VEGF, HIF-1α, and Metabolic Indicators in Esophageal Squamous Cell Carcinoma

Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinoma(ESCC).Methods:Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group.Sixty normal healthy patients from the same period were chosen as the control group.Their serum samples and tissue samples were collected.Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission.RT-PCR was utilized to detect the expression of VEGF and HIF-1αin ESCC tissues.Results:The expression of VEGF and HIF-1αin the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ(Tis)group,T1+T2 group,and control group.Furthermore,the expression of HIF-1αwas found to be related to the expression of VEGF,showing a significant correlation between the quantities.Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group(P<0.05).Conclusion:Metabolic indicators are associated with the onset of ESCC in patients.Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors.The expression of VEGF and HIF-1αin ESCC tissues significantly correlates with the tumor stage,providing a new reference for the diagnosis and treatment of ESCC.

The Sustainable Development Pathway of the Biomedical Industry Based on Environmental,Social,and Governance(ESG)Concepts

There is a growing global awareness of environmental,social,and governance(ESG)concerns.The biopharmaceutical industry is an important field that affects human health and well-being,and its sustainable development is now the industry’s focus.Based on the current state of the green development of China’s biopharmaceutical industry,the article proposes suggestions and paths for promoting the industry to better fulfill its social responsibilities and protect the environment while pursuing economic benefits.By doing so,the industry can make a greater contribution to global public health and become an important factor in promoting human health and social prosperity.

Evaluation of the Application Effect of Enteral and Parenteral Nutrition Therapy Combined with a Health Belief Education Model in Patients with Inflammatory Bowel Disease

Objective:To evaluate the application effect of enteral and parenteral nutrition therapy combined with a health belief education model in patients with inflammatory bowel disease.Methods:80 patients with inflammatory bowel disease admitted to the Shanghai Zhangjiang Institute of Medical Innovation were chosen.This study was carried out from August 2022 to October 2023.The patients were randomly divided into a study group(40 cases)and a control group(40 cases).The treatment plan for the control group was the conventional treatment model,while the treatment plan for the study group was to provide enteral and parenteral nutrition therapy combined with a health belief education model based on the control group.The efficacy of both groups was compared.Results:In the study group,the therapeutic effect for 31 patients(77.50%)was markedly effective and 7 was effective(17.50%),accounting for 95.0%of the total,which was higher than the control group at 80.0%(P<0.05).The relief time of relevant symptoms in the study group was shorter than that of the control group(P<0.05).Before treatment,there were no differences in the high-sensitivity C-reactive protein(hs-CRP),interleukin 10(IL-10),and tumor necrosis factor-α(TNF-α)between both groups(P>0.05).After treatment,the levels of inflammatory factors in the study group(hs-CRP(8.02±1.13)mg/L,IL-10(9.24±1.25)pg/mL,and TNF-α(7.19±1.04)ng/L)were lower than those in the control group(P<0.05).Conclusion:Enteral and parenteral nutritional therapy combined with a health belief education model showed significant efficacy in inflammatory bowel disease patients.Patient symptoms were relieved and inflammatory reactions were reduced.This method is worthy of popularization.

A quick and reliable image-based AI algorithm for evaluating cellular senescence of gastric organoids

Objective:Organoids are a powerful tool with broad application prospects in biomedicine.Notably,they provide alternatives to animal models for testing potential drugs before clinical trials.However,the number of passages for which organoids maintain cellular vitality ex vivo remains unclear.Methods:Herein,we constructed 55 gastric organoids from 35 individuals,serially passaged the organoids,and captured microscopic images for phenotypic evaluation.Senescence-associatedβ-galactosidase(SA-β-Gal),cell diameter in suspension,and gene expression reflecting cell cycle regulation were examined.The YOLOv3 object detection algorithm integrated with a convolutional block attention module(CBAM)was used to evaluate organoid vitality.Results:SA-β-Gal staining intensity;single-cell diameter;and expression of p15,p16,p21,CCNA2,CCNE2,and LMNB1 reflected the progression of aging in organoids during passaging.The CBAM-YOLOv3 algorithm precisely evaluated aging organoids on the basis of organoid average diameter,organoid number,and number×diameter,and the findings positively correlated with SA-β-Gal staining and single-cell diameter.Organoids derived from normal gastric mucosa had limited passaging ability(passages 1–5),before aging,whereas tumor organoids showed unlimited passaging potential for more than 45 passages(511 days)without showing clear senescence.Conclusions:Given the lack of indicators for evaluating organoid growth status,we established a reliable approach for integrated analysis of phenotypic parameters that uses an artificial intelligence algorithm to indicate organoid vitality.This method enables precise evaluation of organoid status in biomedical studies and monitoring of living biobanks.

