plots for this signature combined with clinical factors showed that this combination could effectively improve the ability to predict OS.The RS was correlated with tumor stage,lymph node metastasis and distant metastasis.Most of the enriched Kyoto Encyclopedia of Genes and Genomes and Gene Ontology terms were tumor metastasis-related pathways in the high-risk group;these patients showed greater infiltration of immunosuppressive cells,such as cancer-associated fibroblasts,hematopoietic stem cells and M2 macrophages,but less infiltration of infiltrating antitumor effector immune cells,such as cluster of differentiation 8+T cells and regulatory T cells(Tregs).We explored additional potential immune checkpoint genes and potential immunotherapeutic and chemotherapeutic drugs with relatively low IC_(50) values.CONCLUSION We identified an NRL signature with strong fidelity that could stably predict prognosis and might be an indicator of the TME of CRC.Furthermore,additional potential immunotherapeutic and chemotherapeutic drugs were explored.

Magnetic field-enhanced photoelectrochemical water splitting of Co_(3)O_(4)/TiO_(2)for efficient oxygen evolution

Effective separation of photogenerated carriers plays a vital role in governing the efficiency of photo-electrocatalytic reactions.However,the advancement in enhancing the intrinsic carrier separation efficiency of semiconductors has shown limited progress.Herein,we reported the use of a magnetic field to improve the photoelectrochemical water splitting of a magnetic Co_(3)O_(4)/TiO_(2)photoanode by boosting the photogenerated carrier separation efficiency.In the presence of the magnetic field,oxygen evolution reaction occurs with a high photocurrent density of 0.86 mA cm^(−2)at 1.23 V versus VRHE,and an applied bias photon-to-current efficiency of 0.342%at 0.61 VRHE.Moreover,the photoanode maintains its oxygen evolution reaction for more than 400 h with photocurrent decays by ca.10%.Observations made in this effort show that the enhancement of photo-electrocatalytic efficiency by a magnetic field is a consequence of the effect of the Lorentz force generated by the magnetic field on photogenerated carriers and ions near the Co_(3)O_(4)/TiO_(2)photoanode,which improves the carrier separation efficiency and the bubble release rate.The results suggest that manipulating photoelectrode carriers by using a magnetic field is a promising strategy to design high-performance photoelectrochemical for water splitting.