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Abstract Acute liver failure (ALF) is characterized by the rapidly progressive deterioration of hepatic function, which, without effective medical intervention, results in high mortality and morbidity. Here, using proteomic and transcriptomic analyses in murine ALF models, we found that the expression of multiple splicing factors was downregulated in ALF. Notably, we found that KH-type splicing regulatory protein (KHSRP) has a protective effect in ALF. Knockdown of KHSRP resulted in dramatic splicing defects, such as intron retention, and led to the exacerbation of liver injury in ALF. Moreover, we demonstrated that KHSRP directly interacts with splicing factor 3b subunit 1 (SF3B1) and enhances the binding of SF3B1 to the intronic branch sites, thereby promoting pre-mRNA splicing. Using splicing inhibitors, we found that Khsrp protects against ALF by regulating pre-mRNA splicing in vivo. Overall, our findings demonstrate that KHSRP is an important splicing activator and promotes the expression of genes associated with ALF progression by interacting with SF3B1; thus, KHSRP could be a possible target for therapeutic intervention in ALF.

Abstract Background This meta-analysis aimed to assess the safety and efficacy of robotic-assisted natural orifice specimen extraction surgery (NOSE) compared to traditional robotic transabdominal wall specimen retrieval surgery (TWSR) for colorectal cancer. Methods A systematic search was conducted in three electronic databases (PubMed, Web of Science and Embase) from inception to August 2023. Primary outcomes included postoperative complications, the number of lymph nodes harvested, overall survival and disease-free survival. Secondary outcomes included the postoperative visual analog scale (VAS) score, the additional use of analgesics, the restoration of gastrointestinal function, blood loss, the mean operation time, and length of postoperative hospital stay. Results In this meta-analysis, a total of 717 patients from 6 observational studies met the inclusion criteria. Compared with the TWSR group, the NOSE group had greater benefits in terms of overall postoperative complications [odds ratios (OR) 0.55; 95% confidence intervals (CI) = 0.34 to 0.89; P = 0.01, I 2 = 0%)], the number of lymph nodes harvested [weighted mean differences (WMD) = 1.18; 95% CI = 0.15 to 2.21; P = 0.02, I 2 = 0%)], the rate of wound infection (OR 0.17; 95% CI = 0.04 to 0.80; P = 0.02, I 2 = 0%), the passed flatus time (WMD = − 0.35 days; 95% CI = − 0.60 to − 0.10; P = 0.007, I 2 = 73%), the additional use of analgesics (OR 0.25; 95% CI = 0.15 to 0.40; P

To ensure the operational safety of nuclear power plants, we present a Quadruped Inspection Robot that can be used for many types of steam generators. Since the Inspection Robot relies on the Holding Modules to grip the tube-sheet, it can be regarded as a hybrid robot with variable configurations, switching between 4-RRR-RR, 3-RRR-RR, and two types of 2-RRR-RR, and the variable configurations bring a great challenge to dimensional synthesis. In this paper, the kinematic model of the Inspection Robot in multiple configurations is established, and the analytical solution is given. The workspace mapping is analyzed by the solution-space, and the workspace of multiple configurations is decomposed into the workspace of 2-RRR to reduce the analysis complexity, and the workspace calculation is simplified by using the envelope rings. The optimization problem of the manipulator is transformed into the calculation of the shortest contraction length of the swing leg. The switching performance of the Inspection Robot is evaluated by stride-length, turning-angle, and workspace overlap-ratio. The performance indexes are classified and transformed based on the proportions and variation trends of dimensional parameters to reduce the number of optimization objective functions, and Pareto optimal solutions are obtained using an intelligent optimization algorithm.

[Objective] The iron and steel industry is the largest carbon emitter in the field of energy end-consumption and its carbon emission reduction is closely related to regional economic and social development, thus identifying the resource and environmental impacts of its carbon emission reduction measures and revealing the regional disparities is the key to realizing the high-quality green and low-carbon transformation of this industry in China. [Methods] This study developed a factory-level comprehensive evaluation model of China’s iron and steel industry that reflects the resource, environmental, and economic linkages based on a bottom-up Asian-Pacific Integrated Model (AIM)/Enduse model. This model predicts crude steel demand under different socioeconomic development paths by 2060, and focuses on identifying the resource and environmental impacts of production structural adjustment, permeation of abatement technologies, carbon policies, and carbon neutral technology measures, revealing the regional disparities and spatial pattern of typical environmental emissions. [Results] (1) With the increase of recyclable scrap stock, the share of crude steel production of short-process will increase from 10.6% (2020) to 70% (2060); (2) With the synergistic effect of various emission reduction measures, the total energy consumption of China’s iron and steel industry will decrease by 70%-76% and fuel consumption will be reduced by 92% in 2060, compared with 2020 (with the share of coal decreasing to 0 and biomass increasing by 69%, and the consumption of coke, which has the property of a reducing agent, will fall by 90%), and carbon dioxide emissions will decrease by 89%-91%; but the increase in methane, organic carbon, and mercury emissions needs to be a cause for concern; (3) Under the synergistic effect of multiple emission reduction measures, there are obvious differences in carbon emission reduction at the provincial level in the iron and steel industry under different crude steel demand paths, and there is a larger number of provinces that show an increasing trend of mercury emissions under the scenario of high crude steel demand; [Conclusion] Therefore, carbon emission reduction in China’s iron and steel industry should be strengthened by systematic planning to prevent the “canceling out” effects among environmental emission factors generated by emission reduction measures, and the high-quality green and low-carbon transformation of China’s iron and steel industry should take into full consideration of regional economic and social disparities as well as resource endowment and carrying capacity.

Abstract Post-stroke depression (PSD) is regarded as the consequence of multiple contributors involving the process of cognition, mood and autonomic system, with the specific mechanism unclear yet. As a common type of stroke-heart syndromes, post-stroke arrhythmia shared some common pathogenesis with PSD. We presumed that post-stroke arrhythmia might be an early distinguishable marker for the presence of PSD and aimed to verity their association in this study. Patients with first-ever ischemic stroke were enrolled. The presence of post-stroke ectopic arrhythmia and the symptoms of arrhythmia were recorded with anti-arrhythmia drugs prescribed when necessary. Patients were followed up 3 months later to identify their presence and severity of PSD using Hamilton Depression Scale (HAMD) and also presence and severity of arrhythmia. Characteristics including the prevalence of various types of arrhythmias were compared between PSD and non-PSD groups. The HAMD scores were compared between patients with and without arrhythmia in PSD group. Logistic regression was used to identify the independent predictor of PSD. Patients with PSD had higher prevalence of post-stroke arrhythmia especially newly-detected arrhythmia, symptomatic arrhythmia and poor-controlled arrhythmia. In PSD group, patients of post-stroke arrhythmia had higher scores of HAMD than those without arrhythmia. Presence of newly-detected, symptomatic and poor-controlled arrhythmias were independent predictor of PSD. post-stroke arrhythmia especially newly-detected arrhythmia and symptomatic arrhythmia could be an early predictor of PSD. Successful control of arrhythmia was associated with reduced prevalence and severity of PSD.

The Coptidis Rhizoma and Bovis Calculus herb pair possesses clearing heat and detoxifying effects. The aim of this study was to reveal the effects and mechanisms of the herb pair in the treatment of NASH by network pharmacology and experimental verification. A network pharmacology-based approach was employed to predict the putative mechanism of the herb pair against NASH. The high-fat diet (HFD) and methionine/choline deficient (MCD) diet induced NASH models were used to evaluate efficacy and mechanism of the herb pair. Network pharmacological analysis showed that the herb pair modulated NOD-like receptor pathway. In the HFD mice, herb pair reduced body weight, blood sugar, serum ALT, AST, TBA, TC, TG and LDL-C contents, also improved the general morphology and pathological manifestations. Hepatic transcriptomics study showed that herb pair attenuated NASH by regulating NOD-like receptor signaling pathway. Western blotting showed that herb pair reduced the protein expression levels of NLRP3, cleaved Caspase-1 and cleaved IL-1β. In the MCD mice, herb pair also reduced serum ALT, ALT and TBA levels, improved liver pathological manifestations, inhibited the protein expression levels of NLRP3, cleaved Caspase-1 and cleaved IL-1β. Our findings proved that the Coptidis Rhizoma and Bovis Calculus herb pair attenuates NASH through suppression of NLRP3 inflammasome activation. This will demonstrate effective pharmacological evidence for the clinical application of herb pair.

