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Abstract The major polluting aspects of our global fashion industries are the textile wastewater that turns black all our freshwater reservoirs. Nano-filtration through membrane technology is one of the biggest solutions of industrial wastewater treatment but the fouling of membrane is the major limitation of previous work. In this research, novel PVDF/MoS2-TNT (PMT) nanocomposite membranes were fabricated through a modified In-situ polymerisation phase inversion method. X-ray diffraction (XRD) analysis also confirmed the β-phase of PVDF within the developed PVDF/MoS2-TNT membrane. XPS analysis provides evidence about the presence of a specific chemical states of titanium nanotube and molybdenum disulphide which is involved in the photocatalytic degradation of pollutant molecules. Scanning electron microscope (SEM) shows that our membranes are porous in nature. PVDF/MoS2-TNT membranes exhibit excellent filtration efficiency (∼97%) for textile wastewater. The results and outcomes of the research demonstrate that PMT membranes have enormous potential in the commercial application of textile wastewater treatment.

Abstract Crizotinib carries an FDA hepatotoxicity warning, yet analysis of the FAERS database suggests that the severity of its hepatotoxicity risks, including progression to hepatitis and liver failure, might be underreported. However, the underlying mechanism remains poorly understood, and effective intervention strategies are lacking. Here, mRNA-sequencing analysis, along with KEGG and GO analyses, revealed that DEGs linked to Crizotinib-induced hepatotoxicity predominantly associate with the ferroptosis pathway which was identified as the principal mechanism behind Crizotinib-induced hepatocyte death. Furthermore, we found that ferroptosis inhibitors, namely Ferrostatin-1 and Deferoxamine mesylate, significantly reduced Crizotinib-induced hepatotoxicity and ferroptosis in both in vivo and in vitro settings. We have also discovered that overexpression of AAV8-mediated Nrf2 could mitigate Crizotinib-induced hepatotoxicity and ferroptosis in vivo by restoring the imbalance in glutathione metabolism, iron homeostasis, and lipid peroxidation. Additionally, both Stat1 deficiency and the Stat1 inhibitor NSC118218 were found to reduce Crizotinib-induced ferroptosis. Mechanistically, Crizotinib induces the phosphorylation of Stat1 at Ser727 but not Tyr701, promoting the transcriptional inhibition of Nrf2 expression after its entry into the nucleus to promote ferroptosis. Meanwhile, we found that MgIG and GA protected against hepatotoxicity to counteract ferroptosis without affecting or compromising the anti-cancer activity of Crizotinib, with a mechanism potentially related to the Stat1/Nrf2 pathway. Overall, our findings identify that the phosphorylation activation of Stat1 Ser727, rather than Tyr701, promotes ferroptosis through transcriptional inhibition of Nrf2, and highlight MgIG and GA as potential therapeutic approaches to enhance the safety of Crizotinib-based cancer therapy.

Abstract Background Breast cancer (BC), a common malignant tumor originating from the terminal ductal lobular unit of the breast, poses a substantial health risk to women. Previous studies have associated cytochrome b561 (CYB561) with a poor prognosis in BC; however, its underlying mechanism of this association remains unclear. Methods We investigated the expression of CYB561 mRNA in BC using databases such as The Cancer Genome Atlas, Gene Expression Omnibus, Tumor–Normal–Metastatic plot, and Kaplan–Meier plotter databases. The prognostic value of CYB561 protein in BC was assessed in relation to its expression levels in tumor tissue samples from 158 patients with BC. The effect of CYB561 on BC progression was confirmed using in vivo and in vitro experiments. The biological functions and related signaling pathways of CYB561 in BC were explored using gene microarray, Innovative Pathway, Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. The correlation between CYB561 and the BC tumor immune microenvironment was evaluated using the CIBERSORT algorithm and single-cell analysis and further validated through immunohistochemistry of serial sections. Results Our study demonstrated that upregulation of CYB561 expression predicted poor prognosis in patients with BC and that CYB561 knockdown inhibited the proliferation, migration, and invasive ability of BC cells in vitro. CYB561 knockdown inhibited BC tumor formation in vivo.CYB561 was observed to modulate downstream tropomyosin 1 expression. Furthermore, CYB561 expression was associated with macrophage M2 polarization in the BC immune microenvironment. Conclusions Elevated CYB561 expression suggests a poor prognosis for patients with BC and is associated with macrophage M2 polarization in the BC microenvironment. Therefore, CYB561 could potentially serve as a therapeutic target for BC treatment.

Abstract Cell adhesion to the extracellular matrix and its natural outcome of cell spreading, along with the maintenance of barrier activity, are essential behaviors of epithelial cells, including retinal pigment epithelium (RPE). Disruptions in these characteristics can result in severe vision-threatening diseases such as diabetic macular edema and age-related macular degeneration. However, the precise mechanisms underlying how RPE cells regulate their barrier integrity and cell spreading are not fully understood. This study aims to elucidate the relative importance of upper glycolytic components in governing these cellular behaviors of RPE cells. Electric Cell-Substrate Impedance Sensing (ECIS) technology was utilized to assess in real-time the effects of targeting various upper glycolytic enzymes on RPE barrier function and cell spreading by measuring cell resistance and capacitance, respectively. Specific inhibitors used included WZB117 for Glut1 inhibition, Lonidamine for Hexokinase inhibition, PFK158 for PFKFB3/PFK axis inhibition, and TDZD-8 for Aldolase inhibition. Additionally, the viability of RPE cells was evaluated using a lactate dehydrogenase (LDH) cytotoxicity assay. The most significant decrease in electrical resistance and increase in capacitance of RPE cells were observed due to dose-dependent inhibition of Glut1 using WZB117, as well as Aldolase inhibition with TDZD-8. LDH level analysis at 24–72 h post-treatment with WZB117 (1 and 10 μM) or TDZD-8 (1 μM) showed no significant difference compared to the control, indicating that the disruption of RPE functionality was not attributed to cell death. Lastly, inhibition of other upper glycolytic components, including PFKFB3/PFK with PFK158 or Hexokinase with Lonidamine, did not significantly affect RPE cell behavior. This study provides insights into the varied roles of upper glycolytic components in regulating the functionality of RPE cells. Specifically, it highlights the critical roles of Glut1 and Aldolase in preserving barrier integrity and promoting RPE cell adhesion and spreading. Such understanding will guide the development of safe interventions to treat RPE cell dysfunction in various retinal disorders.

