Elastase-targeting biomimic nanoplatform for neurovascular remodeling by inhibiting NETosis mediated AlM2 inflammasome activation in ischemic stroke.

Neutrophil elastase (NE) is a protease released by activated neutrophils in the brain parenchyma after cerebral ischemia, which plays a pivotal role in the regulation of neutrophil extracellular traps (NETs) formation. The excess NETs could lead to blood-brain barrier (BBB) breakdown, overwhelming neuroinflammation, and neuronal injury. While the potential of targeting neutrophils and inhibiting NE activity to mitigate ischemic stroke (IS) pathology has been recognized, effective strategies that inhibit NETs formation remain under-explored. Herein, a biomimic multifunctional nanoplatform (HM@ST/TeTeLipos) was developed for active NE targeting and IS treatment. The core of the HM@ST/TeTeLipos consisted of sivelestat-loaded ditelluride-containing liposomes with ROS-responsive and NE-inhibiting properties. The outer shell was composed of platelet-neutrophil hybrid membrane vesicles (HMVs), which acted to hijack neutrophils and neutralize proinflammatory cytokines. Our studies revealed that HM@ST/TeTeLipos could effectively inhibit NE activity, thereby suppressing the release of NETs, impeding the activation of the AIM2 inflammasome, and consequently redirecting the immune response away from a pro-inflammatory M1 microglia phenotype. This resulted in enhanced neurovascular remodeling, reduced BBB disruption, and diminished neuroinflammation, ultimately promoting neuron survival. We believe that this innovative approach holds significant potential for improving the treatment of IS and various NE-mediated inflammatory diseases.

Functional characterization of Large yellow croaker (Larimichthys crocea) PeroxiredoxinIV (PrxIV) gene promoter.

Peroxiredoxin IV (PrxIV), which possesses an N-terminal signal peptide, is the only secretable protein in Prx family. PrxIV can protect cells against reactive oxygen species (ROS) and act as a DAMP to promote infection-independent immune response. However, the characterization and regulation of promoters of PrxIV genes are rarely reported. In this study, a 1511-bp 5'-flanking sequence of large yellow croaker (Larimichthys crocea) PrxIV (LcPrxIV) was cloned and characterized. DNA truncation combined with luciferase activity assay revealed that a fragment of -781/+20 contained in the plasmid LcPrxIV-P3 exhibited the highest promoter activity. It could initiate the luciferase expression up to 44.6-fold when compared to control plasmid pGL3-Basic. TFSEARCH analysis revealed many recognizing sequences of transcriptional factors exist within this 1511-bp sequence, including Foxo and CREB. Altogether, four putative binding sites located in three recognizing sequences of CREB were identified. Notably, co-transfection of LcPrxIV-P3 with LcCREB led to a significant 2.48-fold increase of the LcPrxIV-P3 promoter activity (P<0.01). Furthermore, the mutation at putative binding sites A, B, and all four sites of CREB in the LcPrxIV-P3 caused the significant decrease of activation on LcPrxIV-P3 promoter activity, suggesting these two sites may be the main binding sites of CREB in LcPrxIV promoter. In addition, the oxidative stress by hydrogen peroxide, rather than immune stimuli such as Poly (I: C), LPS, LTA, or PGN could cause the elevation of LcPrxIV-P3 promoter activity. When the concentration of hydrogen peroxide reached 500 µM, the promoter activity of LcPrxIV-P3 was up-regulated to 1.47-fold, which was extremely significantly different from the control (P<0.001). These results help to elucidate the regulatory mechanisms of LcPrxIV gene expression, and the role of LcPrxIV in protecting cells against oxidative stress or in oxidoreduction-dependent signal transduction.

Photovoltage-Driven Photoconductor Based on Horizontal p-n-p Junction.

