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Abstract Background Sex disparity between metabolic-obesity (defined by body mass index, BMI) phenotypes and obesity-related cancer (ORC) remains unknown. Considering BMI reflecting overall obesity but not fat distribution, we aimed to systematically assess the association of our newly proposed metabolic-anthropometric phenotypes with risk of overall and site-specific ORC by sex. Methods A total of 141,579 men (mean age: 56.37 years, mean follow-up time: 12.04 years) and 131,047 women (mean age: 56.22 years, mean follow up time: 11.82 years) from the UK Biobank was included, and designated as metabolic-anthropometric phenotypes based on metabolic status (metabolically healthy/unhealthy), BMI (non-obesity/obesity) and body shape (pear/slim/apple/wide). The sex-specific association of different phenotypes with overall and site-specific ORC was assessed by hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression models. Results We found metabolically unhealthy and/or obesity phenotypes conveyed a higher risk in men than in women for overall ORC and colorectal cancer compared with metabolically healthy non-obesity phenotype (P interaction

AIM:To investigate the relationship among lens parameters and their correlation with ocular anatomic characteristics in myopia patients implanted with posterior-chamber phakic implantable collamer lens(Phakic-ICL).METHODS:Retrospective study. A total of 46 myopia patients(46 eyes)who underwent Phakic-ICL implantation were collected in the Wuxi Huaxia Eye Hospital from June 2022 to June 2023. Preoperative evaluation of ocular anatomical characteristics included corneal central thickness(CCT), anterior chamber depth(ACD), axial length(AL), white-to-white(WTW), horizontal sulcus to sulcus(STSH), horizontal angle to angle(ATAH), and vertical sulcus to sulcus(STSV), vertical angle to angle(ATAV). Furthermore, lens parameters included horizontal crystalline lens rise(CLRH), vertical CLR(CLRV)and vertical lens thickness(LTV). The difference, consistency and correlation of the above parameters were analyzed.RESULTS:Except for differences between WTW and STSV, STSH and ATAV, which were not statistically significant(all P>0.05), the other horizontal and vertical ocular anatomical characteristics were statistically significant(P0.05). Bland-Altman results revealed that the anatomical characteristics in the horizontal or vertical diameters showed poor consistency. The consistency between CLRH and CLRV was poor. There was consistency between LTH and LTV, with the 95% limits of agreement(LoA)between the differences ranging from -0.21 to 0.28 mm, and the proportion of out-of-line points off the 95% LoA was 4.35%. Pearson correlation analysis revealed that there were correlations between the anatomical characteristics of the horizontal and vertical diameters(P0.05). There were correlations between the lens parameters(P0.05). Multiple linear regression analysis revealed that LT=0.419+0.017×age-0.548×ACD+0.371×ATAH+0.884×CLRV, CLRH=-0.443+0.809×CLRV, CLRV=-0.092-0.200×ATAH+0.560×CLRH(corrected R2=0.458, 0.482, 0.589, respectively).CONCLUSION:Horizontal and vertical diameters were not interchangeable. CLRH and CLRV were not interchangeable, while LTH and LTV were interchangeable. Partial lens parameters, WTW, STS, and ATA were correlated with ACD. Finally, age, ACD, ATAH, and CLRV influenced LT.

Abstract Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor expressed predominantly in NK and T-cell subsets that downregulates the activation and proliferation of immune cells and participates in cell-mediated immune responses. Accumulating evidence has demonstrated the importance of KLRG1 as a noteworthy disease marker and therapeutic target that can influence disease onset, progression, and prognosis. Blocking KLRG1 has been shown to effectively mitigate the effects of downregulation in various mouse tumor models, including solid tumors and hematologic malignancies. However, KLRG1 inhibitors have not yet been approved for human use, and the understanding of KLRG1 expression and its mechanism of action in various diseases remains incomplete. In this review, we explore alterations in the distribution, structure, and signaling pathways of KLRG1 in immune cells and summarize its expression patterns and roles in the development and progression of autoimmune diseases, infectious diseases, and cancers. Additionally, we discuss the potential applications of KLRG1 as a tool for tumor immunotherapy.

Abstract Background The study aimed to explore the relationship between low-density lipoprotein cholesterol (LDL-C) genetic variants and obstructive sleep apnea (OSA) and its complications, including cardiovascular diseases (CVD), insulin resistance (IR), and metabolic syndrome (MS). Method 4329 individuals with suspected OSA who underwent a comprehensive assessment of anthropometric, biochemical, and polysomnography (PSG) data, along with 30 LDL-C single nucleotide polymorphisms (SNPs) were enrolled. The 10-year Framingham CVD risk score (FRS), IR and MS were evaluated for each subject. Linear regression and logistic regression were utilized to examine the correlations among these variables. Results After the Benjamini-Hochberg correction, linear regression results indicated positive correlations between variants rs3741297 and rs629301 with FRS (β = 0.031, PBH=0.002; β = 0.026, PBH=0.015). Logistic regression revealed that rs3741297 increased MS risk among total subjects [OR = 1.67 (95% CI:1.369–2.038), PBH=1.32 × 10− 5] and increased IR risk in females [OR = 3.475 (95% CI:1.653–7.307), PBH=0.03]. In males, rs2642438 decreased MS risk [OR = 0.81 (95% CI:0.703–0.933), PBH=0.045]. Conclusions The rs3741297 variant correlated with susceptibility to CVD, IR, and MS in the OSA population. OSA, CVD, IR and MS share a potentially common genetic background, which may promote precision medicine. Cinical trial registration The study protocol was registered with the Chinese Clinical Trial Registry (ChiCTR1900025714).

Abstract Tripartite motif 8 (TRIM8) is an E3 ligase that plays dual roles in various tumor types. The biological effects and underlying mechanism of TRIM8 in hepatocellular carcinoma (HCC) remain unknown. Hepatocyte nuclear factor 1α (HNF1α) is a key transcriptional factor that plays a significant role in regulating hepatocyte differentiation and liver function. The reduced expression of HNF1α is a critical event in the development of HCC, but the underlying mechanism for its degradation remains elusive. In this study, we discovered that the expression of TRIM8 was upregulated in HCC tissues, and was positively correlated with aggressive tumor behavior of HCC and shorter survival of HCC patients. Overexpression of TRIM8 promoted the proliferation, colony formation, invasion, and migration of HCC cells, while TRIM8 knockdown or knockout exerted the opposite effects. RNA sequencing revealed that TRIM8 knockout suppresses several cancer-related pathways, including Wnt/β-catenin and TGF-β signaling in HepG2 cells. TRIM8 directly interacts with HNF1α, promoting its degradation by catalyzing polyubiquitination on lysine 197 in HCC cells. Moreover, the cancer-promoting effects of TRIM8 in HCC were abolished by the HNF1α-K197R mutant in vitro and in vivo. These data demonstrated that TRIM8 plays an oncogenic role in HCC progression through mediating the ubiquitination of HNF1α and promoting its protein degradation, and suggests targeting TRIM8-HNF1α may provide a promising therapeutic strategy of HCC.

Abstract This longitudinal study in Mainland China (2021–2022) explored the impact of adverse childhood experiences (ACEs) on complex posttraumatic stress disorder (CPTSD) symptoms, with a focus on the role of self-compassion. Among 18,933 surveyed university students, 21.2% reported experiencing at least one ACE. Results revealed a clear relationship between ACEs and CPTSD symptoms. Furthermore, self-compassion, particularly the dimensions of self-judgment and isolation, moderated the association between retrospective ACEs and posttraumatic stress disorder (PTSD) and disturbance in self-organization (DSO) symptoms. These findings highlight the enduring impact of ACEs on CPTSD symptoms and emphasize the importance of early identification and targeted interventions, especially addressing self-judgment and isolation, to mitigate CPTSD risk among young Chinese adults.

