Clinicopathological significance and immunotherapeutic outcome of claudin 18.2 expression in advanced gastric cancer:A retrospective study

Objective: Immunotherapeutic outcomes and clinical characteristics of claudin 18 isoform 2 positive(CLDN18.2-positive) gastric cancer(GC) vary in different clinical studies, making it difficult to optimize antiCLDN18.2 therapy. We conducted a retrospective analysis to explore the association of CLDN18.2 expression with clinicopathological characteristics and immunotherapeutic outcomes in GC.Methods: A total of 536 advanced GC patients from 2019 to 2021 in the CT041-CG4006 and CT041-ST-01clinical trials were included in the analysis. CLDN18.2 expression on ≥40% of tumor cells(2+, 40%) and CLDN18.2 expression on ≥70% of tumor cells(2+, 70%) were considered the two levels of positively expressed GC. The clinicopathological characteristics and immunotherapy outcomes of GC patients were analyzed according to CLDN18.2 expression status.Results: CLDN18.2 was expressed in 57.6%(cut-off: 2+, 40%) and 48.9%(cut-off: 2+, 70%) of patients.Programmed death-ligand 1(PD-L1) and CLDN18.2 were co-expressed in 19.8% [combined positive score(CPS)≥1, CLDN18.2(cut-off: 2+, 40%)] and 17.2% [CPS≥5, CLDN18.2(cut-off: 2+, 70%)] of patients.CLDN18.2 expression positively correlated with younger age, female sex, non-gastroesophageal junction(nonGEJ), and diffuse phenotype(P<0.001). HER2 and PD-L1 expression were significantly lower in CLDN18.2-positive GC(both P<0.05). Uterine adnexa metastasis(P<0.001) was more frequent and liver metastasis(P<0.001)was less common in CLDN18.2-positive GC. Overall survival and immunotherapy-related progression-free survival(ir PFS) were inferior in the CLDN18.2-positive group.Conclusions: CLDN18.2-positive GC is associated with poor prognosis and worse immunotherapeutic outcomes. The combination of anti-CLDN18.2 therapy, anti-PD-L1/PD-1 therapy, and chemotherapy for GC requires further investigation.

In Search of Regulators of <i>LeSPL-CNR</i>by South-Western Blotting and Yeast One-Hybrid Library Screening System

LeSPL-CNR is a crucial transcription factor for fruit ripening of Solanum lycopersicum. The cnr (colorless non-ripening) epimutation resulted from hypermethylation in a 286 bp region of LeSPL-CNR promoter inhibits normal fruit ripening. In present study, potential regulators of LeSPL-CNR, which could bind to the specific 286 bp region, were screened via south-western blotting and yeast one-hybrid (Y1H) library screening system. Results indicated that a total of 13 and 19 candidate proteins were acquired respectively, and both ribulose-1,5-bisphosphate carboxylase/oxygenase and 40S ribosomal protein were identified by two methods. These would provide some information for revealing roles of DNA methylation and the regulatory mechanism for LeSPL-CNR.

A Study of the Major Pathogens Causing Fruit Rots of Apple in Shelf Life in Hangzhou, Zhejiang Province, China

Major pathogens causing fruit rots of apple in shelf life in Hangzhou, a city in east China, were identified by rDNA-ITS analysis. Their pathogenicities and stress tolerances were compared as well. Combining with disease symptoms, colonial phenotypes and mycelial microscopic morphology, the fungi were determined as Penicillium expansum, Botrytis cinerea, Botryosphaeria dothidea, Diaporthe phaseolorum, Alternaria alternata and Fusarium acuminatum, respectively. Among them, B. cinerea and B. dothidea showed a higher pathogenicity;B. cinerea and D. phaseolorum were hardly affected by the temperature at a range of 15°C and 25°C;B. cinerea has the highest resistant to Thiabendazole and D. phaseolorum displayed the strongest resistance to Imazalil;and P. expansum was most sensitive to ultraviolet light radiation. The results provide some useful information that helps to combine conventional and alternative control strategies to minimize apple postharvest losses in shelf life.