The photoconductive gain theory demonstrates that the photoconductive gain is related to the ratio of carrier lifetime to carrier transit time. Theoretically, to achieve higher gain, one can either prolong the carrier lifetime or select materials with high mobility to shorten the transit time. However, the former slows the response speed of the device, while the latter increases the dark current and degrades device sensitivity. To address this challenge, a horizontal p-n-p junction-based photoconductor is proposed in this work. This device utilizes the n-region as the charge transport channel, with the charge transport direction perpendicular to the p-n-p junction. This design offers two advantages: (i) the channel is depleted by the space charge layer generated by the p and n regions, enabling the device to maintain a low dark current. (ii) The photovoltage generated in the p-n junction upon light absorption can compress the space charge layer and expand the conductive path in the n-region, enabling the device to achieve high gain and responsivity without relying on long carrier lifetimes. By adopting this device structure design, a balance between responsivity, dark current, and response speed is achieved, offering a new approach to designing high-performance photodetectors based on both traditional materials and emerging nanomaterials.

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Rhizosphere is a vital area for substance exchange and energy transfer between roots and soil microorganisms. Therefore, diazotrophs in the rhizosphere play a pivotal role in facilitating plant nitrogen acquisition. We investigated the variability in the abundance and community structure of soil diazotrophs and the influencing factors across rhizosphere soils of Cunninghamia lanceolata in three locations: Baisha State-owned Forest Farm in Longyan City (BS), Sanming Forest Ecosystem and Global Change Research Station (SM), and Wuyishan National Forest Park in Nanping City (WYS), located in the western region of Fujian Province, quantified the diazotrophic abundance by using real-time quantitative PCR, and assessed the community structure by high-throughput sequencing. The results showed that soil pH, C:N ratio, and C:(N:P) stoichiometry in SM were notably lower compared to those in BS and WYS. In SM, the abundance of the nifH gene was 6.38×108 copies·g-1, significantly lower than 1.35×109 copies·g-1 in BS and 1.10×109 copies·g-1 in WYS. Additionally, α diversity index of diazotrophs was lower in SM compared to BS and WYS, while the community structure of diazotrophs in rhizosphere soils of BS and WYS was similar, which differed significantly from that in SM. The diazotrophic sequences in the three forest farms could be divided into 5 phylum, 8 classes, 15 orders, 23 families and 33 genera, with Proteobacteria, α-proteobacteria, and Bradyrhizobium as the dominant phylotypes. Soil pH, available phosphorus, NO3--N and C:(N:P) ratio were identified as significant factors influencing both the abundance and community structure of nifH genes, with soil pH performing the greatest. Taken together, there were spatial variations in the distribution of diazotrophic abundance and community structure in C. lanceolata rhizosphere soils, with soil pH as the primary driving factor.

Biochemical Characterization of Hyaluronate Lyase CpHly8 from an Intestinal Microorganism Clostridium perfringens G1121.

Hyaluronic acid (HA) is an important component of extracellular matrices (ECM) and a linear polysaccharide involved in various physiological and pathological processes within the biological system. Several pathogens exploit HA degradation within the extracellular matrix to facilitate infection. While many intestinal microorganisms play significant roles in HA utilization in the human body, there remains a scarcity of related studies. This paper addressed this gap by screening intestinal microorganisms capable of degrading HA, resulting in the isolation of Clostridium perfringens G1121, which had been demonstrated the ability to degrade HA. Subsequent genome sequencing and analysis of C. perfringens G1121 revealed its utilization of the polysaccharide utilization loci of HA (PULHA), which was obtained by horizontal gene transfer. The PULHA contains a sequence encoding a hyaluronic acid-specific degradation enzyme designated CpHly8, belonging to polysaccharide lyase family 8. The specific activity of CpHly8 towards HA was 142.98 U/mg, with the optimum reaction temperature and pH observed at 50℃ and 6.0, respectively. The final product of HA degradation by CpHly8 was unsaturated hyaluronic acid disaccharide. Moreover, subcutaneous diffusion experiments with trypan blue in mice revealed that CpHly8 effectively promoted subcutaneous diffusion and sustained its effects long-term, suggesting its potential application as an adjunct in drug delivery. Overall, our study enriches our understanding of intestinal microbial degradation of HA, provides new evidence for horizontal gene transfer among intestinal microorganisms, and confirms that CpHly8 is a promising candidate for intestinal microbial hyaluronidase.