Objective To analyze the mechanism that Hcp1 protein in type Ⅵ secretion system of Burkholderia pseudomallei (B. pseudomallei) mediates the formation of multinucleated giant cells (MNGCs) when host cells are infected by the bacterium. Methods The mutant strain (BPC006 Δhcp1) and complementation strain (BPC006 Δhcp1:: hcp1) were constructed by homologous recombination and plasmid complement technology, respectively. After RAW264.7 cells were infected with B. pseudomallei, the localization of Hcp1 in host cells was analyzed by immunofluorescence staining. The localization was further verified by cytoplasmic-membrane isolation in 293T cells after transfecting pCDNA4.1-Hcp1. The biological significance and effect of Hcp1 were explored by the anti-Hcp1 polyclonal antibody blocking and the formation of MNGC was detected by Giemsa staining. Results Western blotting showed that BPC006 Δhcp1 could not express Hcp1, while BPC006 Δhcp1:: hcp1 restored Hcp1 expression. The above results proved that the mutant and complement strains were successfully constructed. Both cellular immunofluorescence co-localization and cytoplasmic-membrane isolation experiments showed that Hcp1 localized to host cell membranes. Last but not least, compared with the control group, anti-Hcp1 polyclonal antibodies inhibited the formation of MNGC (P < 0.01). Conclusion Hcp1 protein in type Ⅵ secretion system of B. pseudomallei is able to translocate to the RAW264.7 cell membranes and plays an important role in the formation of MNGCs.

Fully bioresorbable vascular scaffolds (BVSs) aim to overcome the limitations of metallic drug-eluting stents (DESs). However, polymer-based BVSs, such as Abbott's Absorb, the only US FDA-approved BVS, have had limited use due to increased strut thickness (157 μm for Absorb), exacerbated tissue inflammation, and increased risk of major cardiac events leading to inferior clinical performance when compared to metallic DESs. Herein we report the development of a drug-eluting BVS (DE-BVS) through the innovative use of a photopolymerizable, citrate-based biomaterial and a high-precision additive manufacturing process. BVS with a clinically relevant strut thickness of 62 μm can be produced in a high-throughput manner, i.e. one BVS per minute, and controlled release of the anti-restenosis drug everolimus can be achieved by engineering the structure of polymer coatings to fabricate drug-eluting BVS. We achieved the successful deployment of BVSs and DE-BVSs in swine coronary arteries using a custom-built balloon catheter and BVS delivery system and confirmed BVS safety and efficacy regarding maintenance of vessel patency for 28 days, observing an inflammation profile for BVS and DE-BVS that was comparable to the commercial XIENCE™ DES (Abbott Vascular).

High-order wave mixing in solid-state platforms gather increasing importance due to the development of advanced lasers and integrated photonic circuit for both classical and quantum information. However, the high-order wave mixing is generally inefficient in solids under weak pump. Here, we observed the presence of phase matching of five-wave mixing (5WM) propagating in a zinc oxide (ZnO) microwire. The 5WM signal is enhanced by 2–3 orders of magnitude under the phase matching conditions, reaching an absolute conversion efficiency of 1.7 × 10−13 when the peak pumping power density is about 106 W/cm2. The propagation of multiple nonlinear signals, including sum frequency generation, third harmonic generation, four-wave mixing etc., benefited from both the large nonlinear coefficients and the wide transparent window of ZnO, implies the possibility of developing cascaded nonlinear process under higher pumping. This study enriches the ZnO platform for integrated nonlinear nanophotonics.

Objective To investigate the key physical and chemical properties of nintedanib liposomes prepared by 4 different methods in order to screen out the best preparation method of nintedanib liposomes. Methods Firstly, nintedanib liposomes were prepared by thin film dispersion, reverse evaporation, ethanol injection and modified ethanol injection, respectively. The entrapment efficiency of nintedanib liposomes was then determined by dialysis and characterized for particle size, dispersibility, surface potential, and morphology. Their stability was evaluated after being placed at room temperature for 7 d. Results Circular nintedanib liposomes were respectively prepared by thin film dispersion, reverse evaporation, ethanol injection and modified ethanol injection, with a particle size of (285.1±12.3), (271.4±5.9), (226.3±14.8) and (197.2±11.2) nm, an encapsulation rate of (15.82±1.26)%, (16.71±1.35)%, (25.12±3.21)% and (32.5±3.61)%, respectively. The nintedanib liposomes prepared by modified ethanol injection had significantly smallest particle size and highest encapsulation efficiency than the liposomes by the other 3 methods (P < 0.05). In 7 d after being placed at room temperature, the particle sizes of the liposomes prepared by film dispersion and reverse evaporation were increased notably (P < 0.01), but no such change was observed in the liposomes prepared by ethanol injection and modified ethanol injection (P>0.05). Conclusion Nintedanib liposomes prepared by modified ethanol injection have excellent key physical and chemical properties, and this method is an optical one for preparing nintedanib liposomes.