Periodontitis is a chronic inflammatory disease associated with dysbiosis in subgingival plaque biofilm, characterised by damage to the periodontal tissues, eventually leading to tooth loss. Hence, the pathophysiology of periodontitis and interaction between subgingival plaque and host tissue under various environmental cues are central to the pathogenesis of periodontitis. Therefore, engineering biofilm models that mimic in vivo pathophysiology is crucial to obtaining a clear insight into the pathology and developing targeted therapeutic methods. In this review, we provide a comprehensive overview of the engineering strategies employed of modelling oral biofilms focusing on surface attachment, fluid microenvironment, gas environment, shear force, microbial-host interaction and offer insights into the ongoing challenges and future perspectives, which will enable the development of novel physiological relevant models for oral biofilms.

Abstract Objective The aim of this study was to determine the psychological status of peritoneal dialysis (PD) patients who were blocked during the 2022 Omic Pandemic in Shanghai. Methods This was an observational and cross-sectional study. We selected 172 PD patients from the peritoneal dialysis center of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, during the quarantine of the Omicron pandemic in Shanghai from April to May 2022. General data and biochemical indices were collected. The Kidney Disease Quality of Life (SF-36) questionnaire was used to evaluate the psychological state of the patients during the quarantine. Results According to the assessment of the SF-36 scale, the physiological and psychological health status of PD patients was better than that before quarantine (P 0.05). According to the results of the abstract independent sample T test, when comparing the various dimensions of the SF-36 scale, for the dimensions of physiological function, pain and energy, the PD patients were better than the HD patients were (P

Photovoltaic power generation and photothermal power generation are two forms of solar power generation. The development cost of photovoltaic is relatively lower than photothermal, but a certain proportion of energy storage and distributed synchronous condensers are needed to ensure the safe and stable operation of the system. As a result the cost of photovoltaic power generation rises. Photothermal comes with heat storage and output friendliness, so currently there is still a great dispute about the technical route of photovoltaic and photothermal. This paper takes Haixi area of Qinghai province as an example. Firstly, based on the characteristics of solar irradiation resources and output in the same time and space, the power guarantee capabilities of photovoltaic+energy storage and photothermal is compared. Then this paper compares photovoltaic+energy storage+condenser with photothermal from the perspective of power grid security and stability support ability. Finally, this paper compares the economics of solar thermal and photovoltaic based on the forecast of their cost declining trend. Photothermal has both thermal storage and conventional generator functions, providing short circuit capacity, reactive power compensation and moment of inertia support for the system. The results show the economy of photothermal is basically equivalent to, or even better than photovoltaic+energy storage+condenser after the cost reduction in the case of technical equivalence.

Postpartum women present a high risk of disordered eating behaviors, but the heterogeneity between groups was not identified. This cross-sectional study aimed to identify eating styles profiles in postpartum women and explore the correlates based on demographic characteristics and psychosocial factors. Questionnaires were administered to 507 Chinese postpartum women. Latent profile analysis (LPA) was conducted to identify eating styles profiles. Multinomial logistic regression was used to investigate the correlates of these profiles among postpartum women. The LPA identified three eating styles profiles: postpartum women with low emotional, external, and restrained eating (Profile 1, 6.9%); postpartum women with medium emotional, external, and restrained eating (Profile 2, 66.1%); and postpartum women with high emotional, external, and restrained eating (Profile 3, 27.0%). Compared to Profile 1, higher postpartum depression (PPD) and body mass index (BMI) were more likely to be associated with Profile 2 and Profile 3, whereas higher postpartum weight retention (PPWR) was more likely to be associated with Profile 1. Compared to Profile 2, higher PPD and BMI were more likely associated with Profile 3. Disordered eating behaviors in postpartum women with three eating styles were associated with BMI, PPD, and PPWR. This study can guide healthcare professionals in developing targeted interventions to improve maternal and child health globally.

IntroductionThe natural outcome of coronary plaque in acute coronary syndrome (ACS) patients with chronic kidney disease (CKD) is unique, which can be analyzed quantitatively by optical flow ratio (OFR) software.MethodsA total of 184 ACS patients with at least one nonculprit subclinical atherosclerosis (NSA) detected by optical coherence tomography (OCT) at baseline and 1-year follow-up were divided into non-CKD group (n = 106, estimated glomerular filtration rate (eGFR)> 90 mL/(min×1.73 m2)) and mild CKD group (n = 78, 60≤eGFRResultsPatients with mild CKD showed more TAVn progression of NSA than non-CKD (p = 0.019) from baseline to the 1-year follow-up, which was mainly due to an increase in calcium TAVn (pConclusionsMild CKD patients had more plaque progression of NSA which showed the increase of calcium component with more protrusion into the lumen morphologically at the 1-year follow-up and a higher corresponding incidence of NSA-related MACEs at the 5-year follow-up.Trial registrationClinical Trial registration ClinicalTrials.gov. NCT02140801. https://classic.clinicaltrials.gov/ct2/show/NCT02140801.

Abstract Objective This study aims to provide an academic summary of the clinical characteristics, outcomes and risk factors associated with prolonged hospital stays among the patients with varying renal function statuses during the Omicron pandemic in Shanghai. Methods Clinical data was collected from COVID-19 patients admitted to Shanghai Jiaotong University School of Medicine Ruijin Hospital Northern District. Based on their baseline eGFR, the patients were divided into three groups: Group A (eGFR > = 90ml/min/1.73m2, n = 384), Group B (15ml/min/1.73m2

In this study, octenyl succinic anhydride-modified starch (OSA starch) with different degrees of substitution (DS) was used as raw materials, which was combined with chitosan (CS) to make a complex. The effects of DS on the change of functional groups and wettability of the complex were studied. Pickering emulsions stabilized by OSA starch/chitosan complexes with different volume fractions of oil phase (20%, 50%, 80%) were prepared, and the effects of DS and volume fractions of oil phase on the stability of the emulsion were investigated. The results showed that the hydrophobicity increased significantly with the DS of OSA starch increasing. When the addition amount of octenyl succinic anhydride (OSA) was 2%, the contact angle of the complex was closest to 90°, which showed the suitable wettability. With the DS or the volume fraction of oil phase increasing, the diameters of emulsion particles increased, the droplet distribution became more even and dense, and the emulsion state got closely to solid. Moreover, the volume fraction of oil phase had more prominent effects on the emulsion. When DS was 0.00895 and the volume fraction of emulsion oil phase was 80%, the emulsion average particle size was 27.4±1.4 μm and had gel network structures. After storaging under −4 ℃ for 30 days, the emulsion had no creaming phenomenon and exhibited good ionic and temperature stability. This study further explored the parameter settings of Pickering emulsion stabilized by OSA starch-polysaccharide complexes, which was expected to promote the development and application of this emulsion.