Investigating the Impact of Moisture Levels on Structural Alterations and Physicochemical Properties of Cassava Flour through Extrusion: A Comprehensive Study.

The extrusion process, a vital technique for starch modification, is notably influenced by the moisture content (MC). This study aimed to elucidate the effect of varying MC levels (18, 22, 26, and 30%) on the structural and physicochemical characteristics of cassava flour during extrusion. Extrusion resulted in the fraction of degree of polymerization 13‒24, degree of branching, and molecular weight increased with increasing MC, with values of above indexes being 32.29%, 1.05%, and 1.21 × 105 g/mol, respectively, at a MC of 18%. This suggested that the degradation of amylopectin and amylose. Additionally, there was an increase in rapidly digestible starch (RDS) and a decrease in slowly digestible starch (SDS) in the extrudates in comparison to the native cassava flour. The extrusion of cassava flour at 18% MC exhibited the highest levels of RDS and SDS, reaching 64.52% and 4.06%, respectively. These findings indicated that low moisture extrusion could be a more effective method for disrupting the structure of cassava starch and enhancing the digestibility of cassava flour, offering valuable insights for the optimized use of cassava extrudates in various applications.

Occupational Exposure to Silica Dust and Silicosis Risk in Chinese Noncoal Mines: Qualitative and Quantitative Risk Assessment.

BACKGROUND: Despite increasing awareness, silica dust-induced silicosis still contributes to the huge disease burden in China. Worryingly, recent silica dust exposure levels and silicosis risk in Chinese noncoal mines remain unclear. OBJECTIVE: We aimed to determine recent silica dust exposure levels and assess the risk of silicosis in Chinese noncoal mines. METHODS: Between May and December 2020, we conducted a retrospective cohort study on 3 noncoal mines and 1 public hospital to establish, using multivariable Cox regression analyses, prediction formulas of the silicosis cumulative hazard ratio (H) and incidence (I) and a cross-sectional study on 155 noncoal mines in 10 Chinese provinces to determine the prevalence of silica dust exposure (PDE), free silica content, and total dust and respirable dust concentrations. The qualitative risk of silicosis was assessed using the International Mining and Metals Commission's risk-rating table and the occupational hazard risk index; the quantitative risk was assessed using prediction formulas. RESULTS: Kaplan-Meier survival analysis revealed significant differences in the silicosis probability between silica dust-exposed male and female miners (log-rank test χ21=7.52, P=.01). A total of 126 noncoal mines, with 29,835 miners and 4623 dust samples, were included; 13,037 (43.7%) miners were exposed to silica dust, of which 12,952 (99.3%) were male. The median PDE, free silica content, total dust concentration, and respirable dust concentration were 61.6%, 27.6%, 1.30 mg/m3, and 0.58 mg/m3, respectively, indicating that miners in nonmetal, nonferrous metal, small, and open-pit mines suffer high-level exposure to silica dust. Comprehensive qualitative risk assessment showed noncoal miners had a medium risk of silicosis, and the risks caused by total silica dust and respirable silica dust exposure were high and medium, respectively. When predicting H and I over the next 10, 20, and 30 years, we assumed that the miner gender was male. Under exposure to current total silica dust concentrations, median I10, I20, and I30 would be 6.8%, 25.1%, and 49.9%, respectively. Under exposure to current respirable silica dust concentrations, median I10, I20, and I30 would be 6.8%, 27.7%, and 57.4%, respectively. These findings showed that miners in nonmetal, nonferrous metal, small, and open-pit mines have a higher I and higher qualitative silicosis risk. CONCLUSIONS: Chinese noncoal miners, especially those in nonmetal, nonferrous metal, small, and open-pit mines, still suffer high-level exposure to silica dust and a medium-level risk of silicosis. Data of both total silica dust and respirable silica dust are vital for occupational health risk assessment in order to devise effective control measures to reduce noncoal mine silica dust levels, improve miners' working environment, and reduce the risk of silicosis.