Highly homogeneous magnetic fields in magnetic resonance spectrometers are an important guarantee for improving the quality of spectra for chemical structure analysis and kinetic information. The active shimming process using a shimming power supply to drive a shimming coil to produce a compensating electromagnetic field is an essential way to improve the homogeneity of the magnetic field. The high accuracy and stability of the shimming power supply’s output are crucial indicators for improving the active shimming capability and maintaining the shimming results. The paper develops a high-precision, high-stability, low-ripple active shimming power supply system for magnetic resonance spectrometers, and designs a shimming current driver (constant current source) with output state monitoring based on negative feedback control, coupled with an MCU control platform and host computer system to complete the closed-loop transmission of control commands and data between hardware and software, to achieve digital constant current output control. Under R=2.84 Ω, L=25.5 µH shimming coil load, the full-scale output response time is less than 18.9 µs, the output ripple peak-to-peak control is 30 mV, the positive and negative current output symmetry is good, and the maximum output deviation is 4.8‰ for long time operation. This power supply was used in a nuclear magnetic resonance spectrometer system using 0.5 T-Halbach configuration magnets, and the magnetic field homogeneity was optimised from 24.48 ppm (10-6) to 2.72 ppm by driving a first-order shimming coil. This work contributes to the integration of compact nuclear magnetic resonance spectrometer systems and the applications related to active shimming.

BACKGROUND: The current understanding of the correlation between TLR4 gene (toll-like receptor 4) rs4986790 and rs4986791 polymorphisms and asthma susceptibility is inconclusive, with studies and populations yielding conflicting results. OBJECTIVES: Evaluate this relationship using meta-analysis and trial sequential analysis (TSA). PATIENTS AND METHODS: Databases were systematically queried for relevant articles from the establishment of the database to 19 June 2023 adhering to predefined inclusion and exclusion criteria. Two authors independently conducted screening, data extraction, and quality evaluation. Meta-analysis and TSA were carried out using RevMan 5.4, StataMP 17.0, and TSA 0.9.5.10 Beta, with α=0.05. Subgroup analyses were conducted based on racial demographics. A sensitivity analysis was conducted employing a one-by-one exclusion method. Publication bias was assessed using the Begg and Egger tests. MAIN OUTCOME MEASURES: Association of asthma susceptibility with TLR4 gene rs4986790 and rs4986791 polymorphisms. SAMPLE SIZE: 23 articles included 22 studies on the rs4986790 polymorphism and 11 studies on the rs4986791 polymorphism on the TLR4 gene. RESULTS: Out of 692 studies screened, 23 met the inclusion criteria. While the overall meta-analysis showed no significant association between the TLR4 rs4986790 polymorphism and asthma susceptibility, subgroup analysis revealed a significant link in the Caucasian population. A significant association was noted in the meta-analysis, particularly among Asian populations, on the rs4986791 polymorphism. The sensitivity analysis indicated that the meta-analysis results were relatively stable. Publication bias analysis revealed minimal influence from publication bias. However, TSA was underscored by the necessity for additional original studies to further validate specific outcomes. CONCLUSIONS: Our study underscores the ethnicity-specific impact on the relationship between TLR4 polymorphisms and asthma susceptibility. While the overall findings for rs4986790 were not significant, the association with the Caucasian population merits further investigation. Furthermore, rs4986791 demonstrated a significant correlation with asthma susceptibility, specifically among Asian populations. LIMITATIONS: Our study predominantly examined the rs4986790 and rs4986791 polymorphisms, overlooking the potential influence of other genetic variants within TLR4.

Abstract Background Dysbiosis of the gut microbiota is pivotal in Crohn’s disease (CD) and modulated by host physiological conditions. Hyperbaric oxygen therapy (HBOT) is a promising treatment for CD that can regulate gut microbiota. The relationship between HBOT and the gut microbiota in CD remains unknown. Methods CD patients were divided into an HBOT group (n = 10) and a control group (n = 10) in this open-label prospective interventional study. The fecal samples before and after HBOT were used for 16 S rRNA gene sequencing and fecal microbiota transplantation (FMT). A colitis mouse model was constructed using dextran sulfate sodium, and intestinal and systematic inflammation was evaluated. The safety and long-term effect of HBOT were observed. Results HBOT significantly reduced the level of C-reactive protein (CRP) (80.79 ± 42.05 mg/L vs. 33.32 ± 18.31 mg/L, P = 0.004) and the Crohn’s Disease Activity Index (CDAI) (274.87 ± 65.54 vs. 221.54 ± 41.89, P = 0.044). HBOT elevated the declined microbial diversity and ameliorated the altered composition of gut microbiota in patients with CD. The relative abundance of Escherichia decreased, and that of Bifidobacterium and Clostridium XIVa increased after HBOT. Mice receiving FMT from donors after HBOT had significantly less intestinal inflammation and serum CRP than the group before HBOT. HBOT was safe and well-tolerated by patients with CD. Combined with ustekinumab, more patients treated with HBOT achieved clinical response (30%vs.70%, P = 0.089) and remission (20%vs.50%, P = 0.160) at week 4. Conclusions HBOT modulates the dysbiosis of gut microbiota in CD and ameliorates intestinal and systematic inflammation. HBOT is a safe option for CD and exhibits a promising auxiliary effect to ustekinumab. Trial registration Chinese Clinical Trial Registry, ChiCTR2200061193. Registered 15 June 2022, https://www.chictr.org.cn/showproj.html?proj=171605 .

Abstract Background The pathway involving PTEN-induced putative kinase 1 (PINK1) and PARKIN plays a crucial role in mitophagy, a process activated by artesunate (ART). We propose that patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis exhibit insufficient mitophagy, and ART enhances mitophagy via the PINK1/PARKIN pathway, thereby providing neuroprotection. Methods Adult female mice aged 8–10 weeks were selected to create a passive transfer model of anti-NMDAR encephalitis. We conducted behavioral tests on these mice within a set timeframe. Techniques such as immunohistochemistry, immunofluorescence, and western blotting were employed to assess markers including PINK1, PARKIN, LC3B, p62, caspase3, and cleaved caspase3. The TUNEL assay was utilized to detect neuronal apoptosis, while transmission electron microscopy (TEM) was used to examine mitochondrial autophagosomes. Primary hippocampal neurons were cultured, treated, and then analyzed through immunofluorescence for mtDNA, mtROS, TMRM. Results In comparison to the control group, mitophagy levels in the experimental group were not significantly altered, yet there was a notable increase in apoptotic neurons. Furthermore, markers indicative of mitochondrial leakage and damage were found to be elevated in the experimental group compared to the control group, but these markers showed improvement following ART treatment. ART was effective in activating the PINK1/PARKIN pathway, enhancing mitophagy, and diminishing neuronal apoptosis. Behavioral assessments revealed that ART ameliorated symptoms in mice with anti-NMDAR encephalitis in the passive transfer model (PTM). The knockdown of PINK1 led to a reduction in mitophagy levels, and subsequent ART intervention did not alleviate symptoms in the anti-NMDAR encephalitis PTM mice, indicating that ART’s therapeutic efficacy is mediated through the activation of the PINK1/PARKIN pathway. Conclusions At the onset of anti-NMDAR encephalitis, mitochondrial damage is observed; however, this damage is mitigated by the activation of mitophagy via the PINK1/PARKIN pathway. This regulatory feedback mechanism facilitates the removal of damaged mitochondria, prevents neuronal apoptosis, and consequently safeguards neural tissue. ART activates the PINK1/PARKIN pathway to enhance mitophagy, thereby exerting neuroprotective effects and may achieve therapeutic goals in treating anti-NMDAR encephalitis.