Abstract Euglena gracilis (E. gracilis), pivotal in the study of photosynthesis, endosymbiosis, and chloroplast development, is also an industrial microalga for paramylon production. Despite its importance, E. gracilis genome exploration faces challenges due to its intricate nature. In this study, we achieved a chromosome-level de novo assembly (2.37 Gb) using Illumina, PacBio, Bionano, and Hi-C data. The assembly exhibited a contig N50 of 619 Kb and scaffold N50 of 1.12 Mb, indicating superior continuity. Approximately 99.83% of the genome was anchored to 46 chromosomes, revealing structural insights. Repetitive elements constituted 58.84% of the sequences. Functional annotations were assigned to 39,362 proteins, enhancing interpretative power. BUSCO analysis confirmed assembly completeness at 80.39%. This first high-quality E. gracilis genome offers insights for genetics and genomics studies, overcoming previous limitations. The impact extends to academic and industrial research, providing a foundational resource.

Since the 1990s, border security has been a pressing issue in political geography. With the increasing interactions between China and its neighboring countries, border security has increased the attention of scholars and government officials. Security issues along the China-Myanmar border are particularly eye-catching owing to Myanmar's fast-changing social and political reforms and unrest, as well as the complicated situation in Northern Myanmar that has gathered a large number of armed ethnic minorities. Tensions have resulted in prominent traditional and non-traditional security issues along the China-Myanmar border. Illegal cross-border trade is one non-traditional security problem in the region; specifically, illegal cross-border cattle trade is a particular but understudied case. This study investigates the actors, transportation, and social networks involved in illegal cross-border cattle trade. Using first-hand materials collected in the border area and secondary archives, the study analyzes the spatial and temporal features and operation mechanisms of smuggling. The main conclusions are as follows: (1) From the perspective of the time stage, the study identifies approximately three stages. Before 2004, the illegal cross-border cattle trade, relying on kin relationships, was in its embryonic stage. From 2004 to 2018, the domestic beef market was in short supply, and the illegal cross-border cattle trade, this time relying on nepotism, gradually became more frequent, reaching 1.6-2 million heads per year and entering the development stage. Since the outbreak of COVID-19 in 2018 and 2020, owing to the enhanced border control, the volume of illegal cross-border trade has plummeted, decreasing by around tens of thousands to more than 100,000 each year, and then entering a period of extinction. (2) Spatially, illegal cross-border trade mainly comprises three routes: the northern, central, and southern routes, from northern India to China's Yunnan Province through northern Myanmar. Among the three routes, the middle route sees the largest number of cross-border cattle, among which, the cross-border flow of cattle from Myanmar through the Yunnan Ruili Nongdao channel is the largest, followed by the northern route; the southern route sees the lowest number. (3) The China-Myanmar illegal cross-border cattle trade relies on the trust bond, regulation, and enforcement mechanism provided by the natural geographical environment and cross-border nepotism, thus forming a complete social network trade chain. The study suggests methods to control illegal cross-border trade by simplifying formal trade and strengthening the construction of smart borders. The findings provide reference for the prevention and control of illegal cross-border trade. Although illegal cross-border cattle trade can be regarded as a type of illegal cross-border trade, owing to the large volume of live cattle, the transportation is more difficult, and it is easier to detect. As such, the choice of illegal cross-border routes is quite different from that of general small goods and is more obviously affected by natural geographical conditions and social and interpersonal network factors. Thus, illegal cross-border cattle trade provides a unique case study of the relations between illegal cross-border trade and human, physical, and geographical conditions.

Abstract In this paper, a novel negative refractive index metamaterial (NIM) is developed and characterized. The proposed metamaterial exhibits negative effective permittivity (ε effe ) and negative effective permeability (µ effe ) at millimeter wave frequency of 28 GHz. This attractive feature is utilized to enhance the gain of a microstrip patch antenna (MPA). Two thin layers of 5 × 5 subwavelength unit cell array of NIM are placed above a single MPA to enhance the gain of the antenna. Each unit cell has an area of 3.4 × 3.4 mm2. A gain increase of 7.9 dBi has been observed when using the proposed NIM as a superstrate. Furthermore, the NIM array is placed over a 2 × 2 array of MPAs with four ports to demonstrate versatility of the metamaterial. The total size of the 2 × 2 antenna array system with N-MTM is about 61.1 × 34 × 16mm3 (5.71λ × 3.18λ × 1.5λ, where λ is the free-space wavelength at 28 GHz). The measurement result indicate that the maximum gain of the antenna array is 13.5dBi. A gain enhancement of 7.55 dB in E-Plane and 7.25 dB in H-Plane at the resonant frequency of 28 GHz is obtained. The proposed antenna structure is suitable for 5G millimeter wave communications, in particular, for possible implementation in future millimeter wave access points and cellular base stations.