Induced pluripotent stem cell-derived mesenchymal stem cells enhance acellular nerve allografts to promote peripheral nerve regeneration by facilitating angiogenesis.

Previous research has demonstrated the feasibility of repairing nerve defects through acellular allogeneic nerve grafting with bone marrow mesenchymal stem cells. However, adult tissue-derived mesenchymal stem cells encounter various obstacles, including limited tissue sources, invasive acquisition methods, cellular heterogeneity, purification challenges, cellular senescence, and diminished pluripotency and proliferation over successive passages. In this study, we used induced pluripotent stem cell-derived mesenchymal stem cells, known for their self-renewal capacity, multilineage differentiation potential, and immunomodulatory characteristics. We used induced pluripotent stem cell-derived mesenchymal stem cells in conjunction with acellular nerve allografts to address a 10 mm-long defect in a rat model of sciatic nerve injury. Our findings reveal that induced pluripotent stem cell-derived mesenchymal stem cells exhibit survival for up to 17 days in a rat model of peripheral nerve injury with acellular nerve allograft transplantation. Furthermore, the combination of acellular nerve allograft and induced pluripotent stem cell-derived mesenchymal stem cells significantly accelerates the regeneration of injured axons and improves behavioral function recovery in rats. Additionally, our in vivo and in vitro experiments indicate that induced pluripotent stem cell-derived mesenchymal stem cells play a pivotal role in promoting neovascularization. Collectively, our results suggest the potential of acellular nerve allografts with induced pluripotent stem cell-derived mesenchymal stem cells to augment nerve regeneration in rats, offering promising therapeutic strategies for clinical translation.

Keggin structure heteropolyacid-catalyzed phosphinylation of secondary propargyl alcohols with phosphine oxides to γ-ketophosphine oxides.

Phosphotungstic acid with a Keggin structure as an efficient, simple and green catalyst for the phosphinylation of secondary propargyl alcohols with phosphine oxides to afford γ-ketophosphine oxides with up to 88% isolated yield was developed using dimethyl carbonate as a green solvent. Diaryl- or alkylaryl-substituted propargyl alcohols, and diaryl or arylalkylphosphine oxides could tolerate the system, which reduced the catalyst dosage, and avoided the use of multi-components and toxic solvents. More interestingly, phosphotungstic acid exhibited the best activity when 0.58 moles of water were added per mole of HPWA, elevating the yield from 55% to 85%. An 18O labelled product was afforded using trace H218O instead of H2O, indicating the participation of water in the reaction. Besides, our work underscores the importance and effect of a small amount of water, acting to promote the transformation of secondary propargyl alcohols into enones, which should be the real intermediates of the reaction. A mechanism involving a carbocation, Meyer-Schuster rearrangement and Michael addition of enones was proposed.

Characterization of a triple-type chimeric vaccine against human papillomavirus types 18, 45, and 59.