Abstract Objectives Obstructive sleep apnea (OSA) is associated with abnormal glucose and lipid metabolism. However, whether there is an independent association between Sleep Apnea-Specific Hypoxic Burden (SASHB) and glycolipid metabolism disorders in patients with OSA is unknown. Methods We enrolled 2,173 participants with suspected OSA from January 2019 to July 2023 in this study. Polysomnographic variables, biochemical indicators, and physical measurements were collected from each participant. Multiple linear regression analyses were used to evaluate independent associations between SASHB, AHI, CT90 and glucose as well as lipid profile. Furthermore, logistic regressions were used to determine the odds ratios (ORs) for abnormal glucose and lipid metabolism across various SASHB, AHI, CT90 quartiles. Results The SASHB was independently associated with fasting blood glucose (FBG) (β = 0.058, P = 0.016), fasting insulin (FIN) (β = 0.073, P

Crohn’s disease is a chronic intestinal inflammatory disorder of unknown etiology. Although the pharmacotherapies for Crohn’s disease are constantly updating, nutritional support and adjuvant therapies have recently gained more attention. Due to advancements in clinical nutrition, various clinical nutritional therapies are used to treat Crohn’s disease. Doctors treating inflammatory bowel disease can now offer several diets with more flexibility than ever. The Crohn’s disease exclusion diet is a widely used diet for patients with active Crohn’s disease. The Crohn’s disease exclusion diet requires both exclusion and inclusion. Periodic exclusion of harmful foods and inclusion of wholesome foods gradually improves a patient’s nutritional status. This article reviews the Crohn’s disease exclusion diet, including its structure, mechanisms, research findings, and clinical applications.

MXenes, as promising two-dimensional (2D) transition metal carbides or nitrides, are a promising new family of 2D materials. MXenes have superior electrical conductivity, a unique accordion-like structure, excellent mechanical properties and abundant surface termination, which make them the preferred material for the ever-growing market of energy storage, adsorption, gas sensing and other fields. As one of the typical representatives of the MXene family, Tin+1NnTx MXene is notable due to its high conductivity, high specific capacitance, high catalytic activity and low precursor cost compared to other MXenes and can be used for clean energy storage and catalysis applications. However, relatively little is currently known about the MXene Tin+1NnTx, and a special review on the synthesis, properties, and applications of Tin+1NnTx has not been reported to date. Herein, we overview and introduce the synthesis progress, application and properties of MXene Tin+1NnTx. The major problems and bottlenecks are objectively dissected and evaluated. In addition, future viewpoints and research opportunities are presented for the development of advanced MXene and MXene-based materials.

Carbon nano additives (CNAs) are critical to achieving the unique properties of functionalized composites, however, controlling the dispersion of CNAs in material matrix is always a challenging task. In this study, a simple atomization approach was successfully developed to promote the dispersion efficiency of graphene nanoplatelets (GNPs) in cement composites. This atomization approach can be integrated with the direct, indirect and combined ultrasonic stirrings in a homemade automatic stirring-atomization device. Mechanical and microstructure tests were performed on hardened cement pastes blended with GNPs in different stirring and mixing approaches. Results show that the direct ultrasonic stirrings enabled more homogeneous dispersions of GNP particles with a smaller size for a longer duration. The atomized droplets with the mean size of ∼100 ​μm largely mitigated GNPs’ agglomerations. Monolayer GNPs were observed in the cement matrix with the strength gain by up to 54%, and the total porosity decrease by 21% in 0.3 ​wt% GNPs dosage. The greatly enhanced dispersion efficiency of GNPs in cement also raised the cement hydration. This work provides an effective and manpower saving technique toward dispersing CNAs in engineering materials with great industrialization prospects.

The impact of cadmium (Cd) toxicity on fish liver injury has received much attention in recent years. Currently, autophagy, apoptosis and endoplasmic reticulum stress were reported in Cd exposed fish liver, and if there are other mechanisms (such as ferroptosis) and relevant signaling pathways involved in fish remains unknown. An experiment was conducted to investigate Cd toxicity in Channa argus (Cantor, 1842) exposed to 0, 1.0, and 2.0 mg Cd/L of water for 96 h. Cd disrupted the structure of mitochondria in the liver. Besides, Cd induced ferroptosis by significantly increasing the level of Fe2+, ROS, MDA and significantly decreasing the level of Ferritin, GSH, GSH-Px, GPX4, GST and SOD (p < 0.05 in all cases). In addition, the mRNA expression of ferroptosis related genes, gpx4 and slc7a11, were significantly downregulated by Cd. Moreover, Cd exposure significantly inhibited the Nrf2/Keap1 signaling pathway, one of the pathways involved in ferroptosis, by upregulating the mRNA levels of keap1a and keap1b, and downregulating the mRNA levels of nrf2 and its target genes (ho-1, nqo1 and cat). Cd exposure also caused extensive accumulation of vacuoles and lipid droplets in liver, as well as an increase in triglyceride content. Cd significantly affected lipid metabolism related enzyme activity and gene expression, which were also regulated by Nrf2/Keap1 signaling pathway. In summary, these results indicate that ferroptosis is a mechanism in waterborne Cd exposed fish liver injury via the Nrf2/Keap1 signaling pathway and the Cd induced hepatic steatosis is also modulated by Nrf2/Keap1 pathway at the whole-body level in fish. These findings provide new insights into the fish liver injury and molecular basis of Cd toxicity.

Background: One of the most prevalent causes of death in sepsis is sepsis-induced cardiomyopathy (SICM). Circadian disruption is involved in the progress of sepsis. However, the molecular mechanism remains unclear. Methods: Here, we built LPS-induced SICM in-vivo and in-vitro models. LPS was administrated at the particular Zeitgeber times (ZT), ZT4-ZT10-ZT16-ZT22 and ZT10-ZT22 in vivo and vitro experiments, respectively. Results: In vivo experiment, injection of LPS at ZT10 induced higher infiltration of inflammatory cells and content of intracellular Fe2+, and lower level of Glutathione peroxidase 4 (GPX4) and cardiac function than other ZTs (P

The model of the diffusion bonding pressure was established using the analysis calculation method and further verified by the finite element analysis (FEA) and the experiments. The normalized temperature was defined as the ratio of temperature and the melting point of the base materials. And the normalized bonding pressure was defined as the ratio of the applied bonding pressure and the yield strength at the bonding temperature. The contribution of the plastic deformation to the void closure expressed a linear relationship with the normalized bonding pressure, of which the slope was 3. The relationship was appropriate in TiAl6V4, pure copper C11000, aluminium alloy AA6061, stainless steel SUS 304, and Ni-based alloy Inconel 617 using analysis calculation. The diffusion bonding pressure design range can be summarized as σn = 0.05–0.577. Subsequently, the analytic computational model was verified by FEA. The results showed that the maximum stress was concentrated in the position of the void neck. And the linear relationship between the normalized bonding pressure and the bonded ratio was also tenable. There was a stable static error existed between FEA and the analytic computational analysis. Furthermore, the experimental verification showed the verification and accuracy of the analytic computational analysis results.

Background:Cordyceps sinensis is a traditional Chinese medicine that has shown promise for the management of chronic bronchitis (CB). We aim to assess the efficacy and safety of a preparation of C sinensis named Bailing capsule (Hirsutella sinensis, Cs-C-Q80) compared with a placebo in patients with CB.Methods: This randomized, double-blind, placebo-controlled, parallel-group clinical trial (Chinese Clinical Trial Registry; registration number: ChiCTR1900025707) recruited patients with CB from eight hospitals in China between May 2019 and December 2020. Patients were randomized 2:1 to receive Bailing capsule or a placebo orally for 48 weeks (2.0 g, three times a day).Results: Among 240 patients who were randomized, 238 (Bailing capsule: 159, placebo: 79) were included in the primary analysis. Bailing capsule significantly reduced the frequency of acute exacerbation of CB (AECB) compared with the placebo during treatment (0.43 ± 0.82 vs. 1.56 ± 1.34; P < 0.001) and follow-up (0.21 ± 0.64 vs. 0.45 ± 0.93; P = 0.026). Bailing capsule improved the severity of expectoration (P = 0.046) and wheezing (P = 0.010) in AECB during follow-up. The severity of CB after treatment was significantly improved in the Bailing capsule group compared with the placebo group (P = 0.035), particularly in terms of expectoration (P = 0.012) and wheezing (P = 0.003). The risk of adverse events, mainly including infectious and invasive diseases and gastrointestinal symptoms, did not significantly differ between the two groups (29.6% vs. 30.4%).Conclusion: In patients with CB, Bailing capsule significantly reduces the frequency of AECB and ameliorates the severity of AECB and CB symptoms.Clinical Trail Registration:https://www.chictr.org.cn, identifer ChiCTR1900025707.