Emmanuel Perrodin-Njoku,1 Sowmya R Rao,2 Regina M Wang,3 Christopher J Moreland,4 Poorna Kushalnagar1 1Center for Deaf Health Equity, Gallaudet University, Washington, DC, USA; 2Department of Global Health, Boston University School of Public Health, Boston, MA, USA; 3Family Medicine and Public Health, University of California San Diego, San Diego, CA, USA; 4Dell Medical School, University of Texas at Austin, Austin, TX, USACorrespondence: Poorna Kushalnagar, Gallaudet University, 800 Florida Avenue NE, Hall Memorial Building, Washington, DC, 20002, USA, Email poorna.kushalnagar@gallaudet.eduPurpose: Some deaf and hard-of-hearing (DHH) individuals face health information barriers, increasing their risk of diabetes mellitus (DM) and subsequent cancer development. This study examines if health-related quality of life (HRQoL) and deaf patient-reported outcomes (DHH-QoL) mediate the relationship between DM diagnosis and cancer screening adherence among DHH individuals.Patients and Methods: In a cross-sectional study, US DHH adults assigned female at birth answered questions on cervical and breast cancer screenings from the ASL-English bilingual Health Information National Trends Survey (HINTS-ASL) and the PROMIS (Patient Reported Outcome Measurement Information System) Deaf Profile measure’s Communication Health and Global Health domains. Odds ratios (OR) and 95% confidence intervals (CI) were obtained from multivariable logistic and linear regression models, examining the association between DM, DHH-QoL, and cancer screening adherence, adjusting for other covariates and HRQoL. A Baron and Kenny causal mediation analysis was used. A two-sided p < 0.05 indicated significance.Results: Most respondents were White (66.4%), heterosexual (66.2%), did not have DM (83.9%), had health insurance (95.5%), and adhered to pap smears (75.7%) and mammograms (76.9%). The average (standard deviation) DHH-QoL score was 50.9 (8.6). Those with DM had lower HRQoL scores (46.2 (9.5) vs 50.2 (8.8); p < 0.0001) than those without. Non-significant multivariable models indicate that those with DM were more adherent to pap testing (OR: 1.48; 95% CI: 0.72, 3.03; p = 0.285) and mammograms (2.18; 95% CI: 0.81, 5.88; p = 0.122), with DHH-QoL scores slightly increasing them to 1.53 (0.74, 3.16; p = 0.250) for pap testing and 2.55 (0.91, 7.13; p = 0.076) for mammograms. DHH-QoL was significantly associated with mammograms (p = 0.027), with 6% increased adherence per unit increase in the score. Overall, HRQoL and DHH-QoL were not significant mediators.Conclusion: While HRQoL/DHH-QoL in DHH individuals with DM does not mediate cancer screening adherence, higher DHH-QoL scores are associated with it. DHH-focused health literacy and communication training can improve cancer-related outcomes.Keywords: deaf, cancer screening, sign language, hearing loss, diabetes

Objective To investigate the law of surrounding soil displacement induced by construction under the arrangement of non-horizontal parallel double-line shield tunnels, a soil displacement calculation method based on modified Loganathan formula is proposed. Method The Loganathan formula and its relevant assumptions are introduced. Considering the comprehensive effects of ground loss, soil unloading rebound, and variation of soil loss rate along the excavation path caused by shield tunnel excavation disturbance, the Loganathan formula is modified, and a solution for soil displacement around a single-line shield tunnel is established. Then, a calculation method for soil displacement induced by construction in the case of non-horizontal parallel double-line shield tunnels is developed. The engineering applicability of the proposed method is validated through field monitoring and numerical simulation results of actual projects. Result & Conclusion The proposed calculation method can account for factors such as the angle (θ) between the tunnel axis line and the horizontal plane, the radius (R1,R2) of double-line tunnels, the spacing (D) between tunnel axes, and the buried depth (H1,H2) of double-line tunnels, and the influence of construction factors such as ground loss, soil unloading rebound, and variation of soil loss rate along the excavation path caused by shield tunnel construction disturbance on soil displacement. The average errors between theoretical calculation and field monitoring/numerical simulation results for land subsidence and horizontal soil displacement are 5.6% and 0.6%, and 5.5% and 5.3%, respectively. These errors all meet the 20% accuracy requirement specified by engineering experience, demonstrating that the proposed calculation method can effectively address the soil displacement calculation problem induced by the construction of non-horizontal parallel double-line shield tunnels and has good engineering applicability.

Abstract Background Virtual reality (VR) and augmented reality (AR) are emerging technologies that can be used for cardiopulmonary resuscitation (CPR) training. Compared to traditional face-to-face training, VR/AR-based training has the potential to reach a wider audience, but there is debate regarding its effectiveness in improving CPR quality. Therefore, we conducted a meta-analysis to assess the effectiveness of VR/AR training compared with face-to-face training. Methods We searched PubMed, Embase, Cochrane Library, Web of Science, CINAHL, China National Knowledge Infrastructure, and Wanfang databases from the inception of these databases up until December 1, 2023, for randomized controlled trials (RCTs) comparing VR- and AR-based CPR training to traditional face-to-face training. Cochrane's tool for assessing bias in RCTs was used to assess the methodological quality of the included studies. We pooled the data using a random-effects model with Review Manager 5.4, and assessed publication bias with Stata 11.0. Results Nine RCTs (involving 855 participants) were included, of which three were of low risk of bias. Meta-analyses showed no significant differences between VR/AR-based CPR training and face-to-face CPR training in terms of chest compression depth (mean difference [MD], -0.66 mm; 95% confidence interval [CI], -6.34 to 5.02 mm; P = 0.82), chest compression rate (MD, 3.60 compressions per minute; 95% CI, -1.21 to 8.41 compressions per minute; P = 0.14), overall CPR performance score (standardized mean difference, -0.05; 95% CI, -0.93 to 0.83; P = 0.91), as well as the proportion of participants meeting CPR depth criteria (risk ratio [RR], 0.79; 95% CI, 0.53 to 1.18; P = 0.26) and rate criteria (RR, 0.99; 95% CI, 0.72 to 1.35; P = 0.93). The Egger regression test showed no evidence of publication bias. Conclusions Our study showed evidence that VR/AR-based training was as effective as traditional face-to-face CPR training. Nevertheless, there was substantial heterogeneity among the included studies, which reduced confidence in the findings. Future studies need to establish standardized VR/AR-based CPR training protocols, evaluate the cost-effectiveness of this approach, and assess its impact on actual CPR performance in real-life scenarios and patient outcomes. Trial registration CRD42023482286.

