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Abstract Background Pancreatic cancer-associated fibroblasts (CAFs) play a crucial role in tumor progression and immune evasion. Asperuloside (ASP) is an iridoid glycoside with potential anti-tumor properties. This study aimed to explore the molecular mechanisms of ASP on CAFs, particularly focusing on its effects on activating transcription factor 6 (ATF6), a key regulator of endoplasmic reticulum stress. Method CAFs were treated with different concentrations of ASP (0, 1, 3, and 5 mM), and the role of ATF6 was investigated by over-expressing it in CAFs. Subsequently, western blot was used to detect ATF6, α-smooth muscle actin (α-SMA), fibroblast activating protein (FAP), and vimentin protein levels in CAFs. The collagen gel contraction assay and Transwell assay were applied to evaluate the contraction and migration ability of CAFs. In addition, the interleukin (IL)-6, C–C motif chemokine ligand (CCL)-2, and C-X-C motif chemokine ligand (CXCL)-10 levels were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results CAFs had significantly higher expression levels of α-SMA, FAP, and vimentin compared to normal fibroblasts (NFs). ASP significantly inhibited the activation, contraction, and migration of CAFs in a concentration-dependent manner. ASP treatment also reduced the expression of cytokines (IL-6, CCL2, and CXCL10) and down-regulated ATF6 levels. Over-expression of ATF6 mitigated the inhibitory effects of ASP. Conclusion ASP exerts its anti-tumor effects by down-regulating ATF6, thereby inhibiting the activation and function of pancreatic CAFs. These findings suggest that ASP could be a promising therapeutic agent for pancreatic cancer by modulating the tumor microenvironment.

Abstract Currently approved HER2-targeting antibody-drug conjugates (ADCs) for HER2-positive breast cancer (BC) are associated with safety concerns. In this multicenter, single-arm, dose-escalation (phase 1a) and dose-expansion (phase 1b) phase 1 trial (NCT03944499), patients with HER2-expressing advanced solid tumors received FS-1502 (an anti-HER2 ADC) with a 3 + 3 design in phase 1a; patients with metastatic HER2-positive BC received FS-1502 at the recommended phase 2 dose (RP2D) in phase 1b. The primary end points were dose-limiting toxicities (DLTs), maximum tolerated dose (MTD) and RP2D for phase 1a and objective response rate (ORR) for phase 1b. A total of 150 patients with HER2-expressing solid tumors (n = 5) and BC (n = 145) were enrolled (female, n = 146, 97.3%). One DLT each was reported at 3.0 and 3.5 mg/kg; the MTD was not reached. The RP2D was 2.3 mg/kg once every 3 weeks. Five (3.3%) patients experienced pneumonitis; four (2.7%) had grade 3 reversible ocular events. Of 67 HER2-positive BC patients receiving the RP2D, the best ORR was 53.7% (95% CI, 41.1-66.0%), including PRs confirmed (confirmed ORR, 37.5%) and pending for confirmation. FS-1502 was well tolerated with limited ocular and pulmonary findings and demonstrated promising antitumor activity in HER2-positive BC patients.

In search of innovative antifungal solutions for the control of plant diseases, a series of cyanoacrylate derivatives containing naphthalene groups were designed and synthesized, and their inhibition activity against four plant pathogenic fungi was evaluated. The results of in vitro bioassay revealed that some target compounds possessed obvious antifungal effect against Fusarium graminearum. As the most prominent one, compound A2 showed a inhibition rate of 98.46 % at 10 µg/mL and an EC50 value of 0.26 µg/mL, which was close to that of the positive control phenamacril (with a inhibition rate of 100 % at 10 µg/mL and EC50 value of 0.14 µg/mL). The compound A2 also markedly inhibited the growth of F. graminearum inoculated on rice leaves at 200 μg/mL with the protective and curative efficiencies of 89.03 % and 90.91 %, respectively, which were close to that of the positive control phenamacril (with the protective and curative efficiencies of 94.54 % and 96.36 %, respectively). The observation under scanning electron microscopy and measurement of relative conductivity revealed that compound A2 caused the hyphal surface become shrunken and rough, and made the cell membrane permeability increased. Molecular docking and molecular dynamics simulation analyses showed that compound A2 interacted with the key residues in the active site of myosin-5 in a similar mode as phenamacril. These results suggested that target compounds were potential myosin-5 inhibitors, they could serve as the lead compounds for further structural optimization to develop new fungicides against F. graminearum.

Background: High circulatory lipoprotein(a) [Lp(a)] concentration promotes atherosclerosis; however, its efficacy in predicting the extent of atherosclerotic coronary heart disease (CHD) with coronary artery obstruction and major adverse cardiovascular events (MACEs) in diabetic patients remains questionable. This study aimed to examine whether elevated circulating Lp(a) levels exacerbate CHD and to assess their utility in predicting MACEs in individuals diagnosed with type 2 diabetes mellitus (T2DM). Methods: In total, 4332 patients diagnosed with T2DM who underwent coronary angiography (CAG) were included and categorized into two groups (CHD and non-CHD) based on the CAG results. We used a correlation analysis to explore the potential links between the levels of circulating Lp(a) and CHD severity. Cox regression analysis was performed to evaluate MACEs. Results: The concentrations of circulating Lp(a) were markedly elevated in the CHD group and positively correlated with disease severity. Our results indicate that elevated circulating Lp(a) is a crucial risk factor that significantly contributes to both the progression and severity of CHD. The differences between the two groups are evident in the risk of CHD occurrence [odds ratio (OR) = 1.597, 95 % confidence interval (CI): 1.354–1.893, p

Public cell culture platform is an important facility in laboratory animal facilities, providing essential support for scientific research such as the development of animal tumor disease models and transgenic animals. By establishing a public cell culture experimental platform, laboratory animal centers can effectively integrate experimental animals and cell culture resources, optimizing the allocation of scientific research resources to facilitate better research outcomes. The majority of cells cultured in these platforms are used for animal experiments. Contamination or quality issues in these cells not only affect experimental results but also jeopardize the health of experimental animals, potentially leading to microbial infections and contamination of entire animal facilities. Therefore, public cell culture laboratories within experimental animal facilities impose stricter quality control measures than conventional cell culture rooms. This study takes the public cell culture platform at the Laboratory Animal Center of Shanghai Jiao Tong University as a case study to discuss management experiences, focusing on facility maintenance and management, personnel management and quality control of cell biological risk. The aim is to provide useful reference for the management of public cell culture laboratories in experimental animal facilities and other institutions.

Abstract Background Laparoscopic surgery has been endorsed by clinical guidelines for colon cancer, but not for rectal cancer on account of unapproved oncologic equivalence with open surgery. Aims We started this largest‐to‐date meta‐analysis to comprehensively evaluate the safety and efficacy of laparoscopy in the treatment of rectal cancer compared with open surgery. Materials & Methods Both randomized and nonrandomized controlled trials comparing laparoscopic proctectomy and open surgery between January 1990 and March 2020 were searched in PubMed, Cochrane Library and Embase Databases (PROSPERO registration number CRD42020211718). The data of intraoperative, pathological, postoperative and survival outcomes were compared between two groups. Results Twenty RCTs and 93 NRCTs including 216,615 patients fulfilled the inclusion criteria, with 48,888 patients received laparoscopic surgery and 167,727 patients underwent open surgery. Compared with open surgery, laparoscopic surgery group showed faster recovery, less complications and decreased mortality within 30 days. The positive rate of circumferential margin (RR = 0.79, 95% CI: 0.72 to 0.85, p

Introduction: Urban resilience is suffering from the challenges of climate change. The increasing volatility of climate change and its impact on urban resilience necessitates a deeper understanding of how internal organizational behaviors can contribute toward sustainable city development. Pro-environmental behavior is one of the important methods of affecting climate change and enhancing urban resilience. This study investigates how employee participation in corporate social responsibility activities promotes pro-environmental behavior and its mechanism.Methods: This research was conducted an online survey of 262 employees from 22 industries in mainland China. To mitigate the bias arising from self-reported assessments by the employees, the data were collected at two time points.Results: Empirical research reveals that employee participation in corporate social responsibility is positively related to employee pro-environmental behavior; these empirical findings not only support how psychological ownership mediates the link between corporate social responsibility participation and pro-environmental behavior but also indicate how employee engagement acts as an intermediary mechanism in enhancing this positive association. Moreover, the chain mediation effect of psychological ownership and employee engagement in the positive link between corporate social responsibility participation and pro-environmental behavior is found to be significant.Discussion: These findings not only enrich the effects of the mechanism of corporate social responsibility participation on employee behavior by introducing new theoretical perspectives but also deepen understanding of the antecedents promoting employee pro-environmental behavior, thereby contributing to the improvement of urban resilience in the face of climate change.