A highly degradable Mg-Al-Ca alloy with superior anti-tumor efficacy

Molecule hydrogen(H_(2)) has been used to suppress tumor growth. To employ the H_(2) therapy, it is necessary to use a proper agent for continuous generation of H_(2). As a biodegradable metal, magnesium(Mg) generates H_(2) in an aqueous environment, but the H_(2) release rate is still too low. Here, we design a Mg-Al-Ca(AX) alloy that degrades very rapidly due to the presence of a secondary phase Al_(2)Ca. Having a reduction potential much higher than Mg and any other Mg-based secondary phases, Al_(2)Ca accelerates the corrosion of the Mg matrix by a micro-galvanic process. Al_(2)Ca also enhances the strength and ductility of the AX alloy. AX alloy rods show better anti-tumor efficacy than pure Mg rods in vivo. Moreover, implanted AX alloy rods can be heated under an alternating magnetic field to suppress large-size tumors.This work suggests that the H_(2) therapy using highly degradable Mg alloys may provide an effective cancer treatment.

Coxsackievirus A6 was the most common enterovirus serotype causing hand,foot,and mouth disease in Shiyan City,central China

BACKGROUND Hand,foot,and mouth disease(HFMD)has become one of the most common infectious diseases in China.Before 2016,the primary causal serotypes were enterovirus A71(EV-A71)and coxsackievirus A16(CV-A16).Following the introduction of EV-A71 vaccines in China since 2016,the situation could change.CV-A6 has recently replaced EV-A71 and CV-A16 in some areas of China.However,the epidemiological characteristics of central China remain unknown.AIM To investigate the clinical symptoms and pathogen spectrum of HFMD in Shiyan City,central China,in recent years.METHODS The epidemiological,clinical,and laboratory data from HFMD cases reported to the Shiyan Center for Disease Control and Prevention between January 2016 and December 2020 were analyzed.196 throat swab specimens were collected from hospitalized HFMD patients between January 2018 and December 2020.To detect and genotype enteroviruses,real-time reverse transcription-polymerase chain reaction and sequencing of the 5'-untranslated region were used.In Shiyan,168 laboratory-confirmed HFMD cases were studied using a logistic regression model to determine the effect of predominant enterovirus serotypes.Based on the logistic regression model,the least absolute shrinkage and selection operator model was used to analyze the correlation between CV-A6 infection and various clinical characteristics in HFMD patients in Shiyan.RESULTS From 2016 to 2020,35840 HFMD cases were reported in Shiyan.The number of cases decreased by 48.4%from 2016 to 2017.Approximately 1.58-fold increases were found in 2018 and 2019 when compared to the previous year,respectively.In 2020,a decrease of about 85.5%was reported when compared to 2019.The most common serotypes shifted from EV-A71 and CV-A16(about 60%-80%in 2016 and 2018)to others(more than 80.0%in 2017,2019,and 2020).EV-A71 lost its dominance in 2017 in Shiyan.Among 196 confirmed HFMD cases,85.7%tested positive for enterovirus,with CV-A6 being the most common serotype(121/168,72.0%).The positive rates for CV-A16 and CVA10 were 4.8%and 3.0%,respectively.There was no EV-A71 discovered.Infection with CV-A6 was linked to fever,myocardial damage,increased creatine kinase MB isoenzyme,and lactate dehydrogenase levels.CONCLUSION CV-A6 was the most common enterovirus serotype in Shiyan City,replacing EV-A71 and CV-A16 as the HFMD pathogen.Developing vaccines against CV-A6 or multiple pathogens,as well as rising CV-A6 surveillance,will help prevent HFMD in central China.

In-situ monitoring of dynamic behavior of catalyst materials and reaction intermediates in semiconductor catalytic processes

Semiconductor photocatalysis, as a key part of solar energy utilization, has far-reaching implications for industrial, agricultural, and commercial development. Lack of understanding of the catalyst evolution and the reaction mechanism is a critical obstacle for designing efficient and stable photocatalysts. This review summarizes the recent progress of in-situ exploring the dynamic behavior of catalyst materials and reaction intermediates. Semiconductor photocatalytic processes and two major classes of in-situ techniques that include microscopic imaging and spectroscopic characterization are presented. Finally, problems and challenges in in-situ characterization are proposed, geared toward developing more advanced in-situ techniques and monitoring more accurate and realistic reaction processes, to guide designing advanced photocatalysts.