The oxidation of methionyl peptides can contribute to increased biological (oxidative) stress and development of various inflammatory diseases. The conformation of peptides has an important role in the mechanism of oxidation and the intermediates formed in the reaction. Herein, the crystal structures of the isomeric dipeptides Gly-Met (Gly = glycine and Met = methionine) and Met-Gly, both C7H14N2O3S, are reported. Both molecules exist in the solid state as zwitterions with nominal proton transfer from the carboxylic acid to the primary amine group. The Gly-Met molecule has an extended backbone structure, while Met-Gly has two nearly planar regions kinked at the C atom bearing the NH3 group. In the crystals, both structures form extensive three-dimensional hydrogen-bonding networks via N—H...O and bifurcated N—H...(O,O) hydrogen bonds having N...O distances in the range 2.6619 (13)–2.8513 (13) Å for Gly-Met and 2.6273 (8)–3.1465 (8) Å for Met-Gly.

Ethiopia has made enormous efforts in the leather industry to gain manufacturing capabilities that can be scaled up to other sectors. Those efforts have resulted in the industry shifting its role from raw material supplier to producer of value-added products for the global supply chain (GSC). However, the industry has faced severe challenges in generating the expected revenue, utilizing capacity, and finally coping with the global competitive environment. Studies reveal that manufacturing firms tackle similar challenges by improving their supply chain performance (SCP). The challenges that appeared in the leather industry of Ethiopia could also be solved by improving its SCP. Nonetheless, there is a lack of study on the basic characteristics and SCP of the industry after it has shifted its role. The main objective of this study is, therefore, to measure the SCP to know where it stands using a bench mark and identify the elements that contribute considerably to the low overall SCP in order to lay the foundation for subsequent improvement. To achieve the research objective, data was collected from primary and secondary sources through a questionnaire, survey, observation, and focus group discussion. The data is analyzed using the supply chain operations reference model (SCOR version 12.0). Accordingly, the overall SCP is found to be 67.33%, suggesting an average rating as per the set benchmark. The source process is identified as the most influential element for the overall low SCP, with a percentage gap of 17.23%. Taking corrective action on the identified elements could help the industry overcome the existing challenges by improving its SCP.

Primary defects in two or more ectodermally-derived tissues during embryonic development characterize ectodermal dysplasia, a vast, varied group of inherited illnesses. Skin, hair, nails, eccrine glands, and teeth are the primary tissues affected. Most cases of ectodermal dysplasia are caused by the X-linked recessive form of the disease (also known as Christ–Siemens–Touraine syndrome), which is passed down from female carriers to their male offspring. It is characterized by an absence of sweat glands (hypohidrosis or anhidrosis), malformed teeth (anodontia or hypodontia), and scant hair (atrichosis or hypotrichosis). Lack of teeth and unusual look were cited as major causes for alarm. The usual manifestations of hypohidrotic hereditary ectodermal dysplasia have been described in two case reports. Two identical siblings with possible typically X-linked recessive hypohidrotic ectodermal dysplasia are described here. Despite the lack of a cure, patients can benefit from a multidisciplinary approach to treatment planning and an expedient diagnosis.

Abstract Whether the Main Himalayan Thrust can host a single surface-rupturing event in the Himalaya with a rupture length of > 700 km remains controversial. Previous paleoseismological studies in the Darjeeling-Sikkim Himalaya (DSH) suggested medieval surface-rupturing earthquakes, correlating them with the eleventh–thirteenth century events from Nepal and Bhutan and extending the coseismic rupture length > 700 km. Conversely, there is no rupture evidence of the 1714 Bhutan and 1934 Bihar–Nepal earthquakes in the DSH, resulting in a discrepancy in the rupture extent of the great earthquakes. Consequently, we conducted a paleoseismological investigation across a ~ 10 m-high fault scarp on the Himalayan Frontal Thrust at Chenga village, DSH, revealing a surface-faulting event during 1313–395 BCE. We suggest that the DSH is a 150 km-long independent segment bounded by a transverse ridge and fault and has a recurrence interval of ~ 949–1963 years, which is significantly larger than Nepal (~ 700–900 years) and Bhutan Himalaya (~ 339–761 years).

Changzhen Li,1,&ast; Xiaomei Wang,1,&ast; Jingjing Rao,1,&ast; Ye Zeng,1 Jianjun Liu,2 Feng Tang1 1Department of Laboratory Medicine, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430015, People’s Republic of China; 2Office of the Dean, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Feng Tang; Jianjun Liu, Email tang33feng66@163.com; liujianjun5221@163.comObjective: To analyze bacterial distribution and antibiotic resistance in clinical specimens from a Chinese hospital for evaluating environmental factors’ impact on pathogen prevalence.Methods: From January 2017 to December 2021, we collected 42,854 clinical specimens from hospitalized children and women. The specimens were cultured on various agar plates and incubated at 35°C for 18– 48 h. Their identification was performed using standard biochemical methods and Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF), whereas antibiotic susceptibilities were determined using the VITEK 2 system. Concurrent environmental data from Wuhan were analyzed for correlations with pathogen prevalence using multiple linear stepwise regression.Results: Of the 24,555 bacterial strains isolated, the majority were gram-positive, and sputum was the most common specimen type. Haemophilus influenzae and Escherichia coli were the most prevalent pathogens in sputum and urine samples, respectively. Notably, H. influenzae and Streptococcus pneumoniae affected children under 6 years of age the most. Furthermore, H. influenzae showed high ampicillin resistance but low cefotaxime resistance; S. pneumoniae was sensitive to penicillin G, and E. coli was resistant to ampicillin but sensitive to cefotetan. The prevalence of multidrug-resistant organisms was below national averages. In terms of seasonality, H. influenzae peaked during late winter and early spring, and environmental analysis indicated positive correlations between PM2.5 and PM10, and H. influenzae and S. pneumoniae prevalence. In addition, NO2 levels were positively correlated with increased S. aureus and M. catarrhalis prevalence; E coli prevalence was negatively correlated with ozone levels.Conclusion: This study provides valuable insights into the distribution and antibiotic resistance patterns of bacterial pathogens in maternal and child healthcare facilities in Wuhan, China. Environmental factors significantly influence the epidemiology of certain bacterial pathogens. Implementing integrated health strategies that combine microbial surveillance with environmental monitoring is needed to effectively manage and prevent bacterial infections.Keywords: epidemiology, multidrug-resistant pathogens, seasonality, particulate matter