NOMA-Based Spectrum Sensing for Satellite-Terrestrial Communication

With the continuous development of wireless communication technology,the number of access devices continues to soar,which poses a grate challenge to the already scarce spectrum resources.Meanwhile,6G will be an era of air-space-terrestrial-sea integration,and satellite spectrum resources are also very tight in the context of giant constellations.In this paper,we propose a Non-Orthogonal Multiple Access(NOMA)based spectrum sensing scheme for the future satellite-terrestrial communication scenarios,and design the transceiver from uplink and downlink scenarios,respectively.In order to better identify the user's transmission status,we obtain the feature values of each user through feature detection to make decision.We combine these two technologies to design the transceiver architecture and deduce the threshold value of feature detection in the satellite-terrestrial communication scenario.Simulations are performed in each scenario,and the results illustrate that the proposed scheme combining NOMA and spectrum sensing can greatly improve the throughput with a similar detection probability as Orthogonal Multiple Access(OMA).

The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype,promoting a favorable response to anti-PD-1 therapy via NLRP3 activation

The main challenges in the use of immune checkpoint inhibitors(ICIs)are ascribed to the immunosuppressive tumor microenvironment and the lack of sufficient infiltration of activated CD8+T cells.Transforming the tumor microenvironment(TME)from“cold”to“hot”and thus more likely to potentiate the effects of ICIs is a promising strategy for cancer treatment.We found that the selective BCL-2 inhibitor APG-2575 can enhance the antitumor efficacy of anti-PD-1 therapy in syngeneic and humanized CD34+mouse models.Using single-cell RNA sequencing,we found that APG-2575 polarized M2-like immunosuppressive macrophages toward the M1-like immunostimulatory phenotype with increased CCL5 and CXCL10 secretion,restoring T-cell function and promoting a favorable immunotherapy response.Mechanistically,we demonstrated that APG-2575 directly binds to NF-κB p65 to activate NLRP3 signaling,thereby mediating macrophage repolarization and the activation of proinflammatory caspases and subsequently increasing CCL5 and CXCL10 chemokine production.As a result,APG-2575-induced macrophage repolarization could remodel the tumor immune microenvironment,thus improving tumor immunosuppression and further enhancing antitumor T-cell immunity.Multiplex immunohistochemistry confirmed that patients with better immunotherapeutic efficacy had higher CD86,p-NF-κB p65 and NLRP3 levels,accompanied by lower CD206 expression on macrophages.Collectively,these data provide evidence that further study on APG-2575 in combination with immunotherapy for tumor treatment is required.

Environmental Information-Aided Electromagnetic Propagation Testbed for Maritime Communication

Maritime channel modeling can be affected by some key time-varying environmental factors.The ducting effect is one of the thorniest factors since it causes anomalous propagation enhancement and severe co-channel interference.Moreover,the atmospheric attenuation is much more severe in the ocean environment,resulting in shorter coverage distance and more link outage.In this paper,we propose an environmental information-aided electromagnetic propagation testbed.It is based on complex refractivity estimation and improved parabolic equation propagation model,taking into account both ducting effect and atmospheric attenuation.A large-scale temporal and spatial propagation measurement was conducted with meteorological acquisition.We consider practical path loss and ducting conditions to verify the testbed feasibility in these long-distance radio links.The simulation results are in good agreement with the measured data,which further reveal the basic temporal and spatial distribution of ducting effect at 3.5 GHz band.