Abstract Background Chronic kidney disease (CKD) accelerates atherosclerosis, but the mechanisms remain unclear. Tyrosine sulfation has been recognized as a key post-translational modification (PTM) in regulation of various cellular processes, and the sulfated adhesion molecules and chemokine receptors have been shown to participate in the pathogenesis of atherosclerosis via enhancement of monocyte/macrophage function. The levels of inorganic sulfate, the essential substrate for the sulfation reaction, are dramatically increased in patients with CKD, which indicates a change of sulfation status in CKD patients. Thus, in the present study, we detected the sulfation status in CKD patients and probed into the impact of sulfation on CKD-related atherosclerosis by targeting tyrosine sulfation function. Results PBMCs from individuals with CKD showed higher amounts of total sulfotyrosine and tyrosylprotein sulfotransferase (TPST) type 1 and 2 protein levels. The plasma level of O-sulfotyrosine, the metabolic end product of tyrosine sulfation, increased significantly in CKD patients. Statistically, O-sulfotyrosine and the coronary atherosclerosis severity SYNTAX score positively correlated. Mechanically, more sulfate-positive nucleated cells in peripheral blood and more abundant infiltration of sulfated macrophages in deteriorated vascular plaques in CKD ApoE null mice were noted. Knockout of TPST1 and TPST2 decreased atherosclerosis and peritoneal macrophage adherence and migration in CKD condition. The sulfation of the chemokine receptors, CCR2 and CCR5, was increased in PBMCs from CKD patients. Conclusions CKD is associated with increased sulfation status. Increased sulfation contributes to monocyte/macrophage activation and might be involved in CKD-related atherosclerosis. Inhibition of sulfation may suppress CKD-related atherosclerosis and is worthy of further study.

Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia.

Abstract Background Insects rely on chemosensory perception, mainly olfaction, for the location of mates, food sources, and oviposition sites. Plant-released volatile compounds guide herbivorous insects to search for and locate their host plants, further helping them to identify suitable positions for oviposition. The fall armyworm Spodoptera frugiperda (S. frugiperda) was found to invade China in 2019 and has since seriously threatened multiple crops, particularly maize and rice. However, the chemical and molecular mechanisms underlying oviposition preference in this pest are not fully understood. Here, the oviposition preference of S. frugiperda on maize and rice plants was investigated. Results GC-EAD and GC–MS/MS techniques were used to identify the antennally active volatiles from maize and rice plants. The attraction and oviposition stimulation of identified components to female adults were tested in both laboratory and field settings. The odorant receptors (ORs) on female antennae were expressed in Xenopus oocytes, and their functions evaluated by RNAi. Ten and eleven compounds of maize and rice plants, respectively, were identified to possess electrophysiological activity from headspace volatiles. Among these compounds, (Z)-3-hexenyl-acetate specifically presented in maize volatiles was found to play a critical role in attracting females and stimulating oviposition compared to rice volatiles. Among the cloned ORs on the antennae of both sexes, SfruOR23 with highly female-biased expression mediated the responses of females to (Z)-3-hexenyl-acetate. Knockdown of SfruOR23 using RNAi markedly reduced the electrophysiological response of female antennae and oviposition preference to the compound. Conclusions (Z)-3-Hexenyl-acetate is a key volatile mediating the host and oviposition preference of S. frugiperda on maize. The olfactory receptor of (Z)-3-hexenyl-acetate was identified to be SfruOR23, which is mainly expressed in the antennae of S. frugiperda.

Abstract Background Immune checkpoint inhibitors (ICI)-based combination strategies have improved the survival outcomes in advanced non-small cell lung cancers; however, data regarding their efficacy remains limited for uncommon histological types, including large-cell carcinoma (LCC) and large-cell neuroendocrine carcinoma (LCNEC). Methods We retrospectively analyzed a total of 60 patients with advanced LCC and LCNEC – 37 treatment-naïve and 23 pre-treated – who received pembrolizumab with or without chemotherapy. Treatment and survival outcomes were analyzed. Results Of the 37 treatment-naïve patients who received first-line pembrolizumab combined with chemotherapy, the 27 patients with LCC had an overall response rate (ORR) of 44.4% (12/27) and a disease control rate (DCR) of 88.9% (24/27); whereas 10 patients with LCNEC had an ORR of 70% (7/10) and DCR of 90% (9/10). The median progression-free survival (mPFS) was 7.0 months (95% confidence intervals [CI]: 2.2–11.8) and median overall survival (mOS) was 24.0 months (95%CI: 0.0–50.1) for first-line pembrolizumab plus chemotherapy of LCC (n = 27), whereas mPFS was 5.5 months (95%CI: 2.3–8.7) and mOS was 13.0 months (95%CI: 11.0–15.0) for first-line pembrolizumab plus chemotherapy of LCNEC (n = 10). Of the 23 pre-treated patients who received subsequent-line pembrolizumab with or without chemotherapy, mPFS was 2.0 months (95% CI: 0.6–3.4) and mOS was 4.5 months (95% CI: 0.0–9.0) for LCC and mPFS was 3.8 months (95% CI: 0.0–7.6) and mOS was not reached for LCNEC. Conclusion Our study provides real-world clinical evidence of the anti-tumor activity of pembrolizumab plus chemotherapy in advanced LCC and LCNEC, indicating that this regimen could serve as a treatment option, particularly as first-line therapy, for improving the survival outcomes of patients with these rare histological subtypes of lung cancer. Trial registration NCT05023837(ESPORTA, 27/08/2021).

Abstract Although patients are undergoing similar lipid-lowering therapy (LLT) with statins, the outcomes of coronary plaque in diabetic mellitus (DM) and non-DM patients are different. Clinical data of 239 patients in this observational study with acute coronary syndrome was from our previous randomized trial were analyzed at 3 years, and 114 of them underwent OCT detection at baseline and the 1-year follow-up were re-anlayzed by a novel artificial intelligence imaging software for nonculprit subclinical atherosclerosis (nCSA). Normalized total atheroma volume changes (ΔTAVn) of nCSA were the primary endpoint. Plaque progression (PP) was defined as any increase in ΔTAVn. DM patients showed more PP in nCSA (ΔTAVn; 7.41 (− 2.82, 11.85) mm3 vs. − 1.12 (− 10.67, 9.15) mm3, p = 0.009) with similar reduction of low-density lipoprotein cholesterol (LDL-C) from baseline to 1-year. The main reason is that the lipid component in nCSA increases in DM patients and non-significantly decreases in non-DM patients, which leads to a significantly higher lipid TAVn (24.26 (15.05, 40.12) mm3 vs. 16.03 (6.98, 26.54) mm3, p = 0.004) in the DM group than in the non-DM group at the 1-year follow-up. DM was an independent predictor of PP in multivariate logistic regression analysis (OR = 2.731, 95% CI 1.160–6.428, p = 0.021). Major adverse cardiac events (MACEs) related to nCSA at 3 years were higher in the DM group than in the non-DM group (9.5% vs. 1.7%, p = 0.027). Despite a comparable reduction in LDL-C levels after LLT, more PP with an increase in the lipid component of nCSA and a higher incidence of MACEs at the 3-year follow-up was observed in DM patients. Trial registration: ClinicalTrials.gov. identifier: NCT02140801.

ABSTRACTProduction of site-specific cysteine-engineered antibody-drug conjugates (ADCs) in mammalian cells may produce developability challenges, fragments, and heterogenous molecules, leading to potential product critical quality attributes in later development stages. Liquid phase chromatography with mass spectrometry (LC-MS) is widely used to evaluate antibody impurities and drug-to-antibody ratio, but faces challenges in analysis of fragment product variants of cysteine-engineered ADCs and oligonucleotide-to-antibody ratio (OAR) species of antibody-oligonucleotide conjugates (AOCs). Here, for the first time, we report novel capillary zone electrophoresis (CZE)-MS approaches to address the challenges above. CZE analysis of six ADCs made with different parent monoclonal antibodies (mAbs) and small molecule drug-linker payloads revealed that various fragment impurities, such as half mAbs with one/two drugs, light chains with one/two drugs, light chains with C-terminal cysteine truncation, heavy chain clippings, were well resolved from the main species. However, most of these fragments were coeluted or had signal suppression during LC-MS analysis. Furthermore, the method was optimized on both ionization and separation aspects to enable the characterization of two AOCs. The method successfully achieved baseline separation and accurate quantification of their OAR species, which were also highly challenging using conventional LC-MS methods. Finally, we compared the migration time and CZE separation profiles among ADCs and their parent mAbs, and found that properties of mAbs and linker payloads significantly influenced the separation of product variants by altering their size or charge. Our study showcases the good performance and broad applicability of CZE-MS techniques for monitoring the heterogeneity of cysteine-engineered ADCs and AOCs.