C40H42O14N8Cl4Cd, triclinic, P1̄ (no. 2), a = 7.5892(16) Å, b = 7.6583(15) Å, c = 20.629(4) Å, α = 79.620(4)°, β = 84.594(3)°, γ = 79.427(4)°, V = 1157.0(4) Å3, Z = 1, R gt(F) = 0.0721, wR ref(F 2) = 0.1967, T = 296(2) K.

ObjectivesWilson’s disease is an autosomal recessive disorder related to copper metabolism which mostly patients occurs in adolescents, fertility has become a problem that WD needs to face.MethodsA 21 years retrospective follow up study was conducted and a total of 220 female patients were included to identify patients with outcomes of pregnancy.ResultsUntreated female patients with WD had a spontaneous abortion rate of 44%. During the study period, 146 female patients with WD from multicenter, 75 patients (51.4%) had successful outcomes of pregnancy. Notably, urinary copper levels below 616 μg/24 h were strongly associated with successful pregnancy. The nomogram built on these variables were age, urinary copper, haemoglobin and Child–Pugh classification, internally validated and showed good performance.ConclusionThe spontaneous abortion rate was 44% in untreated females with WD and developed a four-variable risk prediction model to accurately predict the likelihood of a successful pregnancy.

Thevetia peruviana (T. peruviana; Family: Apocynaceae), commonly known as Lucky Nut, is a traditionally and medicinally important plant, and the barks of the plant are traditionally used as anti-inflammatory, anti-diabetic, and antibacterial remedies. Thus, this study aimed to evaluate bioactive phytochemicals and in-vitro biological activities from the bark of T. peruviana using methanolic (TPM) and dichloromethane (TPD) extracts. The GC-MS analysis showed the presence of 54 and 39 bioactive compounds in TPM and TPD, respectively. The TPM extract has a higher level of total polyphenolic contents (TPC: 70.89 ± 1.08 and 51.07 ± 0.78 mg GAE/g extracts, while TFC: 56.89 ± 1.16 and 44.12 ± 1.76 Qu.E/g extracts for TPM and TPD, respectively). Herein, the results of antioxidant activities were also found in correlation with the total polyphenolic contents i.e., depicting the higher antioxidant potential of TPM compared to TPD. The significant inhibitory activities of extracts were observed against tyrosinase (TPM; 59.43 ± 2.87 %, TPD; 53.43 ± 2.65 %), lipoxygenase (TPM; 77.1 ± 1.2 %, TPD; 59.3 ± 0.1 %), and α-glucosidase (TPM; 71.32 ± 2.44 %, TPD; 67.86 ± 3.011 %). Furthermore, in comparison to co-amoxiclave, the antibacterial property against five bacterial strains was significant assayed. The compounds obtained through GC-MS analysis were subjected to in-silico molecular docking studies, and the phyto-constituents with maximum binding scores were then subjected to ADME analysis. The results of in-silico studies revealed that the binding affinity of several phyto-constituents was even greater than that of the standard inhibitory ligands. ADME analysis showed bioavailability radars of phyto-constituents having maximum docking scores in molecular docking. The results of this study indicated that T. peruviana has bioactive phytochemicals and therapeutic potential and may provide a basis for treating metabolic disorders (inflammatory diseases like rheumatism and diabetes), bacterial infections, and skin-related problems.

[ Objective ] This study aims to explore the regulatory mechanism of SnRK2 family members un- der drought stress in Saccharum spontaneum L. , in order to provide candidate genes for cultivating drought resistant sugarcane varieties. [ Methods ] This study identified SnRK2 genes in S . spontaneum L. based on whole genome data , and conducted bioinformatics analysis and expression analysis under drought stress. [ Results ] 11 SnRK2 members were identified and named as SsSnRK2 . 1 to SsSnRK2 . 11 , which were unevenly distributed on 8 chromosomes. The amino acid residues of SsSnRK2s were ranged from 227 to 580 , the molecular weights were from 25 683.53 kD to 64 695.8 kD , the isoelectric points were from 4.62 to 8.94 , and all were hydrophilic proteins. The 11 SsSnRK2s could be divided into 3 subgroups , and the conserved motif sequences within the same subgroup were highly similar , with the number of exons ranging from 7 to 9. The promoters of SsSnRK2 members contained various hormone-related and abiotic stress responsive elements. SsSnRK2 members were expressed in a tissue-specific manner. All SsSnRK2 genes were able to respond to drought stress to various degrees. [ Conclusion ] The SsSnRK2 family plays a significant role in response to drought stress , providing a basis for the study of stress resistance in S . spontaneum L..

Phase decomposition can effectively enhance the mechanical properties of carbide ceramics and can overcome the difficulty of enhancing the mechanical properties of single-phase multicomponent carbide ceramics. In this work, a series of nonstoichiometric (TiZrVNb)Cx ceramics were prepared by spark plasma sintering (SPS) at different temperatures. The effects of the carbon content on the phase composition, microstructure evolution, and mechanical properties were investigated in detail. Phase decomposition occurred with decreasing carbon content. Two different solid solutions of (Ti,V)-rich and Zr-rich phases formed from the decomposition of equimolar single-phase solid solutions, namely, the Zr-poor phase and Zr-rich phase, respectively. The distribution of Nb element is relatively uniform. The semicoherent interfaces between the Zr-poor phase and the Zr-rich phase can harden and strengthen effectively under the synergistic effect of grain refinement. Ceramics with phase decomposition structures have apparent advantages compared to single-phase high-entropy carbides. This work provides an important train of thought for the microstructure tailoring and properties optimization of multi-component carbide ceramics.