Biochar (BC) is widely utilized as a soil amendment; however, for widely distributed seasonally frozen soils, the effect of BC on soil and the optimal utilization of BC during the freeze‒thaw process are still unclear. In this study, the effects of freeze‒thaw aged biochar (FT-BC) and BC on soil properties and wheat cultivation were systematically investigated, and the underlying interaction mechanism between BC and soil was explored. The results show that FT-BC dramatically reduces the adverse effects of freeze‒thaw cycles on soil, enhances wheat growth, and increases dry matter yield by 17.5 %, which is mainly attributed to the ability of FT-BC to maintain soil structure, reduce water loss rates to below 0.20 g/h, and decrease nitrogen leaching by more than 20 % during freeze‒thaw cycles. Additionally, fresh BC had a greater effect on the fixation of cadmium than FT-BC in the soil, reducing its accumulation in wheat by 22.5 %. Multiple characterizations revealed that the freeze‒thaw process increased the porosity and specific surface area of FT-BC, providing more sites for water and nitrogen adsorption, whereas the dissolved organic matter released from fresh BC had a better ability to trap cadmium. These findings provide insights into the interactions between BC and soil components during the freeze‒thaw process and suggest the optimized utilization of fresh BC and FT-BC for different soil repair purposes.

Abstract Metal-halide perovskite thin monocrystals featuring efficient carrier collection and transport capabilities are well suited for radiation detectors, yet their growth in a generic, well-controlled manner remains challenging. Here, we reveal that mass transfer is one major limiting factor during solution growth of perovskite thin monocrystals. A general approach is developed to overcome synthetic limitation by using a high solute flux system, in which mass diffusion coefficient is improved from 1.7×10–10 to 5.4×10–10 m2 s–1 by suppressing monomer aggregation. The generality of this approach is validated by the synthesis of 29 types of perovskite thin monocrystals at 40–90 °C with the growth velocity up to 27.2 μm min–1. The as-grown perovskite monocrystals deliver a high X-ray sensitivity of 1.74×105 µC Gy−1 cm−2 without applied bias. The findings regarding limited mass transfer and high-flux crystallization are crucial towards advancing the preparation and application of perovskite thin monocrystals.

Advanced constructions in the automotive, military, and aircraft sectors often employ textile materials. This is due to its advantageous mechanical characteristics, appealing supporting components, affordable manufacture, and simple handling. For architectural layout, textile composite analysis becomes crucial. It is costly and time-consuming to experimentally determine the rigidity and durability of textile materials. Due to the impossibility of disintegration, experimental testing can only provide the characteristics of a single textile layer. The disadvantage of a textile layer made up of various fibre orientations is that it is likely to display anisotropic physical performance. Based on the physical reaction of glass and epoxy resin materials, also the design of the textile materials, a multi-parameter (MP) analysis is used to identify the substance behaviour of textile materials via virtual testing. An estimate for just one layer or a whole textile prototype may be created using these simulated trials. Pressure-dependent and nonlinear responses of materials in the multi-parameter analysis are material models created especially for this purpose and are used to simulate. The simulations are contrasted with the outcomes of experimental tests, which reveal the properties of the textile materials. The findings stated that the proposed model has provided rigidity-dislocation of 0.30 in the simulation results.

Abstract. Background:. Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized immune-mediated disorder that can affect almost any organ in the human body. IgG4-RD can be categorized into proliferative and fibrotic subtypes based on patients' clinicopathological characteristics. This study aimed to compare the clinical manifestations, laboratory findings, and treatment outcomes of IgG4-RD among different subtypes. Methods:. We prospectively enrolled 622 patients with newly diagnosed IgG4-RD at Peking Union Medical College Hospital from March 2011 to August 2021. The patients were divided into three groups according to their clinicopathological characteristics: proliferative, fibrotic, and mixed subtypes. We compared demographic features, clinical manifestations, organ involvement, laboratory tests, and treatment agents across three subtypes. We then assessed the differences in treatment outcomes among 448 patients receiving glucocorticoids alone or in combination with immunosuppressants. Moreover, risk factors of relapse were revealed by applying the univariate and multivariate Cox regression analysis. Results:. We classified the 622 patients into three groups consisting of 470 proliferative patients, 55 fibrotic patients, and 97 mixed patients, respectively. We found that gender distribution, age, disease duration, and frequency of allergy history were significantly different among subgroups. In terms of organ involvement, submandibular and lacrimal glands were frequently involved in the proliferative subtype, while retroperitoneum was the most commonly involved site in both fibrotic subtype and mixed subtype. The comparison of laboratory tests revealed that eosinophils (P = 0.010), total IgE (P = 0.006), high-sensitivity C-reactive protein (P

Carotenoids are a class of fat-soluble compounds widely associated with human health, because of their antioxidant, vision-protective and other effects. Deep eutectic solvents (DESs) are a new generation of green solvents. DESs are convenient to produce and have higher biocompatibility, biodegradability, solvent efficiency, thermal stability, and lower volatility compared to traditional organic solvents. Although DES has exhibited effective extraction on natural substances in food, its application on the extraction of carotenoids have not yet been widely studied. In this paper, the characteristics and classification of DES are described, the application of DES on extraction of carotenoids is reviewed, the existing problems for the separation of carotenoids from DES are proposed, and the application perspective of DES in the extraction and separation of carotenoids is outlined, aiming to provide a reference for the development and application of new green solvents for carotenoid extraction.

This study aimed to investigate ultrasound features of arteriovenous fistula stenosis and their relationship with primary patency after percutaneous transluminal angioplasty (post-intervention primary patency) and compare this classification with that using lesion location. Hemodialysis patients who underwent ultrasound-guided percutaneous transluminal angioplasty for arteriovenous fistula stenosis from July 2020 to December 2021 were retrospectively evaluated. Lesions (excluding inflow arteries) were categorized into five groups based on ultrasound features, and the clinical characteristics and risk factors affecting the post-intervention primary patency of the arteriovenous fistula were analyzed. Among 185 patients, 100 (54.05%), 36 (19.46%), 22 (11.89%), 11 (5.95%), and 16 (8.65%) were classified into the intima-dominant, non-intima-dominant, valve obstruction, vascular calcification, and mixed groups, respectively. The dialysis duration and arteriovenous fistula use time were the highest in the vascular calcification group at 86 (interquartile range: 49–140) and 77 (interquartile range: 49–110) months, respectively. Diabetes mellitus was most common in the intima-dominant group (42.0%). In Kaplan–Meier and univariate Cox analysis, type III lesion location (stenosis in the venous confluence site) was associated with the lower post-intervention primary patency. In the multivariate Cox analysis, percutaneous transluminal angioplasty times (the number of times patients were treated with percutaneous transluminal angioplasty for arteriovenous fistula stenosis dysfunction), vascular calcification, calcification at the lesion site requiring percutaneous transluminal angioplasty, and serum parathyroid hormone levels were independent risk factors for post-intervention primary patency. Ultrasound features showed that calcification of the arteriovenous fistula was detrimental to the post-intervention primary patency of arteriovenous fistula.