AbstractBackground Ectopic calcification (EC) involves multiple organ systems in chronic kidney disease (CKD). Previous CKD-animal models primarily focused on a certain histological abnormality but did not show the correlation with calcified development among various tissues. This study compared calcified deposition in various tissues during CKD progression in mice.Methods Male 8-week-old C57BL/6J mice were randomly allocated to the seven groups: a basic, adenine, high-phosphorus, or adenine and high-phosphorus diet for 12–16 weeks (Ctl16, A12, P16, or AP16, respectively); an adenine diet for 4–6 weeks; and a high-phosphorus or adenine and high-phosphorus diet for 10–12 weeks (A6 + P10, A4 + P12, or A4 + AP12, respectively).Results Compared to the Ctl16 mice, the P16 mice only displayed a slight abnormality in serum calcium and phosphorus; the A12 mice had the most serious kidney impairment; the A4 + P12 and A6 + P10 mice had similar conditions of CKD, mineral abnormalities, and mild calcification in the kidney and aortic valves; the A4 + AP12 and AP16 groups had severe kidney impairment, mineral abnormalities and calcification in the kidneys, aortic valves and aortas. Furthermore, calcium-phosphate particles were deposited not only in the tubulointerstitial compartment but in the glomerular and tubular basement membrane. The elemental composition of EC in various tissues matched the calcification of human cardiovascular tissue as determined by energy dispersive spectroscopy.Conclusions The severity of CKD was unparalleled with the progression of mineral metabolism disorder and EC. Calcification was closely related in different tissues and observed in the glomerular and tubular basement membranes.

BackgroundSleep is an important biological process and has been linked to many diseases; however, very little is known about which and how genes control and regulate sleep. Although technology has seen significant development, this issue has still not been adequately resolved. Therefore, we conducted a bibliometric analysis to assess the progress in research on sleep quality and associated genes over the past 2 decades. Through our statistical data and discussions, we aimed to provide researchers with better research directions and ideas, thus promoting the advancement of this field.MethodsOn December 29, 2022, we utilized bibliometric techniques, such as co-cited and cluster analysis and keyword co-occurrence, using tools such as CiteSpace, VOSviewer, and the Online Analysis Platform of Literature Metrology (http://bibliometric.com/), to conduct a thorough examination of the relevant publications extracted from the Web of Science Core Collection (WoSCC). Our analysis aimed to identify the emerging trends and hot spots in this field while also predicting their potential development in future.ResultsCluster analysis of the co-cited literature revealed the most popular terms relating to sleep quality and associated genes in the manner of cluster labels; these included genome-wide association studies (GWAS), circadian rhythms, obstructive sleep apnea (OSA), DNA methylation, and depression. Keyword burst detection suggested that obstructive sleep apnea, circadian clock, circadian genes, and polygenic risk score were newly emergent research hot spots.ConclusionBased on this bibliometric analysis of the publications in the last 20 years, a comprehensive analysis of the literature clarified the contributions, changes in research hot spots, and evolution of research techniques regarding sleep quality and associated genes. This research can provide medical staff and researchers with revelations into future directions of the study on the pathological mechanisms of sleep-related diseases.

Background We aimed to evaluate the relationships between the magnitude of systolic blood pressure (SBP) reduction and achieved SBP in the acute phase of ischemic stroke onset and subsequent clinical outcomes. Methods and Results This study was a secondary analysis of CATIS (China Antihypertensive Trial in Acute Ischemic Stroke), a multicenter randomized controlled trial of 4071 patients with acute ischemic stroke. SBP reduction was defined as the proportional SBP changes from baseline to 24 hours after randomization, and achieved SBP was the mean of SBP measurements at day 7. The study outcomes included functional outcome of death or major disability (modified Rankin Scale score ≥3), death, and cardiovascular events at 3 months after recruitment. Compared with the reference group of increase or no change in SBP within the first 24 hours, the odds ratios (95% CIs) of functional outcome of death or major disability were 0.62 (0.47–0.83) and 0.61 (0.42–0.87) for the reduction of 11% to 20% and >20%, respectively. Compared with participants in highest achieved SBP group (≥160 mm Hg) at day 7, odds ratios or hazard ratios of lower achieved SBP (

The coupled seepage–stress action has a significant deterioration effect on the structural face of the hydraulic tunnel enclosure, which intensifies the shear rupture tendency of the deteriorated structural face of the rock mass. The plastic deformation of a typical I–II composite fissure was taken as the research object, the characteristics of the tip plastic zone of the composite fissure seepage rock were explored, and the influence law of osmotic pressure and fissure rock parameters (fissure dip angle, Poisson’s ratio, and fissure length) on the radius of the tip plastic zone was analyzed. Based on the Drucker–Prager yield criterion and the stress intensity factor of the composite fracture, the theoretical analytical formula of the fracture plastic zone radius under the action of high and low osmotic pressure was established, and the fracture rock plastic zone radius was significantly correlated with the fracture parameters. The radius of the plastic zone of fracture under low osmotic pressure evolves in a trend of decreasing–increasing–decreasing with the increase in fracture dip angle, and the peak radius of the plastic zone appears at 45°. Poisson’s ratio and fracture length have less influence on the radius of the plastic zone. The radius of the plastic zone of fracture under high osmotic pressure grows in an incremental nonlinear curve, and the peak radius of the plastic zone appears at 90°, being positively correlated with the length of fracture. This study can provide theoretical reference for the analysis of the stability of the surrounding rock in hydraulic tunnels.

Conifers have evolved sophisticated terpenoid defenses for protection against herbivores and pathogens. Pinus massoniana Lamb. is the most widely distributed pioneer afforestation and resin tree species in China, but is seriously harmed by pine wilt disease. Monochamus alternatus is the main vector of pine wilt disease in China. Monoterpenes, sesquiterpenes and diterpenes, the main secondary defensive compounds of P. massoniana, are catalyzed by different terpene synthases (TPSs), which participate in the important defense pathways against external biotic and abiotic stresses. Here, we aimed to identify the terpene synthases (TPSs) in P. massoniana, responding to the feeding of M. alternatus, and to characterize the functions and products of the mono-TPSs. We identified six differentially expressed TPS genes in the P. massoniana fed upon by M. alternatus, including four mono-TPS and two sesqui-TPS genes. The functions of the four mono-TPSs were verified by analysis of the main product and by-products of these mono-TPSs. (+)-α-Pinene, (−)-α-pinene, and limonene were the major products of TPS (+)-α-pinene, TPS (−)-α-pinene, and TPS limonene, respectively, but TPS (−)-β-pinene only catalyzed a trace amount of (−)-β-pinene in the products. Our findings shed light on the potential relationships between the structure of terpene synthases and their corresponding products.