Persistent infection with high-risk human papillomavirus (HPV) types can lead to the development of cancer in HPV-infected tissues, including the cervix, oropharynx, anus, penis, vagina, and vulva. While current HPV vaccines cover approximately 90 % of cervical cancers, nearly 10 % of cases associated with HPV types not included in the vaccines remain unaddressed, notably HPV59. This study describes the development of a chimeric virus-like particle (VLP) targeting HPV18/45/59, proposed as a vaccine candidate for high-risk HPV type (HPV59) currently lacking commercial vaccines. Given that the majority of neutralizing antibody epitopes are located on the surface loops, we engineered a strategic swap of these loops between the closely related HPV18 and HPV45. This methodology was then extended to incorporate surface loops of HPV59, resulting in the lead candidate construct of the H18-45BCEF-59HI chimeric VLP with two surface loops swapping from HPV45 to HPV18. Characterization confirmed that H18-45BCEF-59HI closely resembled the wild-type (WT) backbone types in particle size and morphology, as verified by Transmission Electron Microscopy (TEM), High-Performance Size-Exclusion Chromatography (HPSEC), and Analytical Ultracentrifugation (AUC), and demonstrated similar thermal stability as evidenced by Differential Scanning Calorimetry (DSC). Immunization studies in mice with the chimeric VLPs assessed their immunogenicity, revealing that the H18-45EF-59HI chimeric VLP exhibited optimal cross-neutralization. Additionally, when produced in a Good Manufacturing Practice (GMP)-like facility, the H18-45BCEF-59HI VLP was selected as a promising vaccine candidate for the prevention of HPV18/45/59 infection. This study not only offers a potential solution to the current vaccination gap but also provides a foundational approach for the design of vaccines targeting viruses with multiple subtypes or variants.

Phylogenetic and Genetic Variation Analysis of Porcine Epidemic Diarrhea Virus in East Central China during 2020-2023.

Porcine epidemic diarrhea virus (PEDV) is a major causative pathogen of a highly contagious, acute enteric viral disease. This study evaluated the emergence of nine variants in Jiangsu and Anhui provinces of China from 2020 to 2023. S gene-based phylogenetic analysis indicated that three variants belong to the G1c subgroup, while the other six strains are clustered within the G2c subgroup. Recombination analyses supported that three variants of the G1c subgroup were likely derived from recombination of parental variants FR0012014 and a donor variant AJ1102. In addition, there are novel mutations on amino acid 141-148 and these likely resulted in changes in antigenicity in the three variants. These results illustrated that the study provides novel insights into the epidemiology, evolution, and transmission of PEDV in China.

A multifunctional scaffold that promotes the scaffold-tissue interface integration and rescues the ROS microenvironment for repair of annulus fibrosus defects.

Due to the limited self-repair ability of the annulus fibrosus (AF), current tissue engineering strategies tend to use structurally biomimetic scaffolds for AF defect repair. However, the poor integration between implanted scaffolds and tissue severely affects their therapeutic effects. To solve this issue, we prepared a multifunctional scaffold containing loaded lysyl oxidase (LOX) plasmid DNA exosomes and manganese dioxide nanoparticles (MnO2 NPs). LOX facilitates extracellular matrix (ECM) cross-linking, while MnO2 NPs inhibit excessive reactive oxygen species (ROS)-induced ECM degradation at the injury site, enhancing the crosslinking effect of LOX. Our results revealed that this multifunctional scaffold significantly facilitated the integration between the scaffold and AF tissue. Cells were able to migrate into the scaffold, indicating that the scaffold was not encapsulated as a foreign body by fibrous tissue. The functional scaffold was closely integrated with the tissue, effectively enhancing the mechanical properties, and preventing vascular invasion, which emphasized the importance of scaffold-tissue integration in AF repair.

Novel Susceptibility Genes and Biomarkers for Obstructive Sleep Apnea: Insights from Genetic and Inflammatory Proteins.