Objective: This study aims to assess the risk of neonatal susceptibility to COVID-19 among pregnant women. Methods: We conducted a retrospective cohort study involving 1089 pregnant women ≥28 weeks of gestational age, who were categorized into infected and uninfected groups. Data for all participants were collected through a comprehensive review of electronic medical records and follow-up phone calls. The primary outcome was neonatal infection with SARS-CoV-2, while secondary outcomes included delivery patterns and gestational age at delivery. Results: Maternal vaccination (OR 95%CI:0.63[0.46, 0.85]) and maternal infection with SARS-CoV-2 (OR 95%CI: 0.45[0.34, 0.60]) were found to be associated with a decreased risk of neonatal infection. The infected group exhibited a lower neonatal SARS-CoV-2 infection rate (25.93%) compared to the uninfected group (45.15%). Logistic regression analysis identified several risk factors associated with an increased risk of neonatal infection, including pregnancy BMI (OR 95%CI: 1.04[1.01, 1.08]), age at first pregnancy (OR 95%CI: 1.05[1.01, 1.10]), age at menarche (OR 95%CI: 1.13[1.02, 1.26]), and parturition (Yes vs. No) (OR 95%CI:1.4 [1.04,1.88]). Conclusion: Maternal vaccination and perinatal infection with SARS-CoV-2 play a protective role in preventing neonatal SARS-CoV-2 infection.

IntroductionGlioma, a prevalent and deadly brain tumor, is marked by significant cellular heterogeneity and metabolic alterations. However, the comprehensive cell-of-origin and metabolic landscape in high-grade (Glioblastoma Multiforme, WHO grade IV) and low-grade (Oligoastrocytoma, WHO grade II) gliomas remains elusive.MethodsIn this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas.ResultsNotably, astrocytes and oligodendrocyte progenitor cells (OPCs) exhibited the most substantial differences in both metabolic pathways and gene expression, indicative of their distinct origins. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for clinical relevance.DiscussionCrucially, the metabolic enzyme phosphodiesterase 8B (PDE8B) was found to be exclusively expressed and progressively downregulated in astrocytes and OPCs in higher-grade gliomas. This decreased expression identifies PDE8B as a metabolism-related oncogene in IDH-mutant glioma, marking its dual role as both a protective marker for glioma grading and prognosis and as a facilitator in glioma progression.

Introduction: Aristolochic acid nephropathy (AAN) is a kidney injury syndrome caused by aristolochic acids exposure. Our study used label-free quantitative proteomics to delineate renal protein profiles and identify key proteins after exposure to different doses of aristolochic acid I (AAI).Methods: Male C57BL/6 mice received AAI (1.25 mg/kg/d, 2.5 mg/kg/d, or 5 mg/kg/d) or vehicle for 5 days.Results and discussion: The results showed that AAI induced dose-dependent nephrotoxicity. Differences in renal protein profiles between the control and AAI groups increased with AAI dose. Comparing the control with the low-, medium-, and high-dose AAI groups, we found 58, 210, and 271 differentially expressed proteins, respectively. Furthermore, protein-protein interaction network analysis identified acyl-CoA synthetase medium-chain family member 3 (Acsm3), cytochrome P450 family 2 subfamily E member 1 (Cyp2e1), microsomal glutathione S-transferase 1 (Mgst1), and fetuin B (Fetub) as the key proteins. Proteomics revealed that AAI decreased Acsm3 and Cyp2e1 while increasing Mgst1 and Fetub expression in mice kidneys, which was further confirmed by Western blotting. Collectively, in AAI-induced nephrotoxicity, renal protein profiles were dysregulated and exacerbated with increasing AAI dose. Acsm3, Cyp2e1, Mgst1, and Fetub may be the potential therapeutic targets for AAN.

In order to investigate the effect of preharvest spraying of diethyl aminoethyl hexanoate (DA-6) on membrane lipid metabolism in ‘Kyoho’ grapes during postharvest storage, distilled water (control) and 50 mg/L DA-6 were used to spray grapes at the veraison stage. The grapes were harvested when they were ripe, stored at (0 ± 1) ℃ and relative humidity of 65%–70%, and evaluated for cell membrane related indicators of grape skin after 0, 20, 30, 40, 50, and 60 days. The results showed that compared with the control group, DA-6 treatment effectively inhibited the increase in the relative permeability of cell membrane during postharvest storage, maintained the activities of lipoxygense (LOX), lipase and phospolipase D (PLD), inhibited the decrease of phosphatidylcholine and phosphatidylinositol content and the increase of phosphatidyl acid content, and maintained a high relative content of unsaturated acids such as linoleic acid and linolenic acid as well as saturated fatty acids such as stearic acid, behenic acid, arachidic acid and palmitoleic acid, consequently maintaining the degree of unsaturation of fatty acids at a high level. Additionally, DA-6 treatment suppressed the expression of the LOX, Lipase, and PLD genes. In summary, preharvest spraying of 50 mg/L DA-6 can delay the senescence and prolong the storage period of ‘Kyoho’ grapes by effectively relieving the membrane lipid metabolism during storage.

AbstractContext A Chinese herbal formula, Tiaopi Xiezhuo decoction (TXD), is developed from a classical Chinese prescription Sanhuang Xiexin decoction.Objective To investigate the regulatory effect of TXD on gut dysbiosis, as a treatment of constipation in patients with peritoneal dialysis (PD).Materials and methods The chemical content of TXD was assessed by high-performance liquid chromatography. A total of 29 PD patients were enrolled and treated with TXD orally (3 g crude drug/each/twice/day) for 3 months. Blood and faecal samples were collected at the beginning and end, to determine the changes in biochemical characteristics and gut microbial composition. The stool conditions were asked to be scored. Additional 30 healthy individuals were recruited as a control for the analysis of gut microbiota.Results Although having no significant effects on serum biochemical characteristics, 3-month TXD intervention improved constipation in PD patients: decreased 80% abdominal distention (p

Hydroxyapatite (HAP) is a material renowned for its exceptional capabilities in adsorbing and exchanging heavy metal ions, making it a widely employed substance within the environmental domain. This study aims to present a novel material, namely copper–HAP (Cu–HAP), which was synthesized via an ion exchange method. The resulting material underwent comprehensive characterization using scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and Brunauer–Emmett–Teller (BET) analysis. Subsequently, based on the principle of the Fenton-like oxidation reaction, the material was used for the degradation of phenol. The outcomes of the investigation revealed that the optimal preparation conditions for the catalyst were achieved at a temperature of 40 °C, a pH value of 5, and a relative dosage of Cu–HAP at 100 mg/g. Under the reaction conditions of a catalyst dosage of 2 g/L, a 30% hydrogen peroxide concentration of 30 mM, a phenol concentration of 20 mg/L, a pH value of 6, a temperature of 40 °C, and the degradation rate of phenol impressively reached 98.12%. Furthermore, the degradation rate remained at 42.31% even after five consecutive cycles, indicating the promising potential of Cu–HAP in the treatment of recalcitrant organic compounds within this field. HIGHLIGHTS A novel copper-based catalyst (Cu–HAP) has been synthesized and utilized for the catalytic degradation of phenol.; Cu–HAP improved the efficiency of H2O2 in the traditional Fenton reaction.; Cu–HAP surface has a rich pore structure.; The phenol removal rate can still reach 42.31% after five times of reuse.;

Abstract Background Previous cohort studies have shown that exogenous sex hormone use, such as testosterone replacement therapy and oestrogen-containing contraceptives, can increase the risk of venous thromboembolism (VTE). However, the relationship between endogenous sex hormone levels and VTE remains unclear. The goal of the present study was to explore the causal roles of endogenous sex hormones, including hormone-binding globulin (SHBG), bioactive testosterone (BT), and total testosterone (TT), in VTE and its two subgroups, deep vein thrombosis (DVT) and pulmonary embolism (PE). Methods We used a genome-wide association study of sex hormones as exposure data and Finnish VTE data as the outcome. Inverse variance weighting, MR-Egger, and weighted median were used for two-sample Mendelian randomisation (MR). Sensitivity analyses included MR-Egger, MR-PRESSO, Cochrane Q test, MR Steiger, leave-one-out analysis, and funnel plot, combined with multivariate MR and replicated MR analyses using larger VTE data from the global biobank meta-analysis initiative. Linkage disequilibrium score regression (LDSC) was used to determine genetic associations and estimate sample overlap. Results Our findings genetically predicted that an increase in serum SHBG levels by one standard deviation (SD) caused 25% higher odds for VTE (OR: 1.25, 95% CI: 1.01−1.55) and 58% higher odds for PE (OR: 1.58, 95% CI: 1.20−2.08). LDSC supported the genetic correlation between these two traits and replicated analyses confirm SHBG’s genetic effect on VTE in both sexes (OR: 1.46, 95% CI: 1.20−1.78) and in females (OR: 1.49, 95% CI: 1.17−1.91). In addition, an increase in serum TT levels by one SD caused 32% higher odds for VTE (OR: 1.32, 95% CI: 1.08−1.62) and 31% higher odds for DVT (OR: 1.31, 95% CI: 1.01−1.69); however, LDSC and replicated analyses did not find a genetic correlation between TT and VTE or its subtypes. No significant correlation was observed between BT and all three outcome traits. Conclusion Our study provides evidence that elevated serum SHBG levels, as predicted by genetics, increase VTE risk. However, the causal effect of testosterone levels on VTE requires further investigation.