Synthesis,Crystal Structure and Biological Activity of(2,4-Dihydroxy-3,6-dimethoxyphenyl)-((1R,2S,3S,4R,7R)-7-isopropyl-5-methyl-3-phenylbicyclo[2.2.2]-oct-5-en-2-yl)methanone

The crystal structure of the natural terpene derivative（2,4-dihydroxy-3,6-dimethoxyphenyl）(（1 R,2 S,3 S,4 R,7 R）-7-isopropyl-5-methyl-3-phenylbicyclo[2.2.2]oct-5-en-2-yl)-methanone was determined by single-crystal X-ray diffraction method. The compound crystallizes in triclinic,space group P21/c with a = 16.1444（9）, b = 16.5294（9）, c = 19.7875（11） ?, V = 5280.4（5） ?3, Z = 4,Dc = 1.209 g/cm;, F（000） = 2064, μ（Cu Kα） = 0.675 mm-1, S = 1.069, R = 0.0520 and wR(I > 2σ（I）)= 0.1392. The spiro structure constructed by Diels-Alder reaction was highly symmetric. In addition,the title compound showed inhibitory activities against cancer cell line with varied potencies.

Synthesis,Configuration Judgment and Potentiation Activity of (2S,3S,E)-4-(3,4-Dihydroxybenzylidene)-3-(3,4-dihydroxyphenyl)-5-oxotetrahydrofuran-2-carboxylic Acid

The title compound（2S,3S,E）-4-（3,4-dihydroxybenzylidene）-3-（3,4-dihydroxyphenyl）-5-oxotetrahydrofuran-2-carboxylic acid was synthesized and the 2D structure was characterized by ^1H-NMR ^13C-NMR and LCMS. The absolute configuration was determined by single-crystal X-ray diffraction of the key intermediate（2S,3S,E）-ethyl 4-（3,4-dimethoxybenzylidene）-3-（3,4-dimethoxyphenyl）-5-oxotetrahydrofuran-2-carboxylate. The crystal belongs to tetragonal system, space group P41 with a = 13.0665（2）, b = 13.0665（2）, c = 13.4735（2）A, V = 2300.4（6） A^3, Z = 4, Dc = 1.278 g/cm^3, μ（CuKα） = 0.801 mm^-1, F（000） = 936, S = 1.050, R = 0.0364 and wR（I 〉 2σ（I）） = 0.1071. X-ray diffraction results showed that the molecular structure is stabilized totally by Van der Waals force. The antibacterial activity tests showed that the title compound possesses slight synergistic effect against MRSA and Acinetobacter baumanii.

β-Lactoglobulin stabilized lipid nanoparticles enhance oral absorption of insulin by slowing down lipolysis

Lipid-based nanocarriers have staged a remarkable comeback in the oral delivery of proteins and peptides, but delivery efficiency is compromised by lipolysis. β-Lactoglobulin(β-lg) stabilized lipid nanoparticles, including nanoemulsions(NE@β-lg) and nanocapsules(NC@β-lg), were developed to enhance the oral absorption of insulin by slowing down lipolysis due to the protection from β-lg. Cremophor EL stabilized nanoemulsions(NE@Cre-EL) were prepared and set as a control. The lipid nanoparticles produced mild and sustained hypoglycemic effects, amounting to oral bioavailability of 3.0% ± 0.3%, 7.0% ± 1.1%, and7.7% ± 0.8% for NE@Cre-EL, NE@β-lg, and NC@β-lg, respectively. Aggregation-caused quenching(ACQ)probes enabled the identification of intact nanoparticles, which were used to investigate the in vivo and intracellular fates of the lipid nanoparticles. In vitro digestion/lipolysis and ex vivo imaging confirmed delayed lipolysis from β-lg stabilized lipid nanoparticles. NC@β-lg was more resistant to intestinal lipolysis than NE@β-lg due to the Ca^(2+)-induced crosslinking. Live imaging revealed the transepithelial transport of intact nanoparticles and their accumulation in the liver. Cellular studies confirmed the uptake of intact nanoparticles. Slowing down lipolysis via food proteins represents a good strategy to enhance the oral absorption of lipid nanoparticles and thus co-formulated biomacromolecules.