Transformer 2β regulates the alternative splicing of cell cycle regulatory genes to promote the malignant phenotype of ovarian cancer

Late-stage ovarian cancer(OC)has a poor prognosis and a high metastasis rate,but the underlying molecular mechanism is unclear.RNA binding proteins(RBPs)play important roles in posttranscriptional regulation in the contexts of neoplasia and tumor metastasis.In this study,we explored the molecular functions of a canonical RBP,Transformer 2βhomolog(TRA2B),in cancer cells.TRA2B knockdown in HeLa cells and subsequent wholetranscriptome RNA sequencing(RNA-seq)analysis revealed the TRA2B-regulated alternative splicing(AS)profile.We disrupted TRA2B expression in epithelial OC cells and performed a series of experiments to confirm the resulting effects on OC cell proliferation,apoptosis and invasion.TRA2B-regulated AS was tightly associated with the mitotic cell cycle,apoptosis and several cancer pathways.Moreover,the expression of hundreds of genes was regulated by TRA2B,and these genes were enriched in the functions of cell proliferation,cell adhesion and angiogenesis,which are related to the malignant phenotype of OC.By integrating the alternatively spliced and differentially expressed genes,we found that AS events and gene expression were regulated independently.We then explored and validated the oncogenic functions of TRA2B by knocking down its expression in OC cells.The high TRA2B expression was associated with poor prognosis in patients with OC.In ovarian tissue,TRA2B expression showed a gradual increasing trend with increasing malignancy.We demonstrated the important roles of TRA2B in ovarian neoplasia and aggressive OC behaviors and identified the underlying molecular mechanisms,facilitating the targeted treatment of OC.

Atomistic insights into early stage corrosion of bcc Fe surfaces in oxygen dissolved liquid lead-bismuth eutectic(LBE-O)

Classical molecular dynamics simulations with global neural network machine learning potential are used to study early stage oxidation and dissolution behaviors of bcc Fe surfaces contacting with stagnant oxygen dissolved liquid leadbismuth eutectic(LBE-O).Both static and dynamic simulation results indicate that the early stage oxidation and dissolution behaviors of bcc Fe show strong orientation dependence under the liquid LBE environments,which may explain the experimental observations of uneven interface between iron-based materials and liquid LBE.Our investigations show that it is the delicate balance between the oxide growth and metal dissolution that leads to the observed corrosion anisotropy for bcc Fe contacting with liquid LBE-O.

单纯瓣膜置换术后机械通气时间延长的危险因素分析以及对临床预后的影响

目的探究单纯瓣膜置换(HVPI)术后机械通气时间延长(PMV)的发生率、危险因素以及对临床预后的影响。方法回顾性分析该院心胸外科2013年度的HVPI的400例患者。记录术前、术中以及术后等多种变量,进行单因素和多因素分析。呼吸机时间延长定义为术后呼吸机应用时间>24 h。结果 PMV患者87例(21.8%)。单因素分析发现非PMV组(A组)与PMV组(B组)患者在总胆红素水平、心功能Ⅲ~Ⅳ级、左室舒张末径、左室射血分数、转机时间、手术当天引流量、血红蛋白、血清肌酐、血糖、乳酸等方面,差异有统计学意义(P<0.05)。多因素分析发现LVEF>50%(OR=0.051,95%CI:0.005~0.541,P=0.014)是避免术后PMV的保护因素,而转机时间>120 min(OR=2.144,95%CI:1.061~4.335,P=0.034)、术后24 h肌酐>133μmol/L(OR=2.979,95%CI:1.463~6.069,P=0.003)和乳酸>5 mmol/L(OR=4.379,95%CI:2.115~9.067,P=0.000)是导致术后PMV的危险因素。术后PMV患者组患者术后死亡率(OR=8.0,95%CI:1.4~44.3,P=0.019)和ICU>2 d(OR=9.4,95%CI:5.4~16.3,P=0.000)的风险较对照组增加。结论 HVPI术后PMV与左心收缩功能、转机时间、术后早期肌酐和乳酸水平等多因素相关,PMV可导致术后死亡率增加和ICU滞留时间延长。