STUDY OBJECTIVES: Numerous observational studies link obstructive sleep apnea (OSA) to inflammatory proteins, yet the directionality of these associations remains ambiguous. Therefore, we aimed to clarify the potential associations of gene-predicted inflammatory proteins with OSA. METHODS: Based on genome-wide association study data, we applied Mendelian randomization (MR) to explore potential connections between circulating inflammatory proteins and OSA, primarily using the inverse variance weighting method for robustness. Cochran's Q test, MR‒Egger intercept test, MR-PRESSO, and leave-one-out method were used to perform sensitivity tests for pleiotropy and heterogeneity. Replication analyses and meta-analyses were performed using other independent data. Steiger tests and multivariate MR assessed the independent effects of exposure factors, and the functional mapping and annotation (FUMA) platform was used to identify key genes to enhance the understanding of genetics. RESULTS: Our investigation revealed 21 circulating inflammatory proteins significantly associated with OSA-related phenotypes. Notably, IL-10RA, IL-18R1, TNFSF14, CCL23, ADA, and SLAMF1 had significant effects on multiple phenotypes. After FDR correction, IL-18R1, SLAMF1, IL-10RA, and IL-17C were identified as important candidates for OSA, and multivariate MR analysis strengthened the independent heritability of 20 inflammatory factors. The FUMA platform revealed seven overlapping genes: ROBO1, PRIM1, NACA, SHBG, HSD17B6, RBMS2, and WWOX. All reverse MR analyses and sensitivity analyses confirmed the robustness of these associations. CONCLUSIONS: Our results underscore crucial associations between inflammatory proteins and OSA pathogenesis, revealing new correlates and susceptibility genes. These findings advance biomarker identification for OSA risk and highlight the importance of genetic and inflammatory profiles in OSA management.

Identification and validation of inflammatory subtypes in intrahepatic cholangiocellular carcinoma.

BACKGROUND: Inflammation plays a critical role in tumor development. Inflammatory cell infiltration and inflammatory mediator synthesis cause changes in the tumor microenvironment (TME) in several cancers, especially in intrahepatic cholangiocellular carcinoma (ICC). However, methods to ascertain the inflammatory state of patients using reliable biomarkers are still being explored. METHOD: We retrieved the RNA sequencing and somatic mutation analyses results and the clinical characteristics of 244 patients with ICC from published studies. We performed consensus clustering to identify the molecular subtypes associated with inflammation. We compared the prognostic patterns, clinical characteristics, somatic mutation profiles, and immune cell infiltration patterns across inflammatory subtypes. We performed quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC) to confirm gene expression. We performed logistic regression analyses to construct a nomogram predicting the inflammatory status of patients with ICC. RESULTS: Our results confirmed that ICC can be categorized into an inflammation-high subtype (IHS) and an inflammation-low subtype (ILS). Patients from each group had distinct prognosis, clinical characteristics, and TME composition. Patients with ICC in the IHS group showed poorer prognosis owing to the immunosuppressive microenvironment and high frequency of KRAS and TP53 mutations. Cancer-associated fibroblast (CAF)-derived COLEC11 reduced myeloid inflammatory cell infiltration and attenuated inflammatory responses. The results of qRT-PCR and IHC experiments confirmed that COLEC11 expression levels were significantly reduced in tumor tissues compared to those in paracancerous tissues. Patients with ICC in the IHS group were more likely to respond to treatment with immune checkpoint inhibitors (ICIs) owing to their higher tumor mutational burden (TMB) scores, tumor neoantigen burden (TNB) scores, neoantigen counts, and immune checkpoint expression levels. Finally, we developed a nomogram to effectively predict the inflammatory status of patients with ICC based on their clinical characteristics and inflammatory gene expression levels. We evaluated the calibration, discrimination potential, and clinical utility of the nomogram. CONCLUSION: The inflammatory response in IHS is primarily induced by myeloid cells. COLEC11 can reduce the infiltration level of this group of cells, and myeloid inflammatory cells may be a novel target for ICC treatment. We developed a novel nomogram that could effectively predict the inflammatory state of patients with ICC, which will be useful for guiding individualized treatment plans.

Incorporating whole soybean pulp into wheat flour for nutrient-enriched steamed bread: Exploring the impact on physical and nutritional characteristics.