Direct synthesis of unnatural amino acids and modifications of peptides via LADA strategy

Unnatural amino acids(UAAs)have broad applications in pharmaceutical sciences and biological studies.Current synthetic methods for UAAs mainly rely on asymmetric catalysis and often require several steps.There is a lack of direct and simple methods.To address this challenge,we designed the LADA(labeling-activation-desulfurization-addition)strategy:selective labeling and activation of cysteine residues,the photocatalytic desulfurization and the subsequent radical addition to alkenes.Although composed of two steps,it is one-pot synthesis and has advantages such as high functional group tolerance,biocompatible reaction condition,and retained stereochemistry.This highly efficient strategy was successfully applied in the direct synthesis of unnatural amino acids and modifications of peptides with more than 50 examples.

EHMT2 promotes tumorigenesis in GNAQ/11-mutant uveal melanoma via ARHGAP29-mediated RhoA pathway

Constitutive activation of GNAQ/11 is the initiative oncogenic event in uveal melanoma(UM).Direct targeting GNAQ/11 has yet to be proven feasible as they are vital for a plethora of cellular functions.In search of genetic vulnerability for UM,we found that inhibition of euchromatic histone lysine methyltransferase 2(EHMT2)expression or activity significantly reduced the proliferation and migration capacity of cancer cells.Notably,elevated expression of EHMT2 had been validated in UM samples.Furthermore,Kaplan-Meier survival analysis indicated high EHMT2 protein level was related to poor recurrence-free survival and a more advanced T stage.Chromatin immunoprecipitation sequencing analysis and the following mechanistic investigation showed that ARHGAP29 was a downstream target of EHMT2.Its transcription was suppressed by EHMT2 in a methyltransferasedependent pattern in GNAQ/11-mutant UM cells,leading to elevated RhoA activity.Rescuing constitutively active RhoA in UM cells lacking EHMT2 restored oncogenic phenotypes.Simultaneously blocking EHMT2 and GNAQ/11 signaling in vitro and in vivo showed a synergistic effect on UM growth,suggesting the driver role of these two key molecules.In summary,our study shows evidence for an epigenetic program of EHMT2 regulation that influences UM progression and indicates inhibiting EHMT2 and MEK/ERK simultaneously as a therapeutic strategy in GNAQ/11-mutant UM.

Sustainable thermal energy harvest for generating electricity

Electricity is the lifeblood of modern society.However,the predominant source of electricity generation still relies on non-renewable fossil fuels,whose combustion releases greenhouse gases contributing to global warming.The increasing demand for energy and escalating environmental concerns necessitate proactive measures to develop innovative green energy technologies capable of both cooling the Earth and generating electricity.Here,we look forward to an interdisciplinary power system integrating solar absorbers,radiative coolers,and thermoelectric generators.This system can simultaneously harvest thermal energy from the sun and from cold space,thereby transforming the challenges posed by global warming into opportunities for the production of clean electricity.We underscore recent advancements in this field and address key challenges while also exploring forward-looking opportunities in the foreseeable future.The proposed integrated energy technology achieves uninterrupted power supply through the unrestricted capture of thermal energy,offering a robust alternative pathway for next-generation sustainable energy technologies.

GLI1 and PTTG1 expression in colorectal carcinoma patients undergoing radical surgery and their correlation with lymph node metastasis

BACKGROUND Few studies have investigated the expression of GLI1 and PTTG1 in patients undergoing radical surgery for colorectal carcinoma(CRC)and their association with lymph node metastasis(LNM).Therefore,more relevant studies and analyses need to be conducted.AIM To explore GLI1 and PTTG1 expression in patients undergoing radical surgery for CRC and their correlation with LNM.METHODS This study selected 103 patients with CRC admitted to our hospital between April 2020 and April 2023.Sample specimens of CRC and adjacent tissues were collected to determine the positive rates and expression levels of GLI1 and PTTG1.The correlation of the two genes with patients’clinicopathological data(e.g.,LNM)was explored,and differences in GLI1 and PTTG1 expression between patients with LNM and those without were analyzed.Receiver operating characteristic(ROC)curves were plotted to evaluate the predictive potential of the two genes for LNM in patients with CRC.RESULTS Significantly higher positive rates and expression levels of GLI1 and PTTG1 wereobserved in CRC tissue samples compared with adjacent tissues.GLI1 and PTTG1 were strongly linked to LNM in patients undergoing radical surgery for CRC,with higher GLI1 and PTTG1 levels found in patients with LNM than in those without.The areas under the ROC curve of GLI1 and PTTG1 in assessing LNM in patients with CRC were 0.824 and 0.811,respectively.CONCLUSION GLI1 and PTTG1 expression was upregulated in patients undergoing radical surgery for CRC and are significantly related to LNM in these patients.Moreover,high GLI1 and PTTG1 expression can indicate LNM in patients with CRC undergoing radical surgery.The expression of both genes has certain diagnostic and therapeutic significance.