经皮肾镜联合电子肾盂镜或胆道镜与软镜治疗4cm内鹿角形结石的对比研究

目的探讨经皮肾镜联合电子肾盂镜或胆道镜与软镜处理鹿角形肾结石的安全性及有效性。方法回顾性分析2013年12月-2018年12月该院203例4 cm内鹿角形肾结石患者的临床资料,包括电子肾盂镜或胆道镜协同经皮肾镜的双镜联合组(n=122)和单纯输尿管软镜碎石取石术(RIRS)治疗组(n=81)。统计两组患者年龄、性别、结石大小和体重指数(BMI)等基线数据,进而对组间围术期数据进行对比分析。结果两组患者手术时间、并发症发生率和住院费用等比较,差异均无统计学意义(P> 0.05)。但两组患者一期结石清除率、住院时间和第三方患者满意度等方面比较,差异均有统计学意义(P <0.05)。结论双镜联合技术治疗4 cm内鹿角形肾结石具有结石一期清除率高和患者满意度高等特点,而RIRS则具有术后恢复快的优势。

“双一流”建设背景下民族地区本科院校学风建设路径探析——以广西高校为例

在"双一流"建设的背景下,民族地区的本科院校需抓住发展机遇,在拔尖创新人才培养方面开展系统的学风建设工程,搭建科研、实践、活动、网络育人四个平台,为地方经济和社会发展提供人才保障,为院校"双一流"建设提供强有力的人才支撑。

改性三叶形聚乙烯醇纤维/环氧树脂复合材料的结构与性能

异形截面纤维大的比表面积有利于提高纤维与基体树脂间的界面结合,改善复合材料的强度和韧性。文中采用环氧氯丙烷对熔纺三叶形聚乙烯醇(PVA)纤维进行表面改性,通过模压成型首次制备了改性三叶形PVA纤维/环氧树脂复合材料。对比研究了改性前后三叶形PVA纤维表面结构和性能及对复合材料力学性能的影响。结果表明,改性后三叶形PVA纤维表面出现鳞状沟槽,粗糙度增加;纤维表面接枝了环氧官能团,与环氧预浸料的接触角减小,浸润性增加;表面接枝的环氧官能团参与了基体树脂的固化反应,单纤拔出力提高至3.61 N;改性三叶形PVA纤维/环氧复合材料的拉伸强度、弯曲强度和冲击强度分别为62.3 MPa,53.8 MPa和79.0 kJ/m^(2),比未改性三叶形PVA纤维/环氧复合材料分别提高了22.9%,134.9%和43.1%。

Advances of supercritical fluid chromatography in lipid profiling

Supercritical fluid chromatography(SFC) meets with great favor due to its high efficiency, low organic solvent consumption, and the specialty for the identification of the isomeric species. This review describes the advances of SFC in targeted and untargeted lipid profiling. The advancement of the SFC instruments and the stationary phases are summarized. Typical applications of SFC to the targeted and untargeted lipid profiling are discussed in detail. Moreover, the perspectives of SFC in the lipid profiling are also proposed. As a useful and promising tool for investigating lipids in vitro and in vivo, SFC will predictably obtain further development.

Surface modification of Ti-49.8at%Ni alloy by Ti ion implantation: phase transformation, corrosion, and cell behavior

The Ti-49.8at%Ni alloy was modified by Ti ion implantation to improve its corrosion resistance and biocompatibility. The chemical composition and morphologies of the Ti Ni alloy surface were determined using atomic force microscopy(AFM), auger electron spectroscopy(AES), and X-ray photoelectron spectroscopy(XPS). The results revealed that Ti ion implantation caused the reduction of Ni concentration and the formation of a Ti O2 nano-film on the Ti Ni alloy. The phase transformation temperatures of the Ti–Ti Ni alloy remained almost invariable after Ti ion implantation. Electrochemical tests indicated that the corrosion resistance of Ti Ni increased after Ti ion implantation. Moreover, the Ni ion release rate in 0.9% Na Cl solution for the Ti Ni alloy remarkably decreased due to the barrier effect of the Ti O2 nano-film. The cell proliferation behavior on Ti-implanted Ti Ni was better than that on the untreated Ti Ni after cell culture for 1 d and 3 d.