Abstract Micro-sized silicon anodes can significantly increase the energy density of lithium-ion batteries with low cost. However, the large silicon volume changes during cycling cause cracks for both organic-inorganic interphases and silicon particles. The liquid electrolytes further penetrate the cracked silicon particles and reform the interphases, resulting in huge electrode swelling and quick capacity decay. Here we resolve these challenges by designing a high-voltage electrolyte that forms silicon-phobic interphases with weak bonding to lithium-silicon alloys. The designed electrolyte enables micro-sized silicon anodes (5 µm, 4.1 mAh cm−2) to achieve a Coulombic efficiency of 99.8% and capacity of 2175 mAh g−1 for >250 cycles and enable 100 mAh LiNi0.8Co0.15Al0.05O2 pouch full cells to deliver a high capacity of 172 mAh g−1 for 120 cycles with Coulombic efficiency of >99.9%. The high-voltage electrolytes that are capable of forming silicon-phobic interphases pave new ways for the commercialization of lithium-ion batteries using micro-sized silicon anodes.

Extracts of Stevia rebaudiana Bertoni plant leaves contain a mixture of diterpene glycosides which possess high sweetness and are used as non-caloric sweeteners in foods and beverages. One of the most abundant of these steviol glycosides is Rebaudioside C (Reb C), which bears one esterified β-D-glucose and one glycosidically linked α-L-rhamnosyl-(1→2)-[β-D-glucosyl-(1→4)]-D-glucose trisaccharide. In this work, we isolated Reb C from commercial Stevia extracts using an orthogonal normal-phase × reversed-phase purification strategy. We then demonstrated that Reb C could be used as a donor substrate for enzymatic trans glycosylation reactions using chemically synthesized 1-deoxy-1-fluoro-D-glucose and 1-deoxy-1-fluoro-D-galactose donors and two engineered glycosynthases derived from Agrobacterium and Streptomyces β-glycosidases. This chemoenzymatic glucosylation/galactosylation strategy may be of use to extend the current repertoire of steviol glycosides analogues for analysis or the sensory evaluation of these novel steviol glycosides.

Abstract Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay. Correlation and logistic regression analyses were performed to investigate the association between PCSK9 expression and CHD severity. This study used Cox regression analysis to assess the association between circulating PCSK9 levels and the risk of MACEs. Results Circulating PCSK9 levels were significantly higher in the CHD group than in the non-CHD group [554.62 (265.11) ng/mL vs. 496.86 (129.05) ng/mL, p

AbstractContext Atopic dermatitis (AD) is a common inflammatory skin disease characterized with hyperactivation of type 2 T helper (Th2) immune responses. Icariin is a flavonoid glucoside with anti-inflammatory activities, which has been used to treat multiple diseases.Objective The present study investigates the underlying mechanisms by which icariin regulates Th2 responses and AD development.Materials and methods BALB/c mice were induced by DNFB to establish AD models, and injected with or without 10 mg/kg icariin for 2 weeks (i.p., daily). CD4+T cells were induced by Th2 condition to simulate AD in vitro, and also treated with or without 100 µM icariin.Results Icariin ameliorated AD-like skin lesion, manifested as a significant decrease in dermatitis scores (from 8.00 ± 1.00 to 3.67 ± 0.58), serum IgE levels (from 3119.15 ± 241.81 to 948.55 ± 182.51 ng/mL), epidermal thickness (from 93.86 ± 4.61 to 42.67 ± 2.48 µm) and infiltration of mast cells (from 60.67 ± 3.21 cells to 36.00 ± 2.65 cells). Also, icariin inactivated NLRP3 inflammasome, inhibited Th2 skewing, reduced lncRNA MALAT1 expression, but elevated miR-124-3p expression in vivo and in vitro. MALAT1 increased NLRP3 expression through targeting miR-124-3p. Knockdown of MALAT1 repressed NLRP3 inflammasome activation and mitigated Th1/Th2 imbalance in Th2-conditioned CD4+T cells, whereas both MALAT1 overexpression and miR-124-3p inhibition ablated the inhibitory effects of icariin on Th2 immune responses.Discussion and conclusions The findings further improve our understanding of the mechanism by which icariin affects AD progression, and highlights the potential of icariin in the treatment of AD.

Abstract Background and Objectives This study was conducted to investigate the effect of high-fat meals on the pharmacokinetics (PK) and safety profile of SAF-189s, a novel ALK/ROS1 inhibitor. Methods This was a single-center, phase I, open-label, crossover study in which healthy adults (≥18 years) were randomized (1:1) to two sequences of SAF-189s administration (fasted-fed or fed-fasted) separated by a 14-day washout. After a ≥10-h overnight fast, volunteers received SAF-189s 160 mg orally in a fasted state or 30 min after a high-fat, high-calorie meal. Similarity of pharmacokinetic parameters was concluded if the 90% CI for the geometric mean ratio (GMR) between the fed and fasted group fell within the predefined range of 0.80–1.25. Results In total, 24 subjects were enrolled and 23 completed the study. SAF-189s maximum plasma concentration (C max; GMR: 109.1% [90% CI 103.1–115.4]) was comparable under fed (high-fat meal, n = 24) versus fasted (n = 23) conditions, with no effect on area under the plasma concentration–time curve from time 0 to t (AUC0-t; GMR: 105.1% [90% CI 100.3–110.2]) and AUC from time 0 to infinity (AUC0-∞; GMR: 105.5% [90% CI, 100.6–110.6]). In both groups, the median time to maximum plasma concentration (t max) was around 6 h and mean plasma half-life (t ½) was around 35 h. Fed administration led to a lower incidence of treatment-emergent adverse events (TEAEs; 29.2% vs 54.2%), including gastrointestinal disorders (4.2% vs 41.7%) and headache (0.0% vs 12.5%), versus fasted administration. Conclusions A high-fat meal had minimal effect on the pharmacokinetic profile of SAF-189s compared with a fasted state following a single dose of 160 mg. Administration with a high-fat meal led to a lower incidence of TEAEs.