Abstract Coalbed methane production failures through hydraulic fracturing in the Linxing gas field in China have encountered significant setbacks, hindering efforts to enhance the recovery of deep CBM reserves in the region. To address this challenge, we investigate the potential of directional wells with multiple hydraulic slots as a stimulation technology for deep coalbed methane extraction. This study presents two numerical models to evaluate the effectiveness of this technology. The first model is a continuum damage numerical model based on the Material Point Method, which simulates large deformations and complex contact behaviors induced by hydraulic slotting in the deep coal seam. The second model is a wellbore-pore coupling model to simulate the gas extraction process. We verified both numerical models against theoretical and experimental results. We conducted a case study in the Linxing gas field using these models. The investigation assessed stress relief, gas desorption, and permeability enhancement around a large deformed hydraulic slot, as well as the gas extraction performance of a directional well with multiple slots. The results indicate that (1) The Linxing gas recovery failure may be attributed to unsuccessful hydraulic fracturing based on the history matching analysis of field production; (2) Hydraulic slotting causes gradual compaction of the slot until full closure, and results in a rapid stress drop exceeding 7 MPa in the elliptical zone surrounding the slot, which is the large plastic damage zone; (3) The enhanced permeability in plastic zone exceeds ten times the natural coal permeability, leading to total gas desorption of 556 m3 from elastic and plastic zones; (4) Performance optimization can be achieved through reducing slot length and increasing slot width when using directional well with multiple slots. In summary, this research demonstrates the efficiency of directional wells with multiple slots in enhancing gas recovery from deep coal seams.

Recombinant rabbit monoclonal antibodies (rabbit rAbs) have shown promise in various biomedical fields. However, it is challenging and costly to generate rabbit rAbs using traditional techniques. Here we describe a convenient and cost-effective method. Using this method, we generated rabbit rAbs against mouse soluble IL-6 receptor α with affinities in the range of 10-9 to 10-12 M. The presented method is suitable for industrial and academic scientists looking to customize rabbit rAbs for their research.

Shale gas reservoirs, as representative reservoirs in the Sichuan Basin, have attracted widespread attention regarding development. Using gas reservoir numerical simulation to assist development has greatly improved the work efficiency of workers. However, traditional gas reservoir numerical simulation is widely criticized for its inability to effectively integrate with geological and engineering factors. In this study, we proposed a geological engineering integration method that considers pre-fracturing parameters. We further applied it to a typical well (N03) in a certain block of the Sichuan Basin. The reliability of the method was determined through historical fitting. Based on the N03 geological model, the optimization range of fracturing construction parameters in adjacent areas was determined with the goal of maximizing EUR. Recommended values for widely distributed construction parameter combinations of Class II reservoirs were provided through orthogonal analysis. The influence order of fracturing construction parameters is (1) sand addition strength, (2) cluster spacing, (3) construction displacement, (4) fracture fluid strength, and (5) horizontal segment length. Finally, we compared the simulated data with the actual case. The results showed that an integrated numerical simulation method including geological and engineering factors can comprehensively and accurately assist in reservoir development.

Summary: Orexin is a neuropeptide released from hypothalamus regulating feeding, sleeping, arousal, and cardiovascular activity. Past research has demonstrated that orexin receptor 2 (OX2R) agonist infusion in the brain results in sympathoexcitatory responses. Here, we found that epicardial administration of OX2R agonism leads to opposite responses. We proved that OX2R is expressed mainly in DRG neurons and transported to sensory nerve endings innervating the heart. In a capsaicin-induced cardiac sympathetic afferent reflex (CSAR) model, we recorded the calcium influx in DRG neurons, measured heart rate variability, and examined the PVN c-Fos activity to prove that epicardial OX2R agonism administration could attenuate capsaicin-induced CSAR. We further showed that OX2R agonism could partially rescue acute myocardial infarction by reducing sympathetic overactivation. Our data indicate that epicardial application of OX2R agonist exerts a cardioprotective effect by attenuating CSAR. This OX2R-mediated heart-brain axis may provide therapeutic targets for acute cardiovascular diseases.

Summary: In this study, we report on mosaic variegated aneuploidy (MVA) syndrome with tetraploidy and predisposition to infertility in a family. Sequencing analysis identified that the CEP192 biallelic variants (c.1912C>T, p.His638Tyr and c.5750A>G, p.Asn1917Ser) segregated with microcephaly, short stature, limb-extremity dysplasia, and reduced testicular size, while CEP192 monoallelic variants segregated with infertility and/or reduced testicular size in the family. In 1,264 unrelated patients, variant screening for CEP192 identified a same variant (c.5750A>G, p.Asn1917Ser) and other variants significantly associated with infertility. Two lines of Cep192 mice model that are equivalent to human variants were generated. Embryos with Cep192 biallelic variants arrested at E7 because of cell apoptosis mediated by MVA/tetraploidy cell acumination. Mice with heterozygous variants replicated the predisposition to male infertility. Mouse primary embryonic fibroblasts with Cep192 biallelic variants cultured in vitro showed abnormal morphology, mitotic arresting, and disruption of spindle formation. In patient epithelial cells with biallelic variants cultured in vitro, the number of cells arrested during the prophase increased because of the failure of spindle formation. Accordingly, we present mutant CEP192, which is a link for the MVA syndrome with tetraploidy and the predisposition to male infertility.

BackgroundKlippel–Trénaunay syndrome, a kind of congenital limb-length-discrepancy disorder, is commonly associated with a variety of vascular anomalies.Case presentationWe present the case of a three-day-old newborn with a profound abdominal mass lesion during prenatal magnetic resonance imaging (MRI) examination. After delivery, physical examination revealed mild hemihypertrophy of the left lower extremity and red lesions on the left thigh. MRI of the abdomen showed a cyst-like lesion measuring 6.3 cm × 2.7 cm × 5.5 cm in the upper abdomen. Within the mass, there were also some possible calcified spots exhibiting high T1WI signals and low T2WI signals. A computed tomography (CT) scan of the abdomen was consistent with an ill-defined cystic tumor with small calcifications and encasement of mesenteric vessels. A MRI of the left lower extremity showed a tubular structure with a signal void and homogeneous strong enhancement located in the anterior subcutis of the left lower limb. The CT scan confirmed that the tubular structure was consistent with a venous malformation. This patient had features of Klippel–Trénaunay syndrome, including port-wine stains, a profound abdominal mass, and vascular malformations of the left lower extremity.ConclusionsIn this article, we presented a case of Klippel–Trénaunay syndrome, emphasizing both prenatal and confirmatory postnatal cross-sectional imaging findings. The rare presentation of an abdominal lymphatic-venous formation played a pivotal role as a crucial indicator for an early diagnosis of Klippel–Trénaunay syndrome.