BackgroundThe clinical progression of individuals afflicted with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection exhibits significant heterogeneity, particularly affecting the elderly population to a greater extent. Consequently, the association between nutrition and microbiota has garnered considerable interest. Hence, the objective of this study was to gather clinical data pertaining to the influence of diverse nutritional support interventions on the prognosis of geriatric patients with COVID-19, while additionally examining the fecal microbiota of these individuals to assess the repercussions of microecological alterations on their prognostic outcomes.ResultsA total of 71 elderly patients diagnosed with severe COVID-19 were included in this study. These patients were subsequently divided into two groups, namely the enteral nutrition (EN) group and the parenteral nutrition (PN) group, based on the type of nutritional support therapy they received after admission. The occurrence of complications was observed in 10.4% of patients in the EN group, whereas it was significantly higher at 69.6% in the PN group (P

In life science, protein is an essential building block for life forms and a crucial catalyst for metabolic reactions in organisms. The structures of protein depend on an infinity of amino acid residues' complex combinations determined by gene expression. Predicting protein folding structures has been a tedious problem in the past seven decades but, due to robust development of artificial intelligence, astonishing progress has been made. Alphafold2, whose key component is Evoformer, is a typical and successful example of such progress. This article attempts to not only isolate and dissect every detail of Evoformer, but also raise some ideas for potential improvement.

Abstract The association between gut microbiome and chronic metabolic disease including polycystic ovary syndrome (PCOS), is well documented, however, the relationship between the gut microbiota and serum metabolites remains unknown. In this study, untargeted metabolomics together with a 16S rRNA gene sequencing tool was used to detect small molecule serum metabolites and the gut microbiome. We identified 15 differential metabolites between PCOS patients and the healthy control. Lysophosphatidylcholine (LPC) (18:2, 20:3, 18:1, P-16:0, 17:0, 15:0, 18:3, 20:4), phosphatidylcholine(PC), ganglioside GA2 (d18:1/16:0) and 1-linoleoylglycerophosphocholine were increased in the PCOS group, and the concentrations of phosphoniodidous acid, bilirubin, nicotinate beta-d-ribonucleotide and citric acid were decreased in the PCOS group, suggesting a lipid metabolism and energy metabolism disorder in the PCOS patients. The diversity of gut microbiota in PCOS group was lower than that in healthy controls. Escherichia/Shigella, Alistipes and an unnamed strain 0319_6G20 belonging to Proteobacteria were important distinguishing genera (LDA > 3.5) in PCOS. Prevotella_9 was positively correlated with phosphoniodidous acid, nicotinate beta-d-ribonucleotide and citric acid concentrations, and negatively correlated with the concentration of LPC (20:3) and 1-linoleoylglycerophosphocholine; Roseburia was negatively correlated with LPC concentration (20:4), while the characteristic genus 0319_6G20 of PCOS was positively correlated with LPC concentration (20:3) (COR > 0.45). SF-36 in the PCOS group was significantly lower than that in the healthy control (HC) group, which was associated with the presence of Escherichia-Shigella and Alistipes. Our finding demonstrated the correlation between the gut microbiota and serum metabolites in PCOS, and therefore characteristic gut microbiota and metabolites may play an important role in the insulin resistance and the mood changes of PCOS patients.

Abstract Micrognathia is a severe craniofacial deformity affecting appearance and survival. Previous studies revealed that multiple factors involved in the osteogenesis of mandibular bone have contributed to micrognathia, but concerned little on factors other than osteogenesis. In the current study, we found that ectopic activation of Fgf8 by Osr2-cre in the presumptive mesenchyme for masseter tendon in mice led to micrognathia, masseter regression, and the disrupted patterning and differentiation of masseter tendon. Since Myf5-cre;Rosa26R-Fgf8 mice exhibited the normal masseter and mandibular bone, the possibility that the micrognathia and masseter regression resulted directly from the over-expressed Fgf8 was excluded. Further investigation disclosed that a series of chondrogenic markers were ectopically activated in the developing Osr2-cre;Rosa26R-Fgf8 masseter tendon, while the mechanical sensing in the masseter and mandibular bone was obviously reduced. Thus, it suggested that the micrognathia in Osr2-cre;Rosa26R-Fgf8 mice resulted secondarily from the reduced mechanical force transmitted to mandibular bone. Consistently, when tenogenic or myogenic components were deleted from the developing mandibles, both the micrognathia and masseter degeneration took place with the decreased mechanical sensing in mandibular bone, which verified that the loss of mechanical force transmitted by masseter tendon could result in micrognathia. Furthermore, it appeared that the micrognathia resulting from the disrupted tenogenesis was attributed to the impaired osteogenic specification, instead of the differentiation in the periosteal progenitors. Our findings disclose a novel mechanism for mandibular morphogenesis, and shed light on the prevention and treatment for micrognathia.

Abstract Background Nutritional risk is prevalent in various diseases, but its association with contrast-induced acute kidney injury (CI-AKI) remains unclear. This study aimed to explore this association in patients undergoing coronary angiography (CAG). Methods In this retrospective cross-sectional study, 4386 patients undergoing CAG were enrolled. Nutritional risks were estimated by nutritional risk screening 2002 (NRS-2002), controlling nutritional status (CONUT), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), respectively. CI-AKI was determined by the elevation of serum creatinine (Scr). Multivariable logistic regression analyses and receiver operator characteristic (ROC) analyses were conducted. Subgroup analyses were performed according to age (

Abstract Background For colorectal cancer, preoperative (neoadjuvant) chemotherapy is more effective than postoperative chemotherapy because it not only eradicates micrometastases more effectively but also reduces the risk of incomplete intraoperative resection and tumor cell shedding. For the treatment of acute left-sided malignant colorectal obstruction, colorectal stents as well as stoma are being used to relieve the obstructive colorectal cancer, and as a bridge to surgery, allowing easy mobilization and resection of the colon. Neoadjuvant chemotherapy combined with self-expandable metal stents (SEMS) or neoadjuvant chemotherapy combined with decompressing stoma (DS) can be used as a bridge to elective surgery (BTS) as an alternative to emergency surgery in patients with acute left-sided malignant colorectal obstruction, but its benefit is uncertain. The purpose of this study was to evaluate the safety and feasibility of neoadjuvant chemotherapy as a bridge to surgery in the treatment of acute left-sided malignant colorectal obstruction. Methods Data from patients who were admitted with acute left-sided malignant colorectal obstruction between January 2012 and December 2020 were retrospectively reviewed, and patients with gastrointestinal perforation or peritonitis were excluded. We performed one-to-two propensity score matching to compare the stoma requirement, postoperative complications, and other short-term oncological outcomes between the neoadjuvant chemotherapy group and surgery group. Results There were no differences in intraoperative blood loss, operative time, one-year postoperative mortality, and postoperative tumor markers between the two groups. The 1-year recurrence-free survival (RFS) rates of neoadjuvant chemotherapy group and surgery group were 96.8 and 91.3% (p = 0.562). The neoadjuvant chemotherapy group was able to reduce stoma rate 1 year after surgery (p = 0.047). Besides, the neoadjuvant group significantly reduced postoperative bowel function time (p

Background and aimsNon-alcoholic fatty liver disease(NAFLD) is common worldwide and has previously been reported to be associated with sleep traits. However, it is not clear whether NAFLD changes sleep traits or whether the changes in sleep traits lead to the onset of NAFLD. The purpose of this study was to investigate the causal relationship between NAFLD and changes in sleep traits using Mendelian randomization.MethodsWe proposed a bidirectional Mendelian randomization (MR) analysis and performed validation analyses to dissect the association between NAFLD and sleep traits. Genetic instruments were used as proxies for NAFLD and sleep. Data of genome-wide association study(GWAS) were obtained from the center for neurogenomics and cognitive research database, Open GWAS database and GWAS catalog. Three MR methods were performed, including inverse variance weighted method(IVW), MR-Egger, weighted median.ResultsIn total,7 traits associated with sleep and 4 traits associated with NAFLD are used in this study. A total of six results showed significant differences. Insomnia was associated with NAFLD (OR(95% CI)= 2.25(1.18,4.27), P = 0.01), Alanine transaminase levels (OR(95% CI)= 2.79(1.70, 4.56), P =4.71×10-5) and percent liver fat(OR(95% CI)= 1.31(1.03,1.69), P = 0.03). Snoring was associated with percent liver fat (1.15(1.05,1.26), P =2×10-3), alanine transaminase levels (OR(95% CI)= 1.27(1.08,1.50), P =0.04).And dozing was associated with percent liver fat(1.14(1.02,1.26), P =0.02).For the remaining 50 outcomes, no significant or definitive association was yielded in MR analysis.ConclusionGenetic evidence suggests putative causal relationships between NAFLD and a set of sleep traits, indicating that sleep traits deserves high priority in clinical practice. Not only the confirmed sleep apnea syndrome, but also the sleep duration and sleep state (such as insomnia) deserve clinical attention. Our study proves that the causal relationship between sleep characteristics and NAFLD is the cause of the change of sleep characteristics, while the onset of non-NAFLD is the cause of the change of sleep characteristics, and the causal relationship is one-way.

BackgroundElevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). However, low adherence to medication and lifestyle management has limited the benefits of lowering lipid levels. Cognitive behavioral therapy (CBT) has been proposed as a promising solution. ObjectiveThis trial aimed to evaluate the efficacy of mobile-based CBT interventions in lowering LDL-C levels in patients with ASCVD. MethodsThis multicenter, prospective, randomized controlled trial enrolled 300 patients with ASCVD, who were randomly assigned to the mobile-based CBT intervention group and the control group in a ratio of 1:1. The intervention group received CBT for ASCVD lifestyle interventions delivered by WeChat MiniApp: “CBT ASCVD.” The control group only received routine health education during each follow-up. The linear regression and logistic regression analyses were used to determine the effects of a mobile-based CBT intervention on LDL-C, triglyceride, C-reactive protein, the score of General Self-Efficacy Scale (GSE), quality of life index (QL-index), and LDL-C up-to-standard rate (

IntroductionThe essence of enterotypes is to stratify the entire human gut microbiota, and dysregulation of gut microbiota is closely related to the development of colorectal adenoma. Enterotypes may therefore be a useful target for the prevention of colorectal adenoma. However, the relationship between gut microbiota and colorectal adenoma has not been fully elucidated. In this study, we aimed to analyze the differences in gut microbiome composition between adenoma and control populations.MethodsWe recruited 31 patients with colorectal adenoma and 71 non-adenoma controls. Patient demographics, risk factors, fecal samples from each subject were collected and metagenomic sequencing was performed. LEfSe analysis was used to reveal differences in intestinal microbiome composition. Multiple logistic regression analysis was used to determine the association between enterotypes and colorectal adenoma.ResultsThe results showed that Prevotella enterotype (enterotype 4) is only present in adenoma group. Logistic regression analysis showed that Prevotella enterotype was an independent risk factor for colorectal adenoma.DiscussionThe Prevotella enterotype may increase the occurrence of colorectal adenoma through inflammatory association and interference with glucose and lipid metabolism in human body. In conclusion, the differences we observed between different enterotypes add a new potential factor to the development of colorectal adenoma.

The longicorn beetle Monochamus saltuarius (Coleoptera; Cerambycidae) is an insect vector that transmits the pine wood nematode Bursaphelenchus xylophilus, a serious issue in pine forests in China, Japan, and South Korea. Dastarcus helophoroides and Scleroderma guani are effective in controlling M. saltuarius. However, the application of these parasites for the direct control of vector insects requires detailed analyses of the suitability of the selected natural enemies in potential pest areas, particularly under climate change. Based on species distribution records as well as the current and projected climate change trends up to 2050, we utilized an optimized Maxent algorithm to predict the potential distribution patterns of M. saltuarius and its natural enemies in China. Furthermore, we estimated Schoener’s D to quantify the overlap in adaptability between M. saltuarius and its natural enemies. The potentially suitable areas predicted under the current climate conditions were concentrated mainly in northeast and north China. Additional suitable areas were detected in central, eastern, northwestern, and southwestern China. Under future climate conditions, the suitable range of M. saltuarius gradually shifted southward, with a tendency to expand into high-altitude and colder regions, such as Sichuan, Qinghai, and Tibet. The potential distribution of the natural enemies D. helophoroides and S. guani continued to expand under climate change. A comparison of the appropriate habitats of M. saltuarius and natural enemy insects indicated that D. helophoroides is more suitable for initial biological control in north, northeast, and central China as well as certain northwest and coastal regions. S. guani could be prioritized for nationwide release, while joint control using both species may be effective in Liaoning, Hebei, and Tianjin provinces. These analyses demonstrate that future climate change is likely to exert adverse effects on the potential distribution of M. saltuarius but is favorable for the potential distributions of natural enemies. This study offers important insights into the effective control of M. saltuarius and provides an experimental basis for the utilization of natural enemies according to the characteristics of different regions.

Pork skin and duck skin are highly favored by consumers in China, and high-temperature processing methods are widely employed in cooking and food preparation. However, the influence of high-temperature treatment on the microbial communities within pork skin and duck skin remains unclear. In this study, a high-temperature treatment method simulating the cooking process was utilized to treat samples of pork skin and duck skin at temperatures ranging from 60 °C to 120 °C. The findings revealed that high-temperature treatment significantly altered the microbial communities in both pork skin and duck skin. Heat exposure resulted in a decrease in microbial diversity and induced changes in the relative abundance of specific microbial groups. In pork skin, high-temperature treatment led to a reduction in bacterial diversity and a decline in the relative abundance of specific bacterial taxa. Similarly, the relative abundance of microbial communities in duck skin also decreased. Furthermore, potential pathogenic bacteria, including Gram-positive and Gram-negative bacteria, as well as aerobic, anaerobic, and facultative anaerobic bacteria, exhibited different responses to high-temperature treatment in pork skin and duck skin. These findings highlighted the substantial impact of high-temperature processing on the composition and structure of microbial communities in pork skin and duck skin, potentially influencing food safety and quality. This study contributed to an enhanced understanding of the microbial mechanisms underlying the alterations in microbial communities during high-temperature processing of pork skin and duck skin, with significant implications for ensuring food safety and developing effective cooking techniques.

Four crisping diets were designed to conduct a feeding experiment to investigate the use of broad bean in the formulated feed of Nile tilapia and optimize its use. The growth performance, muscle characteristics, antioxidant capacity, and intestinal health of Nile tilapia with an initial body weight of 617.32 ± 1.64 g were evaluated after being fed with different diets for 90 days. The results showed no adverse effect on the growth performance of Nile tilapia fed with broad bean diets. Contrastingly, some improvements were found in WGR and SGR, but a lower FCR was obtained. The supplementation of broad beans weakened the antioxidant capacity of fish but did not influence liver health and the immune system. Increasing the amount of broad bean addition can increase muscle quality values, and an embrittling functional package being added to the diet can also improve muscle hardness, adhesiveness, and chewiness of Nile tilapia muscle. In addition, the crisping functional package can be applied to tilapia crisping formulated feed, which helps to improve the integrity of the intestinal tissue structure and optimize the intestinal microbiota of Nile tilapia. The final achievement of this study is to provide a theoretical reference for optimizing the breeding technology of crispy Nile tilapia and developing a specialized crisping diet for the species.

Corrosion poses a significant risk to the safety of energy pipelines, while landslide disasters emerge as the primary threat responsible for triggering pipeline failures across mountainous areas. To date, there is limited research focused on the safety of energy pipelines considering the synergistic effect of corrosion and landslides. The present study proposes a finite element (FE)-based model to assess the condition of corroded pipelines under landslides. The effects of corrosion dimensions (length and depth) and location are determined. A novel equation is finally developed to predict the maximum stress and determine the most disadvantageous position for corroded pipelines under various landslide displacements. The results demonstrate that (1) as the landslide progresses, the pipeline’s stress significantly increases; (2) corrosion depth has a more significant impact on the pipeline condition than the corrosion length, and it is positively correlated with the pipe’s stress; (3) the maximum stress exhibits a nonlinear relationship with the landslide-facing position and the corrosion circumferential location; and (4) when the axial position of the corrosion is more than 6.5 m away from the center of the landslide, the location of maximum stress shifts from the corrosion region to the central section of the pipeline within the landslide. This work contributes to helping pipeline owners to understand the applicability of energy pipelines subjected to the combined effects of corrosion and landslides and provides support for future risk assessment efforts in pipeline integrity management.