AIM: To investigate the changes and correlation of retinal nerve fiber layer(RNFL)and macular retinal thickness in children with anisometropic amblyopia.METHODS: A total of 159 cases(159 eyes)children with anisometropic amblyopia treated in our ophthalmology department from October 2020 to June 2021 were selected as the study group, and 159 cases(159 eyes)children with normal vision who examined in the ophthalmology department of our hospital in the same period and age group were selected as the control group. The study group received traditional comprehensive training combined with 4D visual training for amblyopia based on refractive correction and covering of healthy eyes. The RNFL and macular retinal thickness before and after treatment between the study group and the control group was compared, and the correlation between RNFL and macular retinal thickness before treatment in the study group was analyzed.RESULTS: The RNFL thickness of average, upper, lower, nasal and temporal in the study group before and after 3mo of treatment was higher than those of the control group, and the RNFL thickness of average, upper, lower, nasal and temporal before treatment in the study group was higher than those after 3mo of treatment(P

This study investigated the distribution of sedimentary phosphorus (P) species along an area of a rapid current at the southern coast of Zhoushan Island. The objective of this study was to improve the understanding of P cycling in a zone of rapid water cycling. Results showed that the average percentage of each P form to total P (TP) was in the following order: apatite P (Ca-P; 52%) was found in the most abundant, followed by organic P (OP; 16%), exchangeable-P (Ex-P; 14%), detrital P (De-P; 11%), and iron-bound P (Fe-P; 7%). Ca-P showed a trend of an increasing concentration from a location at the west (ZS1 has mean Ca-P = 45.6 mg kg−1) toward the east (ZS2 has mean Ca-P = 82.69 mg kg−1) and south-east (ZS3 has mean Ca-P = 82.17 mg kg−1); De-P also increased from 15.12 mg kg−1 at ZS1 to 22.53 mg kg−1 at ZS2 and 27.45 mg kg−1 at ZS3, but the three bioavailable P species, OP, Ex-P, and Fe-P, decreased from the west toward the east of the coastal area. Results along the cores showed the occurrences of sediment P adsorption and release throughout the time span from the 1930s to the present, with an overall trend of decreasing Ca-P and TP from the bottom to surface sediments. There was a tendency of Ca-P formation at the expense of Ex-P and OP release during transport and organic matter decomposition. The likely impact of climate change in the coastal zone would be an increased temperature resulting in elevated organic matter decomposition and P release.

As an important part of die steels, hot-work die steels are mainly used to manufacture molds made of solid metal or high-temperature liquid metal from heating to recrystallization temperature. In view of the requirements for mechanical properties and service life for hot-work die steel, it is conducive to improve the thermal fatigue resistance, wear resistance, and oxidation resistance of hot work die steel. In this review, the main failure modes of hot-work die steel were analyzed. Four traditional methods of strengthening and toughening die steel were summarized, including optimizing alloying elements, electroslag remelting, increasing the forging ratio, and heat treatment process enhancement. A new nano-strengthening method was introduced that aimed to refine the microstructure of hot-work abrasive steel and improve its service performance by adding nanoparticles into molten steel to achieve uniform dispersion. This review provides an overview to improve the service performance and service life of hot work die steel.

Abstract Introduction Psittacosis can cause severe community-acquired pneumonia (CAP). The clinical manifestations of psittacosis range from subclinical to fulminant psittacosis with multi-organ failure. It is essential to summarize the clinical characteristic of patients with severe psittacosis accompanied by acute hypoxic respiratory failure (AHRF). Methods This retrospective study included patients with severe psittacosis caused CAP accompanied by AHRF from 19 tertiary hospitals of China. We recorded the clinical data, antimicrobial therapy, respiratory support, complications, and outcomes. Chlamydia psittaci was detected on the basis of metagenomic next-generation sequencing performed on bronchoalveolar lavage fluid samples. Patient outcomes were compared between the treatment methods. Results This study included 45 patients with severe CAP and AHRF caused by psittacosis from April 2018 to May 2021. The highest incidence of these infections was between September and April. There was a history of poultry contact in 64.4% of the patients. The median PaO2/FiO2 of the patients was 119.8 (interquartile range, 73.2 to 183.6) mmHg. Four of 45 patients (8.9%) died in the ICU, and the median ICU duration was 12 days (interquartile range, 8 to 21) days. There were no significant differences between patients treated with fluoroquinolone initially and continued after the diagnosis, fluoroquinolone initially followed by tetracycline, and fluoroquinolone combined with tetracycline. Conclusion Psittacosis caused severe CAP seems not rare, especially in the patients with the history of exposure to poultry or birds. Empirical treatment that covers atypical pathogens may benefit such patients, which fluoroquinolones might be considered as an alternative.

This study examines the impact of the Latin American Integrated Market (MILA for its Spanish acronym) on investment efficiency from 2003 to 2020. Our research suggests that MILA affects the efficiency of investment decisions by reducing information asymmetry and the agency problem. We present compelling empirical evidence that the impact of MILA on enhancing investment efficiency is especially pronounced in the over-investment problem. Furthermore, the mediation analysis reveals that firms listed on MILA stock exchanges have increased the efficiency of their investments, a result attributable partly to enhanced financial reporting quality. We employ difference-in-difference analysis to address the possibility of endogeneity. Our findings are validated by the fact that, compared with control firms, treatment firms improve their investment efficiency and mitigate the over-investment problem, thereby validating our findings.

In this reported study, the density functional theory (DFT) was used at the (U)B3LYP/6-311G(d,p) level to investigate the stabilization process of the nitrate ester plasticized polyether propellant (NEPE). Molecular simulations were conducted of the reaction that generates NO2, the autocatalytic and aging reaction triggered by the NO2, and the nitrogen dioxide absorption reaction of the stabilizers during the propellent stabilization process. These simulations were derived using the transition-state theory (TST) and variational transition-state theory (VTST). The simulation results suggested that the stabilization of the NEPE propellant consisted of three stages. First, heat and NO2 were generated during the denitrification reaction of nitroglycerine (NG) and 1,2,4-butanetriol trinitrate(BTTN) in the NEPE propellant. Second, nitroso products were generated by the reactions of N-Methyl-4-nitroaniline (MNA) and 2-nitrodiphenylamine (2NDPA) with NO2. Third, the stabilizers were exhausted and the autocatalytic reaction of NG and BTTN and the aging reaction of polyethylene glycol (PEG) were triggered by the heat and NO2 generated in the first stage. By comparing the energy barriers of the various reactions, it was found that the NO2 generated from the denitrification reaction significantly reduced the reaction energy barrier to 105.56–126.32 kJ/mol, also increased the reaction rate constant, and decreased the thermal stability and energetic properties of the NEPE propellant. In addition, the NO2 also weakened the mechanical properties of the NEPE propellant by attacking the –CH2 groups and the O atoms in the PEG molecular chain. The energy barriers of the reactions of MNA and 2NDPA with NO2 (94.61–133.61 kJ/mol) were lower than those of the autocatalytic and decomposition reactions of NG, BTTN, and the aging reactions of PEG (160.30–279.46 kJ/mol). This indicated that, by eliminating NO2, the stabilizer in the NEPE propellant can effectively prevent NO2 from reacting with the NG, BTTN, and PEG in the NEPE propellant. Consequently, this would help maintain the energy and mechanical properties of the NEPE propellant, thereby improving its thermal stability.

Abstract Background Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN. Methods This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles. Results Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug–related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing. Conclusions FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication. Trial registration ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

Natural and geological environmental conditions have an important impact on the planning and construction of sponge cities. This paper analyzes geological factors that influence the usage of natural sponge bodies, taking the Shuanghe lake district of Zhengzhou airport zone as an example. An evaluation system with seven factors has been established and the weights of these factors are determined using the analytic hierarchy process (AHP) method. Overlay analysis is then carried out on all factors using GIS to evaluate the geological suitability of the construction of the sponge city. The results show that geologically suitable area for city construction in Shuanghe lake district accounts for 12.3%, relatively suitable area accounts for 76.1%, and relatively unsuitable area accounts for 11.6%. For suitable and relatively suitable areas, we should make full use of the advantages of surface infiltration, vadose zone transportation and aquifer storage to build a sponge city infrastructure with geological engineering as the main component, supplemented by engineering measures such as surface water storage and drainage, and jointly establish a sustainable urban hydrological cycle. For less suitable areas, artificial rain and flood control works, such as roof garden, should be considered. The findings of this paper can serve as an important reference for sponge city planning and construction not only in the research area but also in other regions with similar geological conditions.