Abstract Purpose The purpose of the study was to evaluate the efficacy of OLIF combined with pedicle screw internal fixation in the treatment of lumbar spinal stenosis by assessing the changes in spinal canal before and after surgery. Methods In this retrospective study, we included sixteen patients who underwent a combination of single-segment OLIF and pedicle screw internal fixation for the treatment of lumbar spinal stenosis at the Affiliated Hospital of Jiangxi University of Chinese Medicine between February 2018 and August 2022. The patients' pre- and post-operative data were compared. Intraoperative bleeding, duration of surgery, visual analogue score (VAS), Oswestry Disability Index (ODI), disc height (DH), cross-sectional area of vertebral canal (CSAVC), cross-sectional area of dural sac (CSADS), cross-sectional area of intervertebral foramen (CSAIF), spinal canal volume (SCV), spinal canal volume expansion rate, lumbar lordosis, and sagittal vertical axis were observed and recorded. The efficacy of OLIF combined with pedicle screw internal fixation for lumbar spinal stenosis on spinal canal changes before and after surgery was summarized. Results The results showed that OLIF combined with pedicle screw internal fixation effectively restored disc height and increased the cross-sectional area of the spinal canal. It also had an indirect decompression effect. The intraoperative bleeding and duration of surgery were within acceptable ranges. The VAS and ODI scores significantly improved after surgery, indicating a reduction in pain and improvement in functional disability. The CSAVC, CSADS, CSAIF, SCV, and spinal canal volume expansion rate were all increased postoperatively. Additionally, there was improvement in lumbar lordosis and sagittal vertical axis. We conducted a follow-up of all patients at 1 year after the surgery. The results revealed that the parameter values at 1 year post-surgery showed varying degrees of decrease or increase compared to the immediate postoperative values. However, these values remained statistically significant when compared to the preoperative parameter values (P

Abstract Background Plant-based dietary patterns may affect colorectal cancer (CRC) related outcomes, while risks differ in the quality of plant foods. We aimed to examine the association of plant-based diet quality with risks of CRC incidence and mortality and whether this association was modified by genetic risk. Methods This prospective cohort study included 186,675 participants free of cancer when the last dietary recall was completed. We calculated three plant-based diet indices (PDIs), i.e., the overall plant-based diet index (PDI), the healthful plant-based diet index (hPDI), and the unhealthful plant-based diet index (uPDI) representing adherence to plant-based diets with diverse quality. Genetic risk was characterized using a weighted polygenic risk score (PRS), capturing overall risk variants associated with CRC. Hazard ratios (HR) and 95% confidential intervals (CI) were estimated by the cause-specific Cox proportional hazards model. Results Over a follow-up of 9.5 years, 2163 cases and 466 deaths from CRC were documented. The HR of CRC incidence was 0.88 (95% CI, 0.81–0.96) and 0.91 (95% CI, 0.84–0.99) per 10-score increase in PDI and hPDI, respectively. Compared to the lowest quartile, PDI, hPDI, and uPDI in the highest quartile were associated with a 13% decrease, a 15% decrease, and a 14% increase in risk of incident CRC, respectively. We found a joint association of genetic risk and PDIs with incident CRC, with the highest hazard observed in those carrying higher PRS and adhering to lower-quality PDIs. The inverse association of PDI and hPDI with CRC mortality was pronounced in males. Conclusions Our results suggested that better adherence to overall and healthful plant-based diets was associated with a lower risk of CRC, whereas an unhealthful plant-based diet was associated with a higher CRC risk. Consumption of a higher-quality plant-based diet combined with decreased genetic risk conferred less susceptibility to CRC. Our findings highlighted the importance of food quality when adhering to a plant-based dietary pattern for CRC prevention in the general population.

Temperature drift is an important factor affecting the measurement accuracy of desktop NMR spectrometers, and adding a field-locking coil to the probe to achieve field-frequency interlocking is a common means of suppressing temperature drift. In this paper, a dual-channel miniaturised RF probe with an external field-locking channel is designed based on a laboratory compact Halbach magnet. The coil diameter, height, number of turns, turn spacing and enamelled wire radius were optimized based on the solenoid structure. The optimum solenoid size was obtained with an enameled wire radius of 0.4 mm, a coil diameter and height of 8.2 mm, a turn spacing of 1.6 mm and a number of turns of 5. Based on the simulation results, the detection and field-locking coils were fabricated, and tested in conjunction with the peripheral circuitry. The results show that the crosstalk between the two coils is low, the signal-to-noise ratio of the detection channel is above 50 and the signal-to-noise ratio of the locking channel is above 20. Final field locking experiments were performed and the frequency drift of the overall system after equipping the locking field was approximately 0.2 ppm/h (1 ppm=10-6), verifying that this probe design can be applied in compact Halbach magnet-based NMR analysis facilities.

Abstract Background The continuously developing pesticide resistance is a great threat to agriculture and human health. Understanding the mechanisms of insecticide resistance is a key step in dealing with the phenomenon. Insect cuticle is recently documented to delay xenobiotic penetration which breaks the previous stereotype that cuticle is useless in insecticide resistance, while the underlying mechanism remains scarce. Results Here, we find the integument contributes over 40.0% to insecticide resistance via different insecticide delivery strategies in oriental fruit fly. A negative relationship exists between cuticle thickening and insecticide penetration in resistant/susceptible, also in field strains of oriental fruit fly which is a reason for integument-mediated resistance. Our investigations uncover a regulator of insecticide penetration that miR-994 mimic treatment causes cuticle thinning and increases susceptibility to malathion, whereas miR-994 inhibitor results in opposite phenotypes. The target of miR-994 is a most abundant cuticle protein (CPCFC) in resistant/susceptible integument expression profile, which possesses capability of chitin-binding and influences the cuticle thickness-mediated insecticide penetration. Our analyses find an upstream transcriptional regulatory signal of miR-994 cascade, long noncoding RNA (lnc19419), that indirectly upregulates CPCFC in cuticle of the resistant strain by sponging miR-994. Thus, we elucidate the mechanism of cuticular competing endogenous RNAs for regulating insecticide penetration and demonstrate it also exists in field strain of oriental fruit fly. Conclusions We unveil a regulatory axis of lnc19419 ~ miR-994 ~ CPCFC on the cuticle thickness that leads to insecticide penetration resistance. These findings indicate that competing endogenous RNAs regulate insecticide resistance by modulating the cuticle thickness and provide insight into the resistance mechanism in insects.

Abstract The utilization of chelation reaction between metals and tannins is a common tanning method in leather chemistry. Herein, a novel combination tanning mechanism inspired environmentally benign catalyst (CMBT-Fe0) was synthesized by immobilizing Fe nanoparticles onto bayberry tannin (BT) grafted chitosan microfibers (CM). The obtained catalyst featured a well-defined microfibrous structure, on which Fe0 nanoparticles were highly dispersed to exhibit exceptional catalytic activity for the degradation of tetracycline (TC). The catalytic activity of CMBT-Fe0 was 1.72 times higher than that of the commercial Fe0 nanoparticles without immobilization, with 95.03% of TC degraded within 90.0 min. The CMBT-Fe0 catalysts were recycled 6 times, with the removal rate of TC maintained at 82.56%. Furthermore, a possible mechanism responsible for the catalytic removal of TC was provided by analyzing the catalytic degradation products via liquid chromatography-mass spectrometry. Therefore, our investigation successfully developed efficient catalysts to address the concerned environmental issue of antibiotic pollution. Graphical Abstract