Establishment and evaluation of operation function model for cascade hydropower station

Toward solving the actual operation problems of cascade hydropower stations under hydrologic uncertainty, this paper presents the process of extraction of statistical characteristics from long-term optimal cascade operation, and proposes a monthly operation function algorithm for the actual operation of cascade hydropower stations through the identification, processing, and screening of available information during long-term optimal operation. Applying the operation function to the cascade hydropower stations on the Jinshajiang-Yangtze River system, the modeled long-term electric generation is shown to have high precision and provide benefits. Through comparison with optimal operation, the simulation results show that the operation function proposed retains the characteristics of optimal operation. Also, the inadequacies and attribution of the algorithm are discussed based on case study, providing decision support and reference information for research on large-scale cascade operation work.

Biodegrading Wheat Bran with Agaricus blazei and Its Effects on Intestinal Development Identified with Mice

Agaricus blazei Murill is a well known edible/medicinal mushroom used for immune-nutrient food therapies.The biodegradation of different substrates with this fungus may result in different metabolites and degraded compounds,which may enrich the function of the food therapies.In this study,soluble compounds from the culture of A.blazei grown in liquid media with whole wheat bran and its water filtrate,respectively,were compared.Total soluble sugar,arabinoxylan,protein,and amino acids were significantly higher in the fungal culture resulted from the medium with whole wheat bran （43.54,1.56,0.59,and 2.19 mg mL^-1,respectively） than that from the medium with the bran filtrate （17.28,0.37,0.13,and 1.13 mg mL^-1,respectively）.The biodegraded wheat bran with cultured mycelia was fed to Mus musculus Linnaeus as supplementation or as dietary fiber exclusive ingredient.As non-specific food therapies,feeding effects on mice intestinal development were indicated indirectly in growth performance,intestinal absorption and serum parameters.Compared to feeding uncultured wheat bran,feeding mice with culture mixes of A.blazei resulted in remarkably increase in villus height and villus height/crypt depth ratio,which were increased by 25.4 and 31.0%,respectively,when applied as supplementation,and by 44.3 and 43.4%,respectively,when applied as dietary fiber.These increases are concomitant with the higher level of D-xylose in blood serum about 16.9 and 29.2% as supplementation and dietary fiber,respectively.The results implying that culturing A.blazei with whole wheat bran enhanced extracellular metabolism of the fungus and extensive degradation of wheat bran insoluble fibrous compounds.Furthermore,feeding the culture mix including metabolites and degraded wheat bran improved intestinal villus development,proving the nutritional benefits of the A.blazei mycelial cultures.

Effect of An Atmospheric Plasma Jet on the Differentiation of Melanoblast Progenitor

Objective Melanoblasts are the cell source of regeneration for pigment restoration.The ability to differentiate into mature melanocytes is the essential feature of melanoblasts in depigmentation diseases.Cold atmospheric plasma is an ionized gas with near-room temperature and highly reactive species that has been shown to induce stem cell differentiation.The aim of the study was to explore the effect of cold atmospheric plasma on the differentiation of melanoblast progenitor cells.Methods In this study,melanoblasts were exposed to the plasma jet and the cell morphology was observed.The cell cycle and cell proliferation were detected.Furthermore,the cell immunofluorescence and the detection of melanin particle and nitric oxide were carried out to investigate the differentiation of melanoblast progenitor cells.Results Cells that were treated with the plasma had longer and more synaptic structures,and the G1 phase of cell cycle was prolonged in the treated group.More melanin synthesis-related proteins and melanin particles were produced after plasma treatment.Nitric oxide was one of the active components generated by the plasma jet,and the nitric oxide content in the cell culture medium of the treated group increased.Conclusion These results indicate that an increase in nitric oxide production caused by a plasma jet can promote cell differentiation.The application of plasma provides an innovative strategy for the treatment of depigmentation diseases.