Background. Tenapanor is a locally acting selective sodium-hydrogen exchanger 3 inhibitor with the potential to treat sodium/phosphorus and fluid overload in various cardiac-renal diseases, which has been approved for constipation-predominant irritable bowel syndrome in the US. The pharmacokinetics (PK) of tenapanor and its metabolite tenapanor-M1 (AZ13792925), as well as the safety and tolerability of tenapanor, were investigated in healthy Chinese and Caucasian subjects. Methods. This randomized, open-label, single-center, placebo-controlled phase 1 study (https://www.chinadrugtrials.org.cn; CTR20201783) enrolled Chinese and Caucasian healthy volunteers into 4 parallel cohorts (3 cohorts for Chinese subjects, 1 cohort for Caucasian subjects). In each cohort, 15 subjects were expected to be included and received oral tenapanor (10 or 30 mg as single dose, or 50 mg as a single dose followed by a twice-daily repeated dose from Day 5 to 11, with a single dose in the morning on Day 11) or placebo in a 4 : 1 ratio. Results. 59 healthy volunteers received tenapanor 10 mg (n = 12 Chinese), 30 mg (n = 12 Chinese), or 50 mg (n = 12 (Chinese), n = 11 (Caucasian)) or placebo (n = 12, 3 per cohort). After single and twice-daily repeated doses, tenapanor plasma concentrations were all below the limit of quantitation; tenapanor-M1 appeared slowly in plasma. In single-ascending dose evaluation (10 to 50 mg) of Chinese subjects, the mean Cmax, AUC0-t, and AUC0-∞ of tenapanor-M1 increased with increasing dose level, and AUC0-t increased approximately dose proportionally. The Cmax accumulation ratio was 1.55 to 6.92 after 50 mg repeated dose in Chinese and Caucasian subjects. Exposure to tenapanor-M1 was generally similar between the Chinese and Caucasian subjects. Tenapanor was generally well-tolerated and the safety profile was similar between the Chinese and Caucasian participants receiving tenapanor 50 mg, as measured by vital signs, physical and laboratory examination, 12-lead ECG, and adverse events. No serious adverse event or adverse event leading to withdrawal occurred. Conclusion. Tenapanor was well-tolerated, with similar PK and safety profiles between Chinese and Caucasian subjects. This trial is registered with CTR20201783.

Background: Neurodegenerative retinal diseases such as retinitis pigmentosa are serious disorders that may cause irreversible visual impairment. Ferroptosis is a novel type of programmed cell death, and the involvement of ferroptosis in retinal degeneration is still unclear. This study aimed to investigate the related ferroptosis genes in a mice model of retinal degeneration induced by light damage. Methods: A public dataset of GSE10528 deriving from the Gene Expression Omnibus database was analyzed to identify the differentially expressed genes (DEGs). Gene set enrichment analysis between light damage and control group was conducted. The differentially expressed ferroptosis-related genes (DE-FRGs) were subsequently identified by intersecting the DEGs with a ferroptosis genes dataset retrieved from the FerrDb database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were further performed using the DE-FRGs. A protein-protein interaction (PPI) network was constructed to identify hub ferroptosis-related genes (HFRGs). The microRNAs (miRNAs)-HFRGs, transcription factors (TFs)-HFRGs networks as well as target drugs potentially interacting with HFRGs were analyzed utilizing bioinformatics algorithms. Results: A total of 932 DEGs were identified between the light damage and control group. Among these, 25 genes were associated with ferroptosis. GO and KEGG analyses revealed that these DE-FRGs were mainly enriched in apoptotic signaling pathway, response to oxidative stress and autophagy, ferroptosis, necroptosis and cytosolic DNA-sensing pathway. Through PPI network analysis, six hub ferroptosis-related genes (Jun, Stat3, Hmox1, Atf3, Hspa5 and Ripk1) were ultimately identified. All of them were upregulated in light damage retinas, as verified by the GSE146176 dataset. Bioinformatics analyses predicated that 116 miRNAs, 23 TFs and several potential therapeutic compounds might interact with the identified HFRGs. Conclusion: Our study may provide novel potential biomarkers, therapeutic targets and new insights into the ferroptosis landscape in retinal neurodegenerative diseases.

Chronic obstructive pulmonary disease (COPD) is a complex, heterogeneous respiratory disease that is characterized by functional and structural alterations mainly caused by long-term inhalation of harmful particles. Cigarette smoke (CS) is a major risk factor for COPD. Inflammation, cellular stress, and tissue damage caused by cigarette smoke play key roles in COPD progression. Extracellular vesicles (EVs) are functional nanoscale membrane-bound vesicles. Recently, EVs have attracted more and more attention due to their roles in the diagnosis and treatment of many diseases. However, the research on the roles and mechanism of EVs in smoking-induced COPD is still in its infancy. In this paper, we provided an overview of national and international research on the roles and mechanisms of EVs in the pathogenesis of CS-induced COPD.

Cadmium (Cd) exerts a toxic influence on numerous crucial growth and development processes in plants, notably affecting seed germination rate, transpiration rate, chlorophyll content, and biomass. While considerable advances in Cd uptake and detoxification of plants have been made, the mechanisms by which plants adapt to and tolerate Cd toxicity remain elusive. This review focuses on the relationship between Cd and plants and the prospects for phytoremediation of Cd pollution. We highlight the following issues: (1) the present state of Cd pollution and its associated hazards, encompassing the sources and distribution of Cd and the risks posed to human health; (2) the mechanisms underlying the uptake and transport of Cd, including the physiological processes associated with the uptake, translocation, and detoxification of Cd, as well as the pertinent gene families implicated in these processes; (3) the detrimental effects of Cd on plants and the mechanisms of detoxification, such as the activation of resistance genes, root chelation, vacuolar compartmentalization, the activation of antioxidant systems and the generation of non-enzymatic antioxidants; (4) the practical application of phytoremediation and the impact of incorporating exogenous substances on the Cd tolerance of plants.

Solid biomass can be used for energy generation and the production of various renewable bioproducts. The aim of this study was to determine the yield and characteristics of wood obtained as debarking residue from 14 genotypes of short-rotation woody crops (SRWCs). These included five Populus genotypes, one Robinia genotype, and eight Salix genotypes, harvested in both annual and quadrennial cycles. The results showed that the highest dry wood yield (12.42 Mg ha−1 y−1 DM) and yield energy value (244.34 GJ ha−1 y−1) were obtained from willow (cultivar Żubr) harvested in a quadrennial cycle. The best effect among the poplar genotypes was achieved for the Hybryda275, and it was particularly marked in the quadrennial harvest cycle. The poorest results were determined for black locust. The Robinia characteristics included the significantly lowest moisture content (31.6%), which was a positive attribute from the energy point of view, but, on the other hand, it had some adverse characteristics—the highest levels of sulfur (0.033% DM), nitrogen (0.38% DM), and ash (0.69% DM). More beneficial properties in this respect were determined for willow and poplar wood. Moreover, willow and poplar wood contained more cellulose—51.8 and 50.0% DM, respectively—compared with black locust. Extending the SRWC shoot harvest cycle from annual to quadrennial resulted in an increase in cellulose, lignin, and carbon, higher heating value, and a decrease in nitrogen, sulfur, ash, and moisture content. Therefore, extending the harvest cycle improved the parameters of SRWC wood as an energy feedstock.