Abstract Background Serotonin is an important signaling molecule that regulates secretory and sensory functions in the gut. Gut microbiota has been demonstrated to affect serotonin synthesis in rodent models. However, how gut microbes regulate intestinal serotonin production in piglets remains vague. To investigate the relationship between microbiota and serotonin specifically in the colon, microbial composition and serotonin concentration were analyzed in ileum-cannulated piglets subjected to antibiotic infusion from the ileum when comparing with saline infusion. Microbes that correlated positively with serotonin production were isolated from piglet colon and were further used to investigate the regulation mechanisms on serotonin production in IPEC-J2 and a putative enterochromaffin cell line RIN-14B cells. Results Antibiotic infusion increased quantities of Lactobacillus amylovorus (LA) that positively correlated with increased serotonin concentrations in the colon, while no effects observed for Limosilactobacillus reuteri (LR). To understand how microbes regulate serotonin, representative strains of LA, LR, and Streptococcus alactolyticus (SA, enriched in feces from prior observation) were selected for cell culture studies. Compared to the control group, LA, LR and SA supernatants significantly up-regulated tryptophan hydroxylase 1 (TPH1) expression and promoted serotonin production in IPEC-J2 cells, while in RIN-14B cells only LA exerted similar action. To investigate potential mechanisms mediated by microbe-derived molecules, microbial metabolites including lactate, acetate, glutamine, and γ-aminobutyric acid were selected for cell treatment based on computational and metabolite profiling in bacterial supernatant. Among these metabolites, acetate upregulated the expression of free fatty acid receptor 3 and TPH1 while downregulated indoleamine 2,3-dioxygenase 1. Similar effects were also recapitulated when treating the cells with AR420626, an agonist targeting free fatty acid receptor 3. Conclusions Overall, these results suggest that Lactobacillus amylovorus showed a positive correlation with serotonin production in the pig gut and exhibited a remarkable ability to regulate serotonin production in cell cultures. These findings provide evidence that microbial metabolites mediate the dialogue between microbes and host, which reveals a potential approach using microbial manipulation to regulate intestinal serotonin biosynthesis.

Movement and muscle control are crucial for the survival of all free-living organisms. This study aimed to explore differential patterns of cortical and subcortical activation across different stages of muscle control using functional magnetic resonance imaging (fMRI). An event-related design was employed. In each trial, participants (n = 10) were instructed to gently press a button with their right index finger, hold it naturally for several seconds, and then relax the finger. Neural activation in these temporally separated stages was analyzed using a General Linear Model. Our findings revealed that a widely distributed cortical network, including the supplementary motor area and insula, was implicated not only in the pressing stage, but also in the relaxation stage, while only parts of the network were involved in the steady holding stage. Moreover, supporting the direct/indirect pathway model of the subcortical basal ganglia, their substructures played distinct roles in different stages of muscle control. The caudate nucleus exhibited greater involvement in muscle contraction, whereas the putamen demonstrated a stronger association with muscle relaxation; both structures were implicated in the pressing stage. Furthermore, the subthalamic nucleus was exclusively engaged during the muscle relaxation stage. We conclude that even the control of simple muscle movements involves intricate automatic higher sensory–motor integration at a neural level, particularly when coordinating relative muscle movements, including both muscle contraction and muscle relaxation; the cortical and subcortical regions assume distinct yet coordinated roles across different stages of muscle control.

Abstract Background Femoral neck fracture (FNF) is a very common traumatic disorder and a major cause of blood supply disruption to the femoral head, which may lead to a severe long-term complication, osteonecrosis of femoral head (ONFH). Early prediction and evaluation of ONFH after FNF could facilitate early treatment and may prevent or reverse the development of ONFH. In this review paper, we will review all the prediction methods reported in the previous literature. Methods Studies on the prediction of ONFH after FNF were included in PubMed and MEDLINE databases with articles published before October 2022. Further screening criteria were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. This study highlights all the advantages and disadvantages of the prediction methods. Results There were a total of 36 studies included, involving 11 methods to predict ONFH after FNF. Among radiographic imaging, superselective angiography could directly visualize the blood supply of the femoral head, but it is an invasive examination. As noninvasive detection methods, dynamic enhanced magnetic resonance imaging (MRI) and SPECT/CT are easy to operate, have a high sensitivity, and increase specificity. Though still at the early stage of development in clinical studies, micro-CT is a method of highly accurate quantification that can visualize femoral head intraosseous arteries. The prediction model relates to artificial intelligence and is easy to operate, but there is no consensus on the risk factors of ONFH. For the intraoperative methods, most of them are single studies and lack clinical evidence. Conclusion After reviewing all the prediction methods, we recommend using dynamic enhanced MRI or single photon emission computed tomography/computed tomography in combination with the intraoperative observation of bleeding from the holes of proximal cannulated screws to predict ONFH after FNF. Moreover, micro-CT is a promising imaging technique in clinical practice.

Abstract Anti-PD-1 therapy has shown promising outcomes in the treatment of different types of cancer. It is of fundamental interest to analyze the efficacy of anti-PD-1 therapy in cancer patients infected with hepatitis B virus (HBV) since the comorbidity of HBV and cancer is widely documented. We designed a multicenter retrospective study to evaluate the efficacy of anti-PD-1 therapy on non-liver cancer patients infected with HBV. We found anti-PD-1 therapy achieved much better outcomes in HBV+ non-liver cancer patients than their HBV– counterparts. We performed single-cell RNA sequencing (scRNA-seq) on peripheral blood mononuclear cells (PBMCs) from esophageal squamous cell carcinoma (ESCC) patients. We found both cytotoxicity score of T cells and MHC score of B cells significantly increased after anti-PD-1 therapy in HBV+ ESCC patients. We also identified CX3CR1high TEFF, a subset of CD8+ TEFF, associated with better clinical outcome in HBV+ ESCC patients. Lastly, we found CD8+ TEFF from HBV+ ESCC patients showing higher fraction of Exhaustionhi T than their HBV– counterpart. In summary, anti-PD-1 therapy on HBV+ non-liver cancer patients is safe and achieves better outcomes than that on HBV– non-liver cancer patients, potentially because HBV+ patients had higher fraction of Exhaustionhi T, which made them more efficiently respond to anti-PD-1 therapy.

The obstructed coronary artery undergoes a series of pathological changes due to ischemic-hypoxic shocks during acute myocardial infarction (AMI). However, the altered DNA methylation levels in endothelial cells under these conditions and their implication for the etiopathology of AMI have not been investigated in detail. This study aimed to explore the relationship between DNA methylation and pathologically altered gene expression profile in human umbilical vein endothelial cells (HUVECs) subjected to oxygen-glucose deprivation (OGD), and its clinical implications in AMI patients. The Illumina Infinium MethylationEPIC BeadChip assay was used to explore the genome-wide DNA methylation profile using the Novaseq6000 platform for mRNA sequencing in 3 pairs of HUVEC-OGD and control samples. GO and KEGG pathway enrichment analyses, as well as correlation, causal inference test (CIT), and protein-protein interaction (PPI) analyses identified 22 hub genes that were validated by MethylTarget sequencing as well as qRT-PCR. ELISA was used to detect four target molecules associated with the progression of AMI. A total of 2,524 differentially expressed genes (DEGs) and 22,148 differentially methylated positions (DMPs) corresponding to 6,642 differentially methylated genes (DMGs) were screened (|Δβ|>0.1 and detection p < 0.05). After GO, KEGG, correlation, CIT, and PPI analyses, 441 genes were filtered. qRT-PCR confirmed the overexpression of VEGFA, CCL2, TSP-1, SQSTM1, BCL2L11, and TIMP3 genes, and downregulation of MYC, CD44, BDNF, GNAQ, RUNX1, ETS1, NGFR, MME, SEMA6A, GNAI1, IFIT1, and MEIS1. DNA fragments BDNF_1_ (r = 0.931, p < 0.0001) and SQSTM1_2_NEW (r = 0.758, p = 0.0043) were positively correlated with the expressions of corresponding genes, and MYC_1_ (r = −0.8245, p = 0.001) was negatively correlated. Furthermore, ELISA confirmed TNFSF10 and BDNF were elevated in the peripheral blood of AMI patients (p = 0.0284 and p = 0.0142, respectively). Combined sequencing from in vitro cellular assays with clinical samples, aiming to establish the potential causal chain of the causal factor (DNA methylation) - mediator (mRNA)—cell outcome (endothelial cell ischemic-hypoxic injury)-clinical outcome (AMI), our study identified promising OGD-specific genes, which provided a solid basis for screening fundamental diagnostic and prognostic biomarkers of coronary endothelial cell injury of AMI. Moreover, it furnished the first evidence that during ischemia and hypoxia, the expression of BNDF was regulated by DNA methylation in endothelial cells and elevated in peripheral blood.