Introduction: It is still controversial whether automated peritoneal dialysis (APD) or hemodialysis (HD) is a more favorable choice for the rapid initiation of peritoneal dialysis (PD). Methods: A pilot randomized prospective controlled trial was carried out in Shanghai Ruijin Hospital. Sixty-seven patients who chose long-term PD treatment and needed unplanned dialysis were enrolled and randomized into HD-CAPD group (33 cases) or APD-CAPD group (34 cases) based on the dialysis modality during the transition period (within 14 days from the day PD catheter was implanted). Continuous ambulatory PD started after the transition period. The primary outcome was the decline rates of residual glomerular filtration rate (GFR). Secondary outcomes included the rates of mechanical complications, the rates of infectious complications, and complications of end-stage renal disease. Results: We found residual GFR decline was faster in HD-CAPD group than in APD-CAPD group (0.06 mL/min/w vs. 0.03 mL/min/w, p < 0.01). The incidences of mechanical complications were similar in APD-CAPD group comparing with HD-CAPD group, including hernia (2.9% vs. 3.0%, p = 1.00), catheter malposition (0.02 episodes/patient-months vs. 0.02 episodes/patient-months, p = 0.70), leakage (5.9% vs. 6.1%, p = 1.00), and omental wrap (0 episode vs. 3 episodes, p = 0.368). Though the 1-year overall infection rates were similar (0.03 episodes/patient-months vs. 0.05 episodes/patient-months, p = 0.10), APD-CAPD group had lower rate of bacteremia compared to HD-CAPD group (0 episodes/patient-months vs. 0.02 episodes/patient-months, p < 0.01). Conclusions: Both APD and HD could be used for patients who need to start dialysis in an unplanned manner. APD may have the advantage in protecting residual renal functions among these patients.

Background: Kaposi's sarcoma-associated herpes virus (KSHV) initiate and accelerate the development of Kaposi's sarcoma (KS), and KSHV possesses many cancer-associated genes, including KSHV-derived microRNA miR-K12–1, which has been identified to be closely associated with KS progression. However, the detailed mechanisms by which miR-K12–1 facilitates HIV-related gastrointestinal KS development are still not fully delineated. Objectives: This study strived to evaluate the effect of miR-K12–1 on the progression of HIV-related gastrointestinal KS. Materials and methods: The expression levels of miR‐K12–1 in HIV-related gastrointestinal KS tissues were determined by RT‐qPCR. Proliferation and apoptosis were assessed by colony formation, CCK-8 and flow cytometry, respectively. The expression of all proteins was detected by Western blot. The in vivo effect of miR‐K12–1 on the formation of a tumor was explored by using the mouse xenograft model. Results: In this study, we uncovered that KSHV-miR-K12–1 was upregulated in HIV-related gastrointestinal KS tissues and associated with poor outcome in HIV-related gastrointestinal KS patients. Compared with the control group, after miR-K12–1 inhibitor transfection, BCBL-1 cell viability was decreased, and the cell apoptosis was significantly increased, whereas transfection of miR-K12–1 mimics promoted cell proliferation and mitosis. In addition, our rescuing experiments verified that miR-K12–1 promoted cell proliferation via activating the PI3K/Akt pathway, and inhibition of the PI3K/Akt pathway by LY294002 abrogated the tumor-promoting effects of miR-K12–1 in HIV-related gastrointestinal KS. Conclusions: In summary, we concluded that KSHV-derived miR-K12–1 activate the PI3K/Akt pathway to initiate and accelerate the development of KS, which convinces us that miR-K12–1 can be used as potential biomarkers for KS diagnosis, treatment and prognosis.

IntroductionThe treatment response to neoadjuvant immunochemotherapy varies among patients with potentially resectable non-small cell lung cancers (NSCLC) and may have severe immune-related adverse effects. We are currently unable to accurately predict therapeutic response. We aimed to develop a radiomics-based nomogram to predict a major pathological response (MPR) of potentially resectable NSCLC to neoadjuvant immunochemotherapy using pretreatment computed tomography (CT) images and clinical characteristics.MethodsA total of 89 eligible participants were included and randomly divided into training (N=64) and validation (N=25) sets. Radiomic features were extracted from tumor volumes of interest in pretreatment CT images. Following data dimension reduction, feature selection, and radiomic signature building, a radiomics-clinical combined nomogram was developed using logistic regression analysis.ResultsThe radiomics-clinical combined model achieved excellent discriminative performance, with AUCs of 0.84 (95% CI, 0.74-0.93) and 0.81(95% CI, 0.63-0.98) and accuracies of 80% and 80% in the training and validation sets, respectively. Decision curves analysis (DCA) indicated that the radiomics-clinical combined nomogram was clinically valuable.DiscussionThe constructed nomogram was able to predict MPR to neoadjuvant immunochemotherapy with a high degree of accuracy and robustness, suggesting that it is a convenient tool for assisting with the individualized management of patients with potentially resectable NSCLC.

Gastrectomy can improve the clinical survival rate of gastric cancer patients, while the metabolic disorders caused by gastrectomy, seriously affect the postoperative recovery. In this study, probiotics (including Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis and Bacillus cereus) were used before gastrectomy to explore the effect of probiotics on gastrectomy patients. Our outcomes revealed probiotics could alleviate postoperative inflammation (Leukocyte; P

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has swept the world and poses a serious threat to human health. In the post-pandemic-era, we must remain vigilant against the co-infection of SARS-CoV-2 and other respiratory viruses. More accurate and convenient detection methods are required for the diagnosis of SARS-CoV-2 due to its prolonged existence. In this study, the application value of a novel lyophilized-pellet-based 2019-nCoV nucleic acid diagnostic kit (PCoV-Kit) was evaluated by comparing it with a conventional liquid diagnostic kit (LCoV-Kit). We assessed the sensitivity, precision, accuracy, specificity, and amplification efficiency of PCoV-Kit and LCoV-Kit using diluted SARS-CoV-2 RNA reference materials. The results showed that both kits had high sensitivity, precision, accuracy, and specificity. A total of 2,033 oropharyngeal swab specimens collected during mass screening in Fuzhou in December 2022 were applied for the consistency analysis of the two reagents. In the detection of clinical oropharyngeal swab specimens, although the positive rate of PCoV-Kit (19.28%) was slightly lower than that of LCoV-Kit (20.86%), statistical analysis demonstrated a high degree of consistency between the test results obtained using both kit (χ2 = 1.57, P>0.05; Kappa coefficient = 0.90, 95%CI: 0.88-0.93). In conclusion, the use of lyophilized PCoV-Kit provides a non-inferior assay for the diagnosis of COVID-19.

BackgroundPrevious observational studies have shown an association between smoking and coronary artery disease (CAD) in patients with diabetes. Whether this association reflects causality remains unestablished. This study aimed to explore the causal effect of smoking on CAD in patients with diabetes.MethodsGenetic signatures for smoking were extracted from a large genome-wide association study (GWAS), consisted of up to 1.2 million participants. Four smoking phenotypes were included: smoking initiation, cigarettes per day, age at initiation of regular smoking, and smoking cessation. Genetic associations with CAD in patients with diabetes were extracted from another GWAS, which included 15,666 participants (3,968 CAD cases and 11,696 controls). The analyses were performed using the univariable and multivariable Mendelian randomization (MR) method.ResultsMR analysis revealed that smoking initiation was positively related to CAD risk in patients with diabetes (OR = 1.322, 95% CI = 1.114 – 1.568, P = 0.001), but this association was attenuated when adjusted for cardiovascular risk factors (OR = 1.212, 95% CI = 1.008 – 1.457, P = 0.041). Age at initiation of regular smoking was negatively related to CAD in patients with diabetes (OR = 0.214, 95% CI = 0.070 – 0.656, P = 0.007), but this association became insignificant when adjusted for cardiovascular risk factors.ConclusionsThis study supported the effect of smoking initiation on the risk of CAD in patients with diabetes.