Because the temperature has a great influence on the assimilation reaction speed, only the assimilation parameters of iron ore powder cannot compare the assimilation difference of different iron ore powder. In order to express the influence of temperature on the assimilation reaction speed, it is necessary to establish the relationship between temperature and reaction speed. The melting process of iron ore powder is transformed into its data information. There is a relationship between different factors of iron ore powder and time in the process of high temperature melting, which makes a theoretical basis for real-time understanding of iron ore powder in melting. Firstly, the Faster R-CNN(Regions with CNN features) algorithm is used to identify the target image, and then use traditional segmentation algorithm, SVM (support vector machine) algorithm and improved SVM algorithm to segment the image. The optimal algorithm is analyzed by similarity with the original image. Secondly, the area and volume are selected as the indicators of edge contour characteristics. This study shows that the SVM algorithm segmentation after adding the data set can segment the iron ore powder more clearly, and the fitting curves of area, volume, time and temperature can be obtained. These two indicators can be used to characterize the melting process of iron ore powder, estimate the actual melting rate of iron ore powder and study its assimilation in real time. The assimilation reaction performance of iron ore powder can be reflected more comprehensively by calculating the characteristic number of assimilation reaction.

Objective: To improve the yield and antibacterial rate of antimicrobial peptides from Pleurotus tuber-regium mycelium （PTRM-AMPs）. Methods: Taking the yield and the antibacterial rate of PTRM-AMPs against Staphylococcus aureus and Escherichia coli as evaluation indexes, on the basis of protease screening, the extraction process of PTRM-AMPs was optimized, and the minimum inhibitory concentration of PTRM-AMPs was determined. Results: The optimum technological conditions for the preparation of PTRM-AMPs by alkaline protease hydrolysis were as follows: the enzymatic hydrolysis temperature was 39.5 ℃, the enzymatic hydrolysis time was 3.2 h, the pH value was 11.1, the solid-liquid ratio was 1∶20 （g/mL）, and the enzyme addition was 6 000 U/g. Under these conditions, the actual antibacterial rates of PTRM-AMPs against S. aureus and E. coli were 74.17% and 86.22% respectively, and the yield of PTRM-AMPs was 22.67%. The MIC values of PTRM-AMPs against S. aureus and E. coli were 5.0, 2.5 mg/mL respectively. Conclusion: PTRM-AMPs has significant antibacterial activity, especially against E. coli.

Municipal solid waste incinerator (MSWI) not only is deemed one of the uppermost sources of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), but also produces substantial amount of polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) owing to the existence of brominated flame retardants (BFRs) in the waste. So far, however, PBDD/Fs in the vicinal environments of MSWI and their associated risks remain rarely studied. Based on a one-year passive air sampling (PAS) scheme, we investigated airborne PBDD/Fs and PCDD/Fs around a large-scale MSWI that has been operated for multi-years. Both the concentrations of PBDD/Fs and PCDD/Fs showed spatially decreasing trends with the distance away from the MSWI, confirming the influence of the MSWI on the dioxin levels in its ambient air. But its influence on PBDD/Fs was less because PBDD/Fs exhibit lower volatility and therefore lower gaseous concentrations than PCDD/Fs. Compared to the existing global data of airborne PCDD/Fs and PBDD/Fs, our data of the MSWI vicinity were at medium levels, despite PAS samples only represent the concentrations of gaseous dioxins in theory. The seasonal data suggest that meteorological conditions exerted apparent influences over the concentrations and sources of airborne dioxins around the MSWI. As for PCDD/Fs, the MSWI was diagnosed as their uppermost source, followed by local traffic and volatilization/deposition. Whereas the top three PBDD/F sources were related to PBDEs, bromophenol/bromobenzene, and traffic vehicles, respectively. The bioassay-derived TEQs based on the aryl hydrocarbon receptor activation of airborne dioxins around the MSWI were one or two orders of magnitudes higher than their concentration-based TEQs, and the corresponding carcinogenic risks at some MSWI-vicinal sites exceeded the acceptable threshold proposed by the U. S. EPA (10−6 ∼ 10−4) and deserve continuous attention.

AIM:To investigate the factors affecting patients with post traumatic infectious endophthalmitis(PTIE)relieving from blindness.METHODS: A retrospective study was conducted on 169 patients(169 eyes)with PTIE from January 2010 to December 2020 in the department of ophthalmology, the Affiliated Hospital of Nantong University. After treatment of intravitreal injection of antibiotics(IVIA)and/or pars plana vitrectomy(PPV), the patients were divided into the getting rid of blindness group(103 eyes)and unilateral blindness group(66 eyes)according to the last follow-up of best correct visual acuity(BCVA)≥0.05. The factors affecting the patients to get rid of blindness were analyzed.RESULTS: The rate of relieving from blindness was 53.5%. Univariate analysis showed that BCVA before treatment ≥ hand movement, no retinal detachment, fundus grade of endophthalmitis < grade 3 and no strong virulence of infected microorganisms were beneficial for patients to get rid of blindness(P

Abstract We investigated for the first time the proteomic profiles both in the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) of major depressive disorder (MDD) and bipolar disorder (BD) patients. Cryostat sections of DLPFC and ACC of MDD and BD patients with their respective well-matched controls were used for study. Proteins were quantified by tandem mass tag and high-performance liquid chromatography-mass spectrometry system. Gene Ontology terms and functional cluster alteration were analyzed through bioinformatic analysis. Over 3000 proteins were accurately quantified, with more than 100 protein expressions identified as significantly changed in these two brain areas of MDD and BD patients as compared to their respective controls. These include OGDH, SDHA and COX5B in the DLPFC in MDD patients; PFN1, HSP90AA1 and PDCD6IP in the ACC of MDD patients; DBN1, DBNL and MYH9 in the DLPFC in BD patients. Impressively, depending on brain area and distinct diseases, the most notable change we found in the DLPFC of MDD was ‘suppressed energy metabolism’; in the ACC of MDD it was ‘suppressed tissue remodeling and suppressed immune response’; and in the DLPFC of BD it was differentiated ‘suppressed tissue remodeling and suppressed neuronal projection’. In summary, there are distinct proteomic changes in different brain areas of the same mood disorder, and in the same brain area between MDD and BD patients, which strengthens the distinct pathogeneses and thus treatment targets.

Abstract Recently, borophene has attracted extensive interest as the wonder material, showing that line defects (LDs) occur widely at the interface between $$\nu _{1/5}$$ ν 1 / 5 and $$\nu _{1/6}$$ ν 1 / 6 boron sheets. Here, we study theoretically the electron transport through two-terminal disordered borophene nanoribbons (BNRs) with random distribution of LDs. Our results indicate that LDs strongly affect the electron transport properties of BNRs. Both $$\nu _{1/5}$$ ν 1 / 5 and $$\nu _{1/6}$$ ν 1 / 6 BNRs exhibit metallic behavior without any LD, in agreement with experiments. While in the presence of LDs, the overall electron transport ability is dramatically decreased, but some resonant peaks of conductance quantum are found in the transmission spectrum of any disordered BNR with arbitrary arrangement of LDs. These disordered BNRs exhibit metal-insulator transition with tunable transmission gap in the insulating regime. Furthermore, two evolution phenomena of resonant peaks are revealed for disordered BNRs with different widths. These results may help for understanding structure-property relationships and designing LD-based nanodevices.

Four new species of the genus Metachelifer Redikorzev, 1938 are described from caves in the provinces of Tak (M. takensis sp. nov. and M. thailandicus sp. nov.), Chiangmai (M. mahnerti sp. nov.), and Nakhon Ratchasima (M. cheni sp. nov.). An identification key is provided to all known world representatives of the genus Metachelifer.