ObjectiveCamellia oleifera is one of the four major woody oil plants in the world. Diseases is a significant factor leading to the decline in quality of Camellia oleifera and the financial loss of farmers. Among these diseases, anthracnose is a common and severe disease in Camellia oleifera forests, directly impacting yields and production rates. Accurate disease assessment can improve the prevention and control efficiency and safeguarding the farmers' profit. In this study, an improved You Only Look at CoefficienTs (YOLACT) based method was proposed to realize automatic and efficient grading of the severity of Camellia oleifera leaf anthracnose.MethodsHigh-resolution images of Camellia oleifera anthracnose leaves were collected using a smartphone at the National Camellia oleifera Seed Base of Jiangxi Academy of Forestry, and finally 975 valid images were retained after a rigorous screening process. Five data enhancement means were applied, and a data set of 5 850 images was constructed finally, which was divided into training, validation, and test sets in a ratio of 7:2:1. For model selection, the Camellia-YOLACT model was proposed based on the YOLACT instance segmentation model, and by introducing improvements such as Swin-Transformer, weighted bi-directional feature pyramid network, and HardSwish activation function. The Swin Transformer was utilized for feature extraction in the backbone network part of YOLACT, leveraging the global receptive field and shift window properties of the self-attention mechanism in the Transformer architecture to enhance feature extraction capabilities. Additionally, a weighted bidirectional feature pyramid network was introduced to fuse feature information from different scales to improve the detection ability of the model for objects at different scales, thereby improving the detection accuracy. Furthermore, to increase the the model's robustness against the noise in the input data, the HardSwish activation function with stronger nonlinear capability was adopted to replace the ReLu activation function of the original model. Since images in natural environments usually have complex background and foreground information, the robustness of HardSwish helped the model better handling these situations and further improving the detection accuracy. With the above improvements, the Camellia-YOLACT model was constructed and experimentally validated by testing the Camellia oleifera anthracnose leaf image dataset.Results and DiscussionsA transfer learning approach was used for experimental validation on the Camellia oleifera anthracnose severity grading dataset, and the results of the ablation experiments showed that the mAP75 of Camellia-YOLACT proposed in this study was 86.8%, mAPall was 78.3%, mAR was 91.6% which were 5.7%, 2.5% and 7.9% higher than YOLACT model. In the comparison experiments, Camellia-YOLACT performed better than Segmenting Objects by Locations (SOLO) in terms of both accuracy and speed, and its detection speed was doubled compared to Mask R-CNN algorithm. Therefore, the Camellia-YOLACT algorithm was suitable in Camellia oleifera gardens for anthracnose real-time segmentation. In order to verify the outdoors detection performance of Camellia-YOLACT model, 36 groups of Camellia oleifera anthracnose grading experiments were conducted. Experimental results showed that the grading correctness of Camellia oleifera anthracnose injection severity reached 94.4%, and the average absolute error of K-value was 1.09%. Therefore, the Camellia-YOLACT model proposed in this study has a better performance on the grading of the severity of Camellia oleifera anthracnose.ConclusionsThe Camellia-YOLACT model proposed got high accuracy in leaf and anthracnose segmentation of Camellia oleifera, on the basis of which it can realize automatic grading of the severity of Camellia oleifera anthracnose. This research could provide technical support for the precise control of Camellia oleifera diseases.

[Objective] The targeted poverty alleviation program has, overall, elevated the social welfare of impoverished households. However, the role of the targeted poverty alleviation program plays in improving households’ relative welfare, such as relative deprivation of consumption, remains a subject for discussion. The answer to this question carries significant implications for improving the quality and efficiency of government assistance policies. [Methods] Based on the China Household Finance Survey (CHFS) data from 2013 to 2019, this study calculated the relative deprivation of household consumption using the Kakwani index for the surveyed households residing in a city (or province). Then, using the difference-in-differences method, this study examined the impact of the targeted poverty alleviation program on the relative consumption deprivation of poor households. Finally, employing heterogeneity analysis of the causes of poverty, as well as consumption categorization and an interactive model of poverty alleviation styles, this study tested the effect of the government targeted poverty alleviation program on the relative deprivation of household consumptions. [Results] The targeted poverty alleviation program has generally reduced the relative deprivation of consumption for impoverished households, albeit having a relatively weak economic effect. This result remains valid even after a series of placebo-tests and regressing on a matched sample set. Further classification and scrutiny of the consumption types, poverty alleviation styles, and causes of poverty revealed that poverty-stricken households experienced a significant reduction in relative deprivation of consumption in the healthcare expenditure and education expenditure. This is because the welfare type poverty alleviation policies such as medical support, housing and living assistance, and children’s education support significantly enhanced the consumption welfare of poor households. However, no statistically significant effect was found in other development assistance type poverty alleviation policies. [Conclusion] The impact of the targeted poverty alleviation program on household relative consumption deprivation was generally weak, and was concentrated in protection-oriented poverty alleviation policies, such as medical support and educational assistance. In the future, government assistance needs to enhance efficiency and optimization in development-oriented policies.