This research explored the impact of incorporating various levels of whole soybean pulp (WSP) (10%, 20%, 30%, 40%, and 50%) into wheat flour on the physical and nutritional qualities of steamed bread. In comparison with the traditional steamed bread, the substitution of up to 20% WSP did not significantly alter the specific volume, hardness, and chewiness of the steamed bread. Additionally, the crumb texture of the steamed bread with 20% WSP maintained small and uniform pores, with optimal springiness and cohesiveness. Nutritionally, the substitution of 10%-50% WSP enhanced total dietary fiber, total phenolics, and protein by 9.40%-89.79%, 14.96%-116.31%, and 3.45%-34.36%, respectively. Isoflavones in the steamed bread increased markedly from 22.92 µg/g to a range of 140.12-997.12 µg/g. The expected glycemic index showed a decrease from 90.24 to between 85.85 and 70.75, whereas amino acid scores improved from 59.22 to a range of 64.58-65.08, with lysine (Lys) scores notably increasing from 59.22 to between 64.96 and 88.80. In conclusion, partially replacing wheat flour with WSP is an effective method for enhancing the nutritional profile and addressing the essential amino acid imbalance in steamed bread. PRACTICAL APPLICATION: This study partially replaced flour with WSP to improve the steamed bread's nutritional quality. The optimal substitution level was determined to be 20% WSP, which improves the bread's nutritional value without significantly impacting its physical qualities. Furthermore, WSP is produced from soaked soybeans through hot water milling. This process simplifies soybean processing, lowers energy consumption and costs, and reduces pollution. It also effectively retains essential nutrients, such as protein, dietary fiber, polyphenols, and soy isoflavones, ensuring the full utilization of soybeans.

Crucial time of emergency monitoring for reliable numerical pollution source identification.

The Pollution source identification (PSI) is an important issue on river water quality management especially for urban receiving water. Numerical inversion method is theoretically an effective PSI technique, which employs monitored downstream pollutant breakthrough curves to identify the pollution source. In practice, it is important to know how much monitoring data should be accumulated to provide PSI results with acceptable accuracy and uncertainty. However, no literature reports on this key point and it seriously handers the numerical PSI technology to mature practical applications. To seek a monitoring guideline for PSI, we conducted extensively numerical experiments for single-point source instantaneous release taking Bayesian-MCMC method as the baseline inversion technique. The crucial time (Tc) phenomenon was found during the data accumulation process for Bayesian source inversion. After Tc, estimated source parameters subsequent sustained low error levels and uncertainty convergence. Results shown the presence of Tc impacted by the number and location of monitoring sections, while monitoring frequency and data error do not. Under different river hydrodynamic conditions, relative crucial time (Λ) is determined by the river's Peclet number, and minimum effective Λ was controlled by dispersion coefficient (Dx). Analytic spatial structure of Λ(U, Dx) was uncovered and this relationship successfully explained by the information entropy theory. Based on these findings, a novel design method of PSI emergency monitoring network for preparedness plan and a practical framework of PSI for emergency response were established. These findings fill the important knowledge gap in PSI applications and the guidelines provide valuable references for river water quality management.

Causal Effects of Oxidative Stress on Diabetes Mellitus and Microvascular Complications: Insights Integrating Genome-Wide Mendelian Randomization, DNA Methylation, and Proteome.

BACKGROUND: Oxidative stress (OS) is involved in the development of diabetes, but the genetic mechanisms are not completely understood. We integrated multi-omics data in order to explore the genetic relations between OS-related genes, diabetes mellitus, and microvascular complications using Mendelian randomization and colocalization analysis. METHODS: Summary-level data related to OS were acquired from respective studies of methylation, expression, and protein abundance quantitative trait loci. Genetic associations concerning diabetes, diabetic nephropathy (DN), and diabetic retinopathy (DR) were derived from the FinnGen study. Summary-data-based Mendelian randomization (SMR) analysis was conducted to evaluate the correlations between molecular features concerned with OS-related genes and diabetes mellitus, along with its microvascular complications. Additionally, we performed colocalization analysis to determine if the detected signal pairs shared a causal genetic variant. RESULTS: At the genetic level, we identified ten potential causal associations of oxidative stress genes with diabetes, along with microvascular complications, through SMR and colocalization analysis. After integrating the DNA methylation quantitative trait loci (mQTL) and expression QTL (eQTL) data, our analyses revealed a correlation between the methylation site cg26343298 and reduced expression of TP53INP1, supporting the protective role of cg26343298 methylation on type 2 diabetes (T2D) and diabetic nephropathy. Similarly, an inverse association was observed between gene methylation and expression in CHEK1 (cg07110182), confirming the beneficial effect of modification of CHEK1 by cg07110182 in diabetic retinopathy. In addition, upregulation of SUOX expression by cg22580629 was linked to a reduced risk of diabetic retinopathy. At circulating protein levels, genetically predicted a higher level of ICAM1 (OR 1.05, 95%CI 1.03-1.08) was positively connected with the risk of diabetic retinopathy. CONCLUSIONS: This SMR study elucidated that the TP53INP1 gene was putatively associated with T2D and DN risk, while the SUOX and CHEK1 genes were associated with DR risk through oxidative stress mechanisms. Additionally, our study showed a positive correlation between the ICAM-1 protein and DR. These findings may enhance our understanding of their pathogenesis and suggest new therapeutic targets for clinical practice.

Small-size temperature/high-pressure integrated sensor via flip-chip method.

Hydraulic technology with smaller sizes and higher reliability trends, including fault prediction and intelligent control, requires high-performance temperature and pressure-integrated sensors. Current designs rely on planar wafer- or chip-level integration, which is limited by pressure range, chip size, and low reliability. We propose a small-size temperature/high-pressure integrated sensor via the flip-chip technique. The pressure and temperature units are arranged vertically, and the sensing signals of the two units are integrated into one plane through silicon vias and gold-gold bonding, reducing the lateral size and improving the efficiency of signal transmission. The flip-chip technique ensures a reliable electrical connection. A square diaphragm with rounded corners is designed and optimised with simulation to sense high pressure based on the piezoresistive effect. The temperature sensing unit with a thin-film platinum resistor measures temperature and provides back-end high-precision compensation, which will improve the precision of the pressure unit. The integrated chip is fabricated by MEMS technology and packaged to fabricate the extremely small integrated sensor. The integrated sensor is characterised, and the pressure sensor exhibits a sensitivity and sensitivity drift of 7.97 mV/MPa and -0.19% FS in the range of 0-20 MPa and -40 to 120 °C. The linearity, hysteresis, repeatability, accuracy, basic error, and zero-time drift are 0.16% FS, 0.04% FS, 0.06% FS, 0.18% FS, ±0.23% FS and 0.04% FS, respectively. The measurement error of the temperature sensor and temperature coefficient of resistance is less than ±1 °C and 3142.997 ppm/°C, respectively. The integrated sensor has broad applicability in fault diagnosis and safety monitoring of high-end equipment such as automobile detection, industrial equipment, and oil drilling platforms.

Research progress on the application of organoids in gynecological tumors.

Organoids are in vitro 3D models that maintain their own tissue structure and function. They largely overcome the limitations of traditional tumor models and have become a powerful research tool in the field of oncology in recent years. Gynecological malignancies are major diseases that seriously threaten the life and health of women and urgently require the establishment of models with a high degree of similarity to human tumors for clinical studies to formulate individualized treatments. Currently, organoids are widely studied in exploring the mechanisms of gynecological tumor development as a means of drug screening and individualized medicine. Ovarian, endometrial, and cervical cancers as common gynecological malignancies have high morbidity and mortality rates among other gynecological tumors. Therefore, this study reviews the application of modelling, drug efficacy assessment, and drug response prediction for ovarian, endometrial, and cervical cancers, thereby clarifying the mechanisms of tumorigenesis and development, and providing precise treatment options for gynecological oncology patients.