Protein amyloid aggregate:Structure and function

Protein amyloid aggregation has been widely observed to occur and plays impor-tant roles in both physiological processes and pathological diseases.Remarkably,amyloid aggregates assembled by native proteins gain a variety of different biolog-ical activities,which cannot be adopted by the unassembled protein alone.Thus,it is important to investigate the molecular basis of self-assembly of protein amyloid aggregates and how the aggregated protein structure determines its function.In the review,wefirstly introduce our structural knowledge on how different amyloid pro-teins undergo conformational transition and assemble into amyloid aggregate,with the main focus on amyloidfibril,which is the major species of amyloid aggregate.Then,we elaborate how different structures of amyloidfibrils enable them to fulfill highly diverse functions in either physiological or pathological condition.Further-more,we discuss the structural polymorph which is a very unique feature of amyloidfibril,and its implication in understanding the structure-function relationship of amy-loidfibrils.Finally,we point out the importance of applying and integrating new approaches for deepening the structure-function study of amyloidfibrils and high-light the potential of designing amyloidfibril-based functional bio-nanomaterials for application.

远程碳氢键活化用于平面手性的构建

Planar chirality is a fascinating type of chirality that is exploited in natural systems and also finds significant applications as chiral catalysts and functional materials.In particular,chiral ferrocenes represent one of the most extensively studied planar-chiral skeletons in asymmetric catalysis(Scheme 1a)[1].

Current research trends of nanomedicines

Owing to the inherent shortcomings of traditional therapeutic drugs in terms of inadequate therapeutic efficacy and toxicity in clinical treatment,nanomedicine designs have received widespread attention with significantly improved efficacy and reduced non-target side effects.Nanomedicines hold tremendous theranostic potential for treating,monitoring,diagnosing,and controlling various diseases and are attracting an unfathomable amount of input of research resources.Against the backdrop of an exponentially growing number of publications,it is imperative to help the audience get a panorama image of the research activities in the field of nanomedicines.Herein,this review elaborates on the development trends of nanomedicines,emerging nanocarriers,in vivo fate and safety of nanomedicines,and their extensive applications.Moreover,the potential challenges and the obstacles hindering the clinical translation of nanomedicines are also discussed.The elaboration on various aspects of the research trends of nanomedicines may help enlighten the readers and set the route for future endeavors.

PLGA-based implants for sustained delivery of peptides/proteins:Current status,challenge and perspectives

Peptide and protein drugs with therapeutic effects suffer from their short half-life and low stability,albeit their high efficiency and specificity.To overcome these demerits,long-acting drug delivery systems have been developed,wherein poly(lactic-co-glycolic acid)(PLGA)implants are most preferred owing to their excellent biodegradability and biocompatibility.Dozens of PLGA based products have been approved since1986,when the first product,named Decapeptyl R,successfully marched into market.To meet the increasing demand for delivering various peptides and proteins,different kinds of technologies have been developed for lab-scale fabrication or industrial manufacture.This review aims to introduce recent advances of PLGA implants,and give a brief summary of fundamental properties of PLGA,fabrication technologies of peptides/proteins-loaded PLGA implants as well as factors influencing the drug release processes.Moreover,challenges and future perspectives are also highlighted.

纤维电池助力可穿戴电子设备

The International Union of Pure and Applied Chemistry(IUPAC)released"fibre batteries"as one of the"2022 IUPAC Top Ten Emerging Technologies in the Field of Chemistry"on November 2022.Differing from conventional batteries that are generally bulky and rigid with poor wearability,fibre batteries are promising in wearable applications owing to the attractive features of being flexible and twistable,and can be woven into breathable fabrics to power various wearable devices[1–3].

LADA strategy for the synthesis of unnatural amino acids and direct modifications of peptides

Unnatural amino acids(UAAs)are important building blocks in organic synthesis and drug discovery.They are also frequently integrated into peptides or proteins for biological studies.However,the direct and simplified synthesis of UAAs remains a great challenge.At the same time,vast known peptide modifications are based on carbon-heteroatom bonds.There are no general methods for peptide modifications via the construction of C–C bonds.To address this challenge,herein we propose the LADA strategy,which is composed of two steps:the selective labeling and activation of cysteine residues,the desulfurization to generate carbon-centered radical and the radical addition to alkenes to build C–C bond.This one-pot protocol has obvious advantages such as good functional group tolerance,biocompatible reaction conditions,and retained stereochemistry.This strategy was successfully utilized for the synthesis of unnatural amino acids and direct modifications of peptides.