BackgroundRuptured abdominal aortic aneurysms (rAAAs) are challenging for vascular surgeons because they have a high mortality rate. In many diseases, nutritional status is closely associated with prognosis. The Controlling Nutritional Status (CONUT) screening tool score is a prognostic factor in some malignant and chronic diseases; however, the impact of nutritional status on rAAA has not yet been reported. In this study, we explored the relationship between the CONUT score and the postoperative prognosis of patients with rAAA.MethodsThis was a retrospective review of 39 patients with rAAA who underwent surgical treatment from March 2018 to September 2021 at one center. Patient characteristics, nutritional status (CONUT score), and postoperative status were recorded. The patients were divided into groups A and B based on the CONUT score. The baseline characteristics of the two groups were compared, and Cox proportional hazards and logistic regression analyses were used to determine independent predictors of mid-term mortality and complications, respectively.ResultsThe overall mid-term mortality rate was 28.21% (11/39). Compared with group A, group B had higher intraoperative (P = 0.047) and mid-term mortality (P = 0.033) rates. The univariate analysis showed that age [hazard ratio (HR), 1.098; 95% confidence interval (CI), 1.019–1.182; P = 0.014], CONUT score (HR, 1.316; 95% CI, 1.027–1.686; P = 0.03), and surgical procedure (HR, 0.127; 95% CI, 0.016–0.992; P = 0.049) were associated with mid-term mortality, whereas the multivariate analysis showed that the CONUT score (HR, 1.313; 95% CI, 1.009–1.710; P = 0.043) was an independent predictor of mid-term mortality. The multivariate logistic regression analysis did not reveal any associations with complications. The Kaplan–Meier curves showed that group B had a lower mid-term survival rate (log-rank P = 0.024).ConclusionMalnutrition is closely associated with the prognosis of patients with rAAA, and the CONUT score can be used to predict mid-term mortality.

IntroductionEpidemiological studies show that women have a higher prevalence of Alzheimer’s disease (AD) than men. Peripheral estrogen reduction during aging in women is proposed to play a key role in this sex-associated prevalence, however, the underlying mechanism remains elusive. We previously found that transcription factor early growth response-1 (EGR1) significantly regulates cholinergic function. EGR1 stimulates acetylcholinesterase (AChE) gene expression and is involved in AD pathogenesis. We aimed to investigate whether the triple-transgenic AD (3xTg-AD) mice harboring PS1M146V, APPSwe, and TauP301L show sex differences in β-amyloid (Aβ) and hyperphosphorylated tau (p-Tau), the two primary AD hallmarks, and how local 17β-estradiol (E2) may regulate the expression of EGR1 and AChE.MethodsWe first sacrificed male and female 3xTg-AD mice at 3–4, 7–8, and 11–12 months and measured the levels of Aβ, p-Tau, EGR1, and AChE in the hippocampal complex. Second, we infected SH-SY5Y cells with lentivirus containing the amyloid precursor protein construct C99, cultured with or without E2 administration we measured the levels of extracellular Aβ and intracellular EGR1 and AChE.ResultsFemale 3xTg-AD mice had higher levels of Aβ compared to males, while no p-Tau was found in either group. In SH-SY5Y cells infected with lentivirus containing the amyloid precursor protein construct C99, we observed significantly increased extracellular Aβ and decreased expression of intracellular EGR1 and AChE. By adding E2 to the culture medium, extracellular Aβ(1–42) was significantly decreased while intracellular EGR1 and AChE expression were elevated.DiscussionThis data shows that the 3xTg-AD mouse model can be useful for studying the human sex differences of AD, but only in regards to Aβ. Furthermore, in vitro data shows local E2 may be protective for EGR1 and cholinergic functions in AD while suppressing soluble Aβ(1–42) levels. Altogether, this study provides further in vivo and in vitro data supporting the human epidemiological data indicating a higher prevalence of AD in women is related to changes in brain estrogen levels.

High-oleic acid peanut oil (HOPO) and extra-virgin olive oil (EVOO) have been reported previously to have an attenuating effect on metabolic syndrome (MS). This study aimed to evaluate the metabolic effect of HOPO and EVOO supplementation in attenuating MS and the role of gut microbiota in regulating the metabolic profile. Sprague-Dawley rats were continuously fed with a normal diet, high-fructose and high-fat (HFHF) diet, HFHF diet containing HOPO, or a HFHF diet containing EVOO for 12 weeks. The metabolomics profiles of feces and serum samples were compared using untargeted metabolomics based on UPLC-Q/TOF-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to identify the potential fecal and serum biomarkers from different groups. Correlation between gut microbiota and biomarkers was assessed, and pathway analysis of serum biomarkers was conducted. Differences in metabolic patterns in feces and serum were observed among different groups. There were 8 and 12 potential biomarkers in feces and 15 and 6 potential biomarkers in serum of HOPO group and EVOO group, respectively, suggesting that HOPO and EVOO supplementation mainly altered amino acids, peptides, and their analogs in feces and serum. The branched-chain amino acids (BCAAs) biosynthesis pathway was identified as a major pathway regulated by HOPO or EVOO. This study suggests that HOPO and EVOO supplementation ameliorate diet-induced MS, mainly via modulation of the BCAAs biosynthesis pathway.

Abstract Elevated lipoprotein(a) [Lp(a)] is a risk factor for coronary heart disease (CHD), but there are few studies on the prediction of future cardiovascular events by Lp(a) and its LPA single nucleotide polymorphisms (SNPs). The aim of this study was to investigate whether elevated Lp(a) and its SNPs can predict cardiovascular events. We evaluated whether Lp(a) and LPA SNPs rs6415084 and rs12194138 were associated with the incidence rate and severity of CHD. All participants were followed up for 5 years. Elevated Lp(a) is an independent risk factor for the risk and severity of CHD (CHD group vs. control group: OR = 1.793, 95% CI: 1.053–2.882, p = 0.043; multiple-vessel disease group vs. single-vessel disease group: OR = 1.941, 95% CI: 1.113–3.242, p = 0.027; high GS group vs. low GS group: OR = 2.641, 95% CI: 1.102–7.436, p = 0.040). Both LPA SNPs were risk factors for CHD, and were positively associated with the severity of CHD (LPA SNPs rs6415084: CHD group vs. control group: OR = 1.577, 95% CI: 1.105–1.989, p = 0.004; multiple-vessel disease group vs. single-vessel disease group: OR = 1.613, 95% CI: 1.076–2.641, p = 0.030; high GS group vs. low GS group: OR = 1.580, 95% CI: 1.088–2.429, p = 0.024; LPA SNPs rs12194138: CHD group vs. control group: OR = 1.475, 95% CI: 1.040–3.002, p = 0.035; multiple-vessel disease group vs. single-vessel disease group: OR = 2.274, 95% CI: 1.060–5.148, p = 0.038; high GS group vs. low GS group: OR = 2.067, 95% CI: 1.101–4.647, p = 0.021). After 5 years of follow-up, elevated Lp(a) and LPA SNPs rs6415084 and rs12194138 can independently predict cardiovascular events. The increase of serum Lp(a) and LPA SNPs rs6415084 and rs12194138 are associated with increased prevalence and severity of CHD, and can independently predict cardiovascular events.

Abstract As a distributed storage scheme, the blockchain network lacks storage space has been a long-term concern in this field. At present, there are relatively few research on algorithms and protocols to reduce the storage requirement of blockchain, and the existing research has limitations such as sacrificing fault tolerance performance and raising time cost, which need to be further improved. Facing the above problems, this paper proposes a protocol based on Distributed Image Storage Protocol (DISP), which can effectively improve blockchain storage space and reduces computational costs in the help of InterPlanetary File System (IPFS). In order to prove the feasibility of the protocol, we make full use of IPFS and distributed database to design a simulation experiment for blockchain. Through distributed pooling (DP) algorithm in this protocol, we can divide image evidence into recognizable several small files and stored in several nodes. And these files can be restored to lossless original documents again by inverse distributed pooling (IDP) algorithm after authorization. These advantages in performance create conditions for large scale industrial and commercial applications.

Abstract Objectives Kashgar prefecture is an important transportation and trade hub with a high incidence of tuberculosis. The following study analyzed the composition and differences in Mycobacterium tuberculosis (M.tb) lineage and specific tags to distinguish the lineage of the M.tb in Kashgar prefecture, thus providing a basis for the classification and diagnosis of tuberculosis in this area. Methods Whole-genome sequencing (WGS) of 161 M.tb clinical strains was performed. The phylogenetic tree was constructed using Maximum Likelihood (ML) based on single nucleotide polymorphisms (SNPs) and verified through principal component analysis (PCA). The composition structure of M.tb in different regions was analyzed by combining geographic information. Results M.tb clinical strains were composed of lineage 2 (73/161, 45.34%), lineage 3 (52/161, 32.30%) and lineage 4 (36/161, 22.36%). Moreover, the 3 lineages were subdivided into 11 sublineages, among which lineage 2 included lineage 2.2.2/Asia Ancestral 1 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 2 (9/73, 12.33%), lineage 2.2.1-Asia Ancestral 3 (18/73, 24.66%), and lineage 2.2.1-Modern Beijing (39/73, 53.42%). Lineage 3 included lineage 3.2 (14/52, 26.92%) and lineage 3.3 (38/52, 73.08%), while lineage 4 included lineage 4.1 (3/36, 8.33%), lineage 4.2 (2/36, 5.66%), lineage 4.4.2 (1/36, 2.78%), lineage 4.5 (28/36, 77.78%) and lineage 4.8 (2/36, 5.66%), all of which were consistent with the PCA results. One hundred thirty-six markers were proposed for discriminating known circulating strains. Reconstruction of a phylogenetic tree using the 136 SNPs resulted in a tree with the same number of delineated clades. Based on geographical location analysis, the composition of Lineage 2 in Kashgar prefecture (45.34%) was lower compared to other regions in China (54.35%-90.27%), while the composition of Lineage 3 (32.30%) was much higher than in other regions of China (0.92%-2.01%), but lower compared to the bordering Pakistan (70.40%). Conclusion Three lineages were identified in M.tb clinical strains from Kashgar prefecture, with 136 branch-specific SNP. Kashgar borders with countries that have a high incidence of tuberculosis, such as Pakistan and India, which results in a large difference between the M.tb lineage and sublineage distribution in this region and other provinces of China.

The purpose of this work was to reveal the effect of phosphating pre-treatment on the protective performance of water-based epoxy varnish coating on surface of aluminum alloy(AA).A phosphating film was firstly prepared on the surface of 2024 aluminum alloy by chemical conversion method for phosphating pre-treatment, and then the surface of aluminum alloy without and after phosphating pre-treatment was coated with water-based epoxy varnish.After the varnish was completely cured into a coating, the protective effect of water-based epoxy coating on aluminum alloy without and after phosphating pre-treatment was evaluated by electrochemical impedance spectroscopy(EIS).Finally, the effect of phosphating pre-treatment on the protective performance of water-based epoxy varnish coating and its mechanism were revealed.Results showed that the phosphating coating on surface of aluminum alloy had a uniform and dense columnar crystal structure, which was mainly composed of Zn3(PO4)2·4H2O.In 3.5%(mass fraction)NaCl solution, both the protective layer resistance(Rc)and the impedance module at low frequency(|Z|0.01)of the epoxy/AA(E/A)system and the epoxy/phosphating coating/AA(E/P/A)system decreased gradually with the extension of immersion time; however, both Rc and|Z|0.01 of the E/P/A system were always greater than those of the E/A system.On the other hand, due to the phosphating pre-treatment, the average adhesive force(Fa)of water-based epoxy coating on the surface of AA increased from 10.47 MPa to 15.58 MPa.Compared with the direct coating of water-based epoxy varnish without phosphating pretreatment on the surface of AA, the coating with phosphating pre-treatment before water-based epoxy varnish treatment changed the whole protective layer on the surface of AA from a single epoxy layer to a composite epoxy layer/phosphating coating, resulting in a significant increase in Rc and|Z|0.01.More importantly, the existence of phosphating film improved the adhesion of water-based epoxy coating on the surface of AA, and even fundamentally changed the fracture form of the whole protective layer.The combined effects of the above two aspects improved the protective effect of water-based epoxy varnish coating on AA substrate.Also, the mechanism of phosphating pre-treatment on improving the protective performance of water-based epoxy varnish coating was revealed.

Abstract Root zone microbial structure is particularly complex in plants with rhizosheaths, and greater understanding of the rhizosheath may play an important role in the future development of sustainable agricultural practices. However, one important reason to focus study on rhizosheath microbial structure is that there is no definite method for rhizosheath separation. The aim of this study was to explore rhizosheath isolation methods and the diversity characteristics of microorganisms around the rhizosphere. In this study, we isolated the rhizosheath of Stipa grandis, a dominant species in desert steppe, and the microorganisms in the roots, root epidermis, rhizosheath and rhizosphere soil were extracted and sequenced by 16S rRNA and ITS. The alpha diversity index of bacteria in Stipa grandis rhizosphere soil was the greatest, followed by rhizosheath, and the alpha diversity index of endophytic bacteria in root system was the smallest. The alpha diversity index of fungi in the rhizosheath and rhizosphere soil were significantly higher than that in the root epidermis and root system. There were significant differences in bacterial community structure between the root epidermis, endophytic bacteria, rhizosheath and rhizosphere soil. Unlike bacterial community structure, the community structure of fungi in the root epidermis was similar that of endophytic fungi, but significantly different from those in rhizosheath and rhizosphere soil. This study demonstrated a feasible method for separating plant rhizosheath and root epidermis. We suggest that the root epidermis can act as the interface between the host plant root and the external soil environment. We will have to re-examine the biological and ecological significance of rhizosheath and microorganisms in rhizosheath, as well as the mechanism explaining the close relationship of the rhizosheath and the plant root epidermis. This study provides theoretical and technical guidance for the isolation of the plant rhizosheath and the study of microorganisms in plant rhizosheath.

Background: Cancer-induced Bone Pain (CIBP) is an important factor affecting their quality of life of cancer survivors. In addition, current clinical practice and scientific research suggest that neuropathic pain is a representative component of CIBP. However, given the variability of cancer conditions and the complexity of neuropathic pain, related mechanisms have been continuously supplemented but have not been perfected. Aim of Review: Therefore, the current review highlights the latest progress in basic research on the field and proposes potential therapeutic targets, representative drugs and upcoming therapies. Key Scientific Concepts of Review: Notably, factors such as central sensitization, neuroinflammation, glial cell activation and an acidic environment are considered to be related to neuropathic pain in CIBP. Nonetheless, further research is needed to ascertain the mechanism of CIBP in order to develop highly effective drugs. Moreover, more attention needs to be paid to the care of patients with advanced cancer.

Blockchain is one of the technical hotspots in recent years,and the research theories related to it are being enriched.However,it is still facing the key problem of small throughput and low processing efficiency before it can be implemented into the industry.In response to this problem,cross-chain technology has been widely focused as a blockchain technology that has the potential to both expand throughput processing capacity and improve processing efficiency.This paper presents a novel hash-time-lock-contract based cross-chain token swap mechanism (NCASP),which creatively introduces an account system for the Fabric blockchain and integrates smart contract technology to achieve secure and seamless asset exchange between the Ethernet and Fabric blockchain network.The NCASP protocol sets up different intermediate accounts for asset escrow and transfer in each HTLC transfer,and destroys them in time after the transaction is completed,making the original cross-chain transaction rate unchanged while ensuring the security of the transaction.Simulation of the protocol shows that the protocol is applicable to the federated chain represented by Fabric and the public chains represented by Bitcoin and Ethernet,can achieve efficient and secure cross-chain asset exchange without the intervention of third-party blockchains,and can save about 26.8% in transaction efficiency compared with the cross-chain scheme of BSN (blockchain service network).The improved protocol extends the usage scenarios of the traditional HTLC cross-chain asset schemes,enabling the exchange of assets between different users with a balance of atomicity,fairness and transparency.

The empirical study proposes a model for investigating the effect of entrepreneurial leadership on job insecurity and employee psychological wellbeing during COVID-19 based on the combined theoretical grounds of The Conservation of Resources Theory and Social Learning. To explore the job insecurity relationship with psychological wellbeing, and measure the impact of Fear of COVID-19, an empirical study was conducted on a sample of 408 employees in Croatia. The data of the cross-sectional study was collected in November and December 2020. A strong influence of job insecurity on the psychological wellbeing of employees has been identified. Furthermore, fear of COVID-19 was found to have adverse psychological effects on wellbeing. The theorized positive impact of entrepreneurial leadership on job insecurity was not supported by the evidence. The strong point of our contribution lies in the finding that the entrepreneurial leadership style alone does not buffer against job insecurity, thus pointing that the more comprehensive inquiry into other organizational factors, such as coping, learning abilities, developmental opportunities, personal disposition, and pressure bearing. The research is the first step toward enhancing our understanding of the entrepreneurial dimension of transactional psychology. The observations we recorded have implications for research into the study of the mental processes and their impact on organizational proactive behavior.

Background and aimsThe disease burden attributable to metabolic risk factors is rapidly increasing in China, especially in older people. The objective of this study was to (i) estimate the pattern and trend of six metabolic risk factors and attributable causes in China from 1990 to 2019, (ii) ascertain its association with societal development, and (iii) compare the disease burden among the Group of 20 (G20) countries.MethodsThe main outcome measures were disability-adjusted life-years (DALYs) and mortality (deaths) attributable to high fasting plasma glucose (HFPG), high systolic blood pressure (HSBP), high low-density lipoprotein (HLDL) cholesterol, high body-mass index (HBMI), kidney dysfunction (KDF), and low bone mineral density (LBMD). The average annual percent change (AAPC) between 1990 and 2019 was analyzed using Joinpoint regression.ResultsFor all six metabolic risk factors, the rate of DALYs and death increased with age, accelerating for individuals older than 60 and 70 for DALYs and death, respectively. The AAPC value in rate of DALYs and death were higher in male patients than in female patients across 20 age groups. A double-peak pattern was observed for AAPC in the rate of DALYs and death, peaking at age 20–49 and at age 70–95 plus. The age-standardized rate of DALYs increased for HBMI and LBMD, decreased for HFPG, HSBP, KDF, and remained stable for HLDL from 1990 to 2019. In terms of age-standardized rate of DALYs, there was an increasing trend of neoplasms and neurological disorders attributable to HFPG; diabetes and kidney diseases, neurological disorders, sense organ diseases, musculoskeletal disorders, neoplasms, cardiovascular diseases, digestive diseases to HBMI; unintentional injuries to LBMD; and musculoskeletal disorders to KDF. Among 19 countries of Group 20, in 2019, the age-standardized rate of DALYs and death were ranked fourth to sixth for HFPG, HSBP, and HLDL, but ranked 10th to 15th for LBMD, KDF, and HBMI, despite the number of DALYs and death ranked first to second for six metabolic risk factors.ConclusionsPopulation aging continuously accelerates the metabolic risk factor driven disease burden in China. Comprehensive and tight control of metabolic risk factors before 20 and 70 may help to mitigate the increasing disease burden and achieve healthy aging, respectively.

Summary: Background: BNT162b2, an mRNA vaccine against COVID-19, is being utilised worldwide, but immunogenicity and safety data in Chinese individuals are limited. Methods: This phase 2, randomised, double-blind, placebo-controlled trial included healthy or medically stable individuals aged 18–85 years enrolled at two clinical sites in China. Participants were stratified by age (≤55 or >55 years) and randomly assigned (3:1) by an independent randomisation professional to receive two doses of intramuscular BNT162b2 30 μg or placebo, administered 21 days apart. Study participants, study personnel, investigators, statisticians, and the sponsor's study management team were blinded to treatment assignment. Primary immunogenicity endpoints were the geometric mean titers (GMTs) of neutralising antibodies to live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and seroconversion rates (SCR) 1 month after the second dose. Safety assessments included reactogenicity within 14 days of vaccination, adverse events (AEs), and clinical laboratory parameters. Randomised participants who received at least one dose were included in the efficacy and safety analyses on a complete case basis (incomplete/missing data not imputed). Results up to 6 months after the second dose are reported. Findings: Overall, 959 participants (all of Han ethnicity) who were recruited between December 5th, 2020 and January 9th, 2021 received at least one injection (BNT162b2, n=720; placebo, n=239). At 1 month after the second dose, the 50% neutralising antibody GMT was 294.4 (95% CI; 281.1–308.4) in the BNT162b2 group and 5.0 (95% CI; 5.0–5.0) in the placebo group. SCRs were 99.7% (95% CI; 99.0%–100.0%) and 0% (95% CI; 0.0%–1.5%), respectively (p

Threshold signatures are fundamental tools for multi-party information security protocols.It is widely used in fields such as identity authentication,anti-counterfeiting and tamper-resistance.We introduce a new decentralized threshold signature protocol BHTSP which combines distributed key generation (DKG) and BLS signature.The protocol allows multi-party participation and generates a signature of constant size.We implement this protocol with smart contract as the communication layer for secure parameter exchange.Experimental simulation results show that BHTSP can generate threshold signature with constant size.It reduced the memory consumption for aggregated public key combinations needed in signature verification by 85.3% compared to Schnorr signature.In the experimental blockchain platform,BHTSP is able to support the generation of threshold signatures involving up to 50 participants,optimizing the execution process for blockchain multi-party transactions.

AIM: To explore the correlation between cystatin C (Cys-C) and diabetic retinopathy (DR) in those patients with type 2 diabetes mellitus (DM) in China. METHODS: Articles were collected from China National Knowledge Infrastructure (CNKI), Wanfang, VIP, PubMed, EMBASE, Cochrane Library, Clinical Trials.gov, and Google Scholar. Quality and risk of bias within included studies was assessed using the Newcastle-Ottawa scale (NOS). Heterogeneity was determined by using Cochran's Q-test and Higgins I2 statistics. Mean differences (MDs) and 95% confidence intervals (CIs) of Cys-C within the diabetes without retinopathy (DWR) and DR, DWR and non-proliferative diabetic retinopathy (NPDR), NPDR and proliferative diabetic retinopathy (PDR) were collected by using random-effects model because of high heterogeneity. Meta-analysis was conducted based on 23 articles of 2331 DR including NPDR and PDR patients and 2023 DWR patients through Review Manager 5.3. Subgroup analyses were also performed according to DM duration, body mass index (BMI), total cholesterol (TC), total triglycerides (TG), low-density lipoprotein C (LDL-C), and high-density lipoprotein C (HDL-C), sample origins and methods. Publication bias was assessed by the funnel plot. RESULTS: Cys-C level in DR patients was increased compared with that of DWR (total MD: 0.69, 95%CI: 0.41 to 0.97, Z=4.79, P