Objective The antibacterial properties and bonding strength of 3M orthodontic adhesive resin modified by chlorhexidine acetate (CHA) composite mesoporous silica were investigated.Methods CHA with different mass fractions was encapsulated in mesoporous silica nanoparticles (MSNs) (denoted CHA@MSNs). Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) were used to characterize the samples. The 3M Z350XT flow resin was divided into 4 groups: group A: 3M+CHA@MSNs (0%); group B: 3M+CHA@MSNs (3%); group C: 3M+CHA@MSNs (5%); and group D: 3M+CHA@MSNs (6.4%), with mass scores of 0%, 3%, 5%, and 6.4%, respectively. The shear strength of the modified adhesive was tested by a universal electronic material testing machine, the adhesive residue was observed by a 10 × magnifying glass, and the adhesive Remnant index (ARI) was calculated. The four groups of modified adhesives were cultured with Streptococcus mutans. The OD540 value of the bacterial solution was measured by a spectrophotometer, and the amount of plaque attachment was observed by scanning electron microscopy to evaluate the antibacterial performance of the adhesives.Results Infrared spectroscopic analysis of CHA@MSNs showed that CHA was successfully loaded onto MSNs. Under scanning electron microscopy, it could be seen that, after Cha was combined with MSNs, the structure of MSNs changed, as the boundary was fuzzy and aggregated into a layered structure. A comparison of shear strength revealed a statistically significant difference between the groups containing CHA@MSNs and the groups without CHA@MSNs (P 0.05). There was no statistical significance across all groups (P > 0.05), suggesting that the addition of CHA@MSNs had little effect on the bracket shedding. The OD540 value of bacterial fluid indicated that the difference among groups A, B and C was statistically significant (P < 0.05), and the antibacterial effect of group C was the best; there was no statistically significant difference between group C and group D (P > 0.05).Conclusions Therefore, adding 5% CHA@MSN antibacterial agent significantly improved the antibacterial effect and did not affect the bond strength.

Abstract Objective To retrospectively analyze the short and long-term efficacies of O-arm-navigated percutaneous short segment pedicle screw fixation, with or without screwing of the fractured vertebra. Methods A total of 42 patients who underwent O-arm-navigated percutaneous short segment pedicle screw fixation for the treatment of thoracolumbar fractures from February 2015 to December 2018 were selected for analysis. The patients were divided into two groups according to the surgical intervention they received: Group A received percutaneous short segment pedicle screw fixation with screwing of the fractured vertebra and Group B received percutaneous short segment pedicle screw fixation without screwing of the fractured vertebra. Radiographic analysis included Cobb angles and percentage of anterior vertebral height (AVH%). Clinical functional outcomes were assessed using the visual analog scale (VAS) for back pain and the oswestry disability index (ODI) scores. Results No significant differences were observed in the operation time and intraoperative blood loss between the two groups (P > 0.05). The length of incision was statistically significantly different between the two groups (P 0.05). However, the Cobb angle and AVH% were both significantly larger in Group A than Group B at the final follow-up (P 0.05). Conclusion In the short term, both minimally invasive treatments were safe and effective in treating thoracolumbar fracture. Although there was significant difference between the two groups in Cobb angle and vertebral body height at the last follow-up, the difference was small. Therefore, these specific parameters will be an important outcome measure in further investigations.

Abstract We used optical coherence tomography (OCT) to analyze the "half-moon" like phenomenon and its characteristics and observe 1-year follow-up of the in-stent restenosis (ISR) incidence after the drug eluted stent (DES) implantation in patients with the myocardial bridge (MB). Patients were retrospectively analyzed from January 2013 to December 2019. We used OCT to check 45 patients with MB and found a visible muscle layer (VML) around the vessel adventitia with the same or high density compared to the vessel media layer. There was not any significant difference in maximal thickness, maximal arch, and total length between the half-moon layer and the visible muscle layer groups (p > 0.05). Maximal thickness, arch, and total length of the half-moon layer were significantly positively related to VML, respectively (r = 0.962, 0.985, 0.742, p 0.05). OCT could evaluate MB characteristics accurately compared to IVUS and had a higher rate of detecting MB than CAG. Moreover, it is safe and effective to guide DES covering the mild MB segment in patients with severe coronary lesions detected by the OCT.

Abstract Background The unique mechanism of diabetic atherosclerosis has been a central research focus. Previous literature has reported that the inflammatory response mediated by dendritic cells (DCs) plays a vital role in the progression of atherosclerosis. The objective of the study was to explore the role of DCs in diabetes mellitus complicated by atherosclerosis. Methods ApoE−/− mice and bone marrow-derived DCs were used for in vivo and in vitro experiments, respectively. Masson’s staining and Oil-red-O staining were performed for atherosclerotic lesion assessment. The content of macrophages and DCs in plaque was visualized by immunohistochemistry. The expression of CD83 and CD86 were detected by flow cytometry. The fluctuations in the RNA levels of cytokines, chemokines, chemokine receptors and adhesions were analyzed by quantitative RT-PCR. The concentrations of IFN-γ and TNF-α were calculated using ELISA kits and the proteins were detected using western blot. Coimmunoprecipitation was used to detect protein–protein interactions. Results Compared with the ApoE−/− group, the volume of atherosclerotic plaques in the aortic root of diabetic ApoE−/− mice was significantly increased, numbers of macrophages and DCs were increased, and the collagen content in plaques decreased. The expression of CD83 and CD86 were significantly upregulated in splenic CD11c+ DCs derived from mice with hyperglycemia. Increased secretion of cytokines, chemokines, chemokine receptors, intercellular cell adhesion molecule (ICAM), and vascular cell adhesion molecule (VCAM) also were observed. The stimulation of advanced glycation end products plus oxidized low-density lipoprotein, in cultured BMDCs, further activated toll-like receptor 4, protein kinase C and receptor of AGEs, and induced immune maturation of DCs through the RAGE-TLR4-PKCβ1 signaling pathway that was bound together by intrinsic structures on the cell membrane. Administering LY333531 significantly increased the body weight of diabetic ApoE−/− mice, inhibited the immune maturation of spleen DCs, and reduced atherosclerotic plaques in diabetic ApoE−/− mice. Furthermore, the number of DCs and macrophages in atherosclerotic plaques was significantly reduced in the LY333531 group, and the collagen content was increased. Conclusions Diabetes mellitus aggravates chronic inflammation, and promotes atherosclerotic plaques in conjunction with hyperlipidemia, which at least in part through inducing the immune maturation of DCs, and its possible mechanism of action is through the RAGE-TLR4-pPKCβ1 signaling pathway.

Objective To explore a new pathway of otorhinolaryngology training which combines medicine and humanity and made balance between the two systems. Methods The content of humanity and history was added into the classic courseware and class discussion. Then the effects of this new model were evaluated using a system for evaluation of otolaryngology teaching qualities. Results Otorhinolaryngology training with the new model was highly applauded by students, especially in the aspects of innovation and motivation. Improvements were needed for anatomy and the class atmosphere. Conclusions Combination of medicine and humanity motivates the students a lot and build their consciousness of humanity, which facilitates their self-regualted learning. This new education model is worth more promotion and popularization.