Geochemistry of noble gases has been applied to the study of deep Earth materials and celestial meteorites. With advancements in measurement technology, it is also increasingly being used in natural gas research. Using the most advanced noble gas mass spectrometer, a systematic analysis was conducted on the abundance and isotopes of noble gas samples collected from the middle and deep Songliao Basin in eastern China to elucidate the compositional characteristics of noble gases in a faulted basin. The findings reveal that the abundance of noble gases in natural gas decreases from light noble gases to heavy noble gases in a left-to-right reversed L-shaped pattern. Specifically, the isotopic ratios of noble gases are: 3He/4He at 2.64×10-6, 20Ne/22Ne at 9.94, 21Ne/22Ne at 0.029 22, and 40Ar/36Ar at 743.7, all of which are higher than atmospheric values. The isotopes 80Kr, 84Kr, 86Kr, and 131-136Xe show relative excess compared to atmospheric levels, indicating the mixing of mantle-derived gases in the natural gas. Based on the compositional characteristics of noble gases, this study suggests that the natural gas in the middle and deep Songliao Basin originated from inorganic crust and mantle mixing. Additionally, certain differences exist in the contribution of mantle-derived components across different tectonic blocks and categories of natural gas within the basin. Comparison between noble gas compositions and the types of natural gas demonstrates that light noble gases distinguish effectively between different types of natural gas, whereas the composition of heavy noble gases shows no significant differences among various types of natural gas. Noble gas isotopes, in addition to tracing the source of natural gas, can also be used to determine natural gas genesis, distinguish natural gas types and characterize tectonic settings.

Abstract Background Observational studies have reported that gut microbiota composition is associated with metabolic syndrome. However, the causal effect of gut microbiota on metabolic syndrome has yet to be confirmed. Methods We performed a bidirectional Mendelian randomization study to investigate the causal effect between gut microbiota and metabolic syndrome in European population. Summary statistics of gut microbiota were from the largest available genome-wide association study meta-analysis (n = 13,266) conducted by the MiBioGen consortium. The summary statistics of outcome were obtained from the most comprehensive genome-wide association studies of metabolic syndrome (n = 291,107). The inverse-variance weighted method was applied as the primary method, and the robustness of the results was assessed by a series of sensitivity analyses. Results In the primary causal estimates, Actinobacteria (OR = 0.935, 95% CI = 0.878–0.996, P = 0.037), Bifidobacteriales (OR = 0.928, 95% CI = 0.868–0.992, P = 0.028), Bifidobacteriaceae (OR = 0.928, 95% CI = 0.868–0.992, P = 0.028), Desulfovibrio (OR = 0.920, 95% CI = 0.869–0.975, P = 0.005), and RuminococcaceaeUCG010 (OR = 0.882, 95% CI = 0.803–0.969, P = 0.009) may be associated with a lower risk of metabolic syndrome, while Lachnospiraceae (OR = 1.130, 95% CI = 1.016–1.257, P = 0.025), Veillonellaceae (OR = 1.055, 95% CI = 1.004–1.108, P = 0.034) and Olsenella (OR = 1.046, 95% CI = 1.009–1.085, P = 0.015) may be linked to a higher risk for metabolic syndrome. Reverse MR analysis demonstrated that abundance of RuminococcaceaeUCG010 (OR = 0.938, 95% CI = 0.886–0.994, P = 0.030) may be downregulated by metabolic syndrome. Sensitivity analyses indicated no heterogeneity or horizontal pleiotropy. Conclusions Our Mendelian randomization study provided causal relationship between specific gut microbiota and metabolic syndrome, which might provide new insights into the potential pathogenic mechanisms of gut microbiota in metabolic syndrome and the assignment of effective therapeutic strategies.

Rui Han,1,2 Xiwu Rao,3 Huiling Zhou,4 Lingeng Lu5– 7 1Department of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai, People’s Republic of China; 2Department of Chinese Medicine, Naval Medical University, Shanghai, People’s Republic of China; 3Department of Oncology, The First Hospital Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 4Department of Oncology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, People’s Republic of China; 5Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA; 6School of Medicine, Center for Biomedical Data Science, Yale University, New Haven, CT, USA; 7Yale Cancer Center, Yale University, New Haven, CT, USACorrespondence: Rui Han, Department of Chinese Medicine Oncology, The First Affiliated Hospital of Naval Medical University, Shanghai, 200433, People’s Republic of China, Email dianxiqiao@foxmail.comAbstract: The utilization of PD-1/PD-L1 inhibitors marks a significant advancement in cancer therapy. However, the efficacy of monotherapy is still disappointing in a substantial subset of patients, necessitating the exploration of combinational strategies. Emerging from the promising results of the KEYNOTE-942 trial, RNA-based therapies, particularly circRNAs and piRNAs, have distinguished themselves as innovative sensitizers to immune checkpoint inhibitors (ICIs). These non-coding RNAs, notable for their stability and specificity, were once underrecognized but are now known for their crucial roles in regulating PD-L1 expression and bolstering anti-cancer immunity. Our manuscript offers a comprehensive analysis of selected circRNAs and piRNAs, elucidating their immunomodulatory effects and mechanisms, thus underscoring their potential as ICIs enhancers. In conjunction with the recent Nobel Prize-awarded advancements in mRNA vaccine technology, our review highlights the transformative implications of these findings for cancer treatment. We also discuss the prospects of circRNAs and piRNAs in future therapeutic applications and research. This study pioneers the synergistic application of circRNAs and piRNAs as novel sensitizers to augment PD-1/PD-L1 inhibition therapy, demonstrating their unique roles in regulating PD-L1 expression and modulating immune responses. Our findings offer a groundbreaking approach for enhancing the efficacy of cancer immunotherapy, opening new avenues for treatment strategies. This abstract aims to encapsulate the essence of our research and the burgeoning role of these non-coding RNAs in enhancing PD-1/PD-L1 inhibition therapy, encouraging further investigation into this promising field.Keywords: CircRNA, piwi-RNA, immunotherapy, PD-1/PD-L1 blockade, immunotherapy sensitizer, combination therapy