Weight Based Channel Selection Towards 5G in the Unlicensed Spectrum

The growth of the wireless and mobile communication data traffic has brought severe challenges to the present telecommu- nication systems. To meet the ever-increasing mobile traffic demand in the next 5th generation （SG） communication systems, deploying 5G in the unlicensed spectrum （SG-U）, has been regarded as a promising technology. The Third Generation Partnership Project （3GPP） has specified the standardization of the Li- censed Assisted Access （LAA） and its extension enhanced LAA （eLAA）, to opportunistically transmit in the unlicensed spectrum. The LAA/eLAA systems share unlicensed spectrum resource with other networks, e.g., the Wi-Fi systems. In this article, we analyze the coexistence between the eLAA and the Wi-Fi systems in the unlicensed spectrum. We firstly establish the system model where the eLAA coexists with the Wi-Fi systems. Then, we theoretically derive and figure out the unfairness in the multi-channel occupancy rate between the eLAA and the Wi-Fi systems. After that, we propose a weight based channel selection method to improve the fairness of the coexistence. The numerical results demonstrate that by avoiding contentions and declining collisions, our method not only enhances the fairness, but also improves the overall unlicensed spectrum usage rate.

间充质干细胞在脓毒症的应用研究进展

脓毒症是危急重症医学常年面临的重要问题,是危及危重病患者生命的主要原因之一,且患病率不断增加,但目前尚无有效的治疗方法。近年来间充质干细胞(MSCs)因其免疫调节、抗菌、调节器官衰竭、抗凋亡、抗炎症小体等特性应用于治疗脓毒症的临床前研究,其特性与脓毒症的发病机制有较多联系,该文阐述MSCs治疗脓毒症的相关知识以及目前在体内外治疗脓毒症的相关研究,以探讨MSCs治疗脓毒症新思路和未来的努力方向。

Histone demethylase JMJD3 downregulation protects against aberrant force-induced osteoarthritis through epigenetic control of NR4A1

Osteoarthritis(OA)is a prevalent joint disease with no effective treatment strategies.Aberrant mechanical stimuli was demonstrated to be an essential factor for OA pathogenesis.Although multiple studies have detected potential regulatory mechanisms underlying OA and have concentrated on developing novel treatment strategies,the epigenetic control of OA remains unclear.Histone demethylase JMJD3 has been reported to mediate multiple physiological and pathological processes,including cell differentiation,proliferation,autophagy,and apoptosis.However,the regulation of JMJD3 in aberrant force-related OA and its mediatory effect on disease progression are still unknown.In this work,we confirmed the upregulation of JMJD3 in aberrant forceinduced cartilage injury in vitro and in vivo.Functionally,inhibition of JMJD3 by its inhibitor,GSK-J4,or downregulation of JMJD3 by adenovirus infection of sh-JMJD3 could alleviate the aberrant force-induced chondrocyte injury.Mechanistic investigation illustrated that aberrant force induces JMJD3 expression and then demethylates H3K27me3 at the NR4A1 promoter to promote its expression.Further experiments indicated that NR4A1 can regulate chondrocyte apoptosis,cartilage degeneration,extracellular matrix degradation,and inflammatory responses.In vivo,anterior cruciate ligament transection(ACLT)was performed to construct an OA model,and the therapeutic effect of GSK-J4 was validated.More importantly,we adopted a peptide-si RNA nanoplatform to deliver si-JMJD3 into articular cartilage,and the severity of joint degeneration was remarkably mitigated.Taken together,our findings demonstrated that JMJD3 is flow-responsive and epigenetically regulates OA progression.Our work provides evidences for JMJD3 inhibition as an innovative epigenetic therapy approach for joint diseases by utilizing p5RHH-si RNA nanocomplexes.