Iron plaque formation and its influences on the properties of polyethylene plastic surfaces in coastal wetlands: Abiotic factors and bacterial community.

Iron (Fe) plaques in coastal wetlands are widely recognized because of their strong adsorption affinity for natural particles, but their interaction behaviors and mechanisms with plastics remain unknown. Through laboratory incubation experiments, paired with multiple characterization methods and microbial analysis, this work focused on the characteristics of Fe plaques on low-density polyethylene plastic surfaces and their relationship with environmental factors in coastal wetlands (Mangrove and Spartina alterniflora soil). The results showed that iron plaques increased the adhesive force of the plastic surface from 65.25 to 300 nN and promoted the oxidation of the plastic surface. Fe plaque formation was stimulated by salinity, anaerobic conditions, natural organic matter, and a weak alkaline scenario (pH 8.0-8.3). The Fe content showed a stable positive correlation with heavy metals loading (i.e., As, Mn, Co, Cr, Pb, and Zn). Furthermore, we revealed that Fe plaque was positively regulated by Nitrospirae through 16S rRNA high-throughput sequencing analysis. Meanwhile, Verrucomicrobia and Kiritimatiellaeota. may act as depressants by consuming salt. This work illustrated that iron plaques could enhance the role of plastics in contaminant migration by altering their adsorption performance, providing new insights into plastic interface behavior and potential ecological effects in coastal wetlands.

Plasma-catalyzed combined dynamic wave scrubbing: A novel method for highly efficient removal of multiple pollutants from flue gas at low temperatures.

In this study, we developed a novel approach combining a non-thermal plasma system with M(Ce, Cu)-Mn/13X oxidation and post-dynamic wave wet scrubbing technologies, for effectively removing multiple pollutants from flue gases. Experimental results demonstrated that the plasma coupled with post-dynamic wave wet scrubbing achieved impressive synergistic removal efficiencies of 98% for SO2, 50.9% for NO, and 51.3% for Hg0 in flue gas. Through the use of M(Ce, Cu)-Mn/13X catalysts synthesized via the co-precipitation, the oxidation efficiency of the system is significantly enhanced, with synergistic removal efficiencies reaching up to 100% for SO2, 98.7% for NO, and 96% for Hg0. Notably, (Ce-Mn)/13X exhibited superior catalytic activity, the results are supported by comprehensive sample characterization, DFT mechanistic analysis, and experimental validation. Additionally, we elucidated the plasma oxidation mechanism and the working principles of the M(Ce, Cu)-Mn/13X loaded catalysts. This innovative technology not only facilitates pollutant oxidation but also ensures their complete removal from flue gas, providing a high-efficiency, cost-effective, and environmentally friendly solution for the treatment of multi-pollutants in flue gases.

The effect of different posterior inclinations of tibial component on tibiofemoral contact pressures after unicompartmental knee arthroplasty.

BACKGROUND: Different posterior inclinations of tibial component after unicompartmental knee arthroplasty (UKA) may lead to different biomechanical characteristics of the knee joint. This finite element study was designed to investigate the tibiofemoral contact pressures after UKA with different posterior inclinations of tibial component. METHODS: Finite element model of a healthy knee joint was constructed, and mobile-bearing (MB) UKA models with 5 different posterior inclinations (3°, 5°, 7°, 9° and 11°) of tibial components were simulated. The maximum contact pressures of tibial plateau cartilage in the lateral compartment and polyethylene insert in the medial compartment were calculated based on the ground reaction force and the angle of the knee flexion obtained by 3D motion capture system. RESULTS: The loading ratio of medial and lateral compartments during standing stance (medial 54.49%, lateral 45.51%) and tibial anterior displacement (134 N, 3.89 mm) of healthy knee was basically consistent with previous experimental data. The maximum contact pressures of the medial meniscus and lateral tibial plateau cartilage of the healthy knee during standing stance were 2.14 MPa and 1.57 MPa, respectively. At the static standing phase, the maximum contact pressures of the polyethylene insert decreased from 17.90 to 17.29 Mpa, and the maximum contact pressures of the tibial plateau cartilage in the lateral compartment increased from 0.81 to 0.92 Mpa following an increase in the posterior inclination of the tibial component. At the first peak of ground reaction force, the maximum contact pressures of polyethylene insert increased from 22.37 to 25.16 MPa, and the maximum contact pressures of tibial plateau cartilage in the lateral compartment increased from 3.03 to 3.33 MPa, with the increase in the posterior inclination of the tibial component. At the second peak of ground reaction force, the maximum contact pressures of polyethylene insert decreased from 2.34 to 2.22 MPa with the increase in posterior inclination of tibial component. CONCLUSION: The preoperative and postoperative finite element models of MB UKA were well established. The results showed that the maximum contact pressures of the polyethylene insert did not change significantly with the increase in the posterior inclination of the tibial prosthesis, while the maximum contact pressures of the tibial plateau cartilage of the lateral compartment increased when the posterior inclination of the tibial prosthesis was > 7°. Our results also show that the maximum contact pressures were greater with an excessive inclination angle (11°) of the tibial component, and the pressures of the tibial plateau cartilage in the lateral compartment were more concentrated on the posterior area. This study, therefore, proposes that excessive osteotomy should be avoided.

Exploring acupuncture treatment strategies for snoring based on meridian theory. / 基于经络学说探析鼾症的针刺治疗思路.

Starting from the perspective of meridian theory, this article briefly analyzes the meridian pathophysiology of snoring and the relationship between snoring and meridian theory. It proposes that acupuncture treatment for snoring should focus on regulating qi from the shaoyang meridians, harmonizing the spirit by the governor vessel, resolving phlegm through the three yang meridians, and harmonizing qi and blood from the yangming meridians. Additionally, attention is placed on both the root cause and the symptoms, the theory of "four seas". The ultimate goal is to promote the flow of meridian and qi-blood, improve symptoms such as nighttime snoring, poor sleep quality, and daytime sleepiness, and achieve the desired outcome of stopping snoring and ensuring restful sleep.

Hierarchical cumulative network for unsupervised medical image registration.

Unsupervised deep learning techniques have gained increasing popularity in deformable medical image registration However, existing methods usually overlook the optimal similarity position between moving and fixed images To tackle this issue, we propose a novel hierarchical cumulative network (HCN), which explicitly considers the optimal similarity position with an effective Bidirectional Asymmetric Registration Module (BARM). The BARM simultaneously learns two asymmetric displacement vector fields (DVFs) to optimally warp both moving images and fixed images to their optimal similar shape along the geodesic path. Furthermore, we incorporate the BARM into a Laplacian pyramid network with hierarchical recursion, in which the moving image at the lowest level of the pyramid is warped successively for aligning to the fixed image at the lowest level of the pyramid to capture multiple DVFs. We then accumulate these DVFs and up-sample them to warp the moving images at higher levels of the pyramid to align to the fixed image of the top level. The entire system is end-to-end and jointly trained in an unsupervised manner. Extensive experiments were conducted on two public 3D Brain MRI datasets to demonstrate that our HCN outperforms both the traditional and state-of-the-art registration methods. To further evaluate the performance of our HCN, we tested it on the validation set of the MICCAI Learn2Reg 2021 challenge. Additionally, a cross-dataset evaluation was conducted to assess the generalization of our HCN. Experimental results showed that our HCN is an effective deformable registration method and achieves excellent generalization performance.

Whole-brain in vivo base editing reverses behavioral changes in Mef2c-mutant mice.

Whole-brain genome editing to correct single-base mutations and reduce or reverse behavioral changes in animal models of autism spectrum disorder (ASD) has not yet been achieved. We developed an apolipoprotein B messenger RNA-editing enzyme, catalytic polypeptide-embedded cytosine base editor (AeCBE) system for converting C·G to T·A base pairs. We demonstrate its effectiveness by targeting AeCBE to an ASD-associated mutation of the MEF2C gene (c.104T>C, p.L35P) in vivo in mice. We first constructed Mef2cL35P heterozygous mice. Male heterozygous mice exhibited hyperactivity, repetitive behavior and social abnormalities. We then programmed AeCBE to edit the mutated C·G base pairs of Mef2c in the mouse brain through the intravenous injection of blood-brain barrier-crossing adeno-associated virus. This treatment successfully restored Mef2c protein levels in several brain regions and reversed the behavioral abnormalities in Mef2c-mutant mice. Our work presents an in vivo base-editing paradigm that could potentially correct single-base genetic mutations in the brain.

In Situ Synthesis of Ru/TiO2- x @TiCN Ternary Heterojunctions for Enhanced Sonodynamic and Nanocatalytic Cancer Therapy.

Albeit nanozymes-based tumor catalytic therapy (NCT) relies on endogenous chemical reactions that could achieve tumor microenvironment (TME)-specialized reactive oxygen species (ROS) production, the unsatisfactory catalytic activity of nanozymes accompanied by complex TME poses a barrier to the therapeutic effect of NCT. Herein, a one-step in situ synthesis strategy is reported to construct ternary Ru/TiO2- x @TiCN heterojunctions through oxidative conversion of TiCN nanosheets (NSs) to TiO2- x NSs and reductive deposition of Ru3+ to Ru nanoparticles. The narrow bandgap and existence of heterojunctions enhance the ultrasound-activated ROS generation of Ru/TiO2- x @TiCN because of the accelerated electron transfer and inhibits electron-hole pair recombination. The augmented ROS production efficiency is achieved by Ru/TiO2- x @TiCN with triple enzyme-like activities, which amplifies the ROS levels in a cascade manner through the catalytic decomposition of endogenous H2 O2 to relieve hypoxia and heterojunction-mediated NCT, as well as depletion of overexpressed glutathione. The satisfactory therapeutic effects of Ru/TiO2- x @TiCN heterojunctions are achieved through synergetic sonodynamic therapy and NCT, which achieve the complete elimination of tumors without recurrence. This strategy highlights the potential of in situ synthesis of semiconductor heterojunctions as enhanced sonosensitizers and nanozymes for efficient tumor therapy.

Exploring the potential mechanism of Heng-Gu-Gu-Shang-Yu-He-Ji therapy for osteoporosis based on network pharmacology and transcriptomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Heng-Gu-Gu-Shang-Yu-He-Ji (Osteoking, OK) is a well-known formula for fracture therapy. In clinic, OK is effective in treating fractures while alleviating osteoporosis (OP) symptoms. However, active components of OK and the associated molecular mechanisms remain not fully elucidated. AIM OF THE STUDY: This study aims to systematically evaluate the anti-osteoporosis efficacy of OK and for the first time combine network pharmacology with high-throughput whole gene transcriptome sequencing to study its underlying mechanism. MATERIALS AND METHODS: In this study, the osteoporosis model was established by the castration of both ovaries. The level of serum bone turnover factor was detected by enzyme-linked immunosorbent assay. Micro-CT and HE staining were used to observe the changes of bone histopathology, and nano-indentation technique was used to detect the biomechanical properties of rat bone. The main active Chemical components of OK were identified using UPLC-DAD. Efficacy verification and mechanism exploration were conducted by network pharmacology, molecular docking, whole gene transcriptomics and in vivo experiments. RESULTS: In our study, OK significantly improved bone microarchitecture and bone biomechanical parameters in OVX rats, reduced osteoclast indexes such as C-telopeptide of type I collage (CTX-I) and increased Osteoprotegerin (OPG)/Receptor activator of NF-κB ligand (RANKL) levels. Mechanistically, PI3K/AKT pathway was a common pathway for genome enrichment analysis (KEGG) of both network pharmacology and RNA-seq studies. G protein-ß-like protein (GßL), Ribosomal-protein S6 kinase homolog 2 (S6K2), and Phosphoinositide 3-kinase (PI3K) appeared differentially expression in the PI3K-AKT signaling pathway. These results were also confirmed by qRT-PCR and immunohistochemistry. CONCLUSIONS: OK may be used to treat osteoporosis, at least partly by activating PI3K/AKT/mTORC1 signaling pathway.

Mice lacking triglyceride synthesis enzymes in adipose tissue are resistant to diet-induced obesity.

Triglycerides (TGs) in adipocytes provide the major stores of metabolic energy in the body. Optimal amounts of TG stores are desirable as insufficient capacity to store TG, as in lipodystrophy, or exceeding the capacity for storage, as in obesity, results in metabolic disease. We hypothesized that mice lacking TG storage in adipocytes would result in excess TG storage in cell types other than adipocytes and severe lipotoxicity accompanied by metabolic disease. To test this hypothesis, we selectively deleted both TG synthesis enzymes, DGAT1 and DGAT2, in adipocytes (ADGAT DKO mice). As expected with depleted energy stores, ADGAT DKO mice did not tolerate fasting well and, with prolonged fasting, entered torpor. However, ADGAT DKO mice were unexpectedly otherwise metabolically healthy and did not accumulate TGs ectopically or develop associated metabolic perturbations, even when fed a high-fat diet. The favorable metabolic phenotype resulted from activation of energy expenditure, in part via BAT (brown adipose tissue) activation and beiging of white adipose tissue. Thus, the ADGAT DKO mice provide a fascinating new model to study the coupling of metabolic energy storage to energy expenditure.

Ginkgolide attenuates memory impairment and neuroinflammation by suppressing the NLRP3/caspase-1 pathway in Alzheimer's disease.

The NLRP3 inflammasome is involved in the neuroinflammatory pathway of Alzheimer's disease (AD). The aim of this study is to explore the roles and underlying mechanisms of ginkgolide (Baiyu®) on amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice and a murine microglial cell line, BV-2. In the present study, the APP/PS1 mice were administered with ginkgolide, followed by a Morris water maze test. The mice were then euthanized to obtain brain tissue for histological and Aß analysis. Additionally, BV-2 cells were pretreated with ginkgolide and then incubated with Aß1-42 peptide. NLRP3, ASC, and caspase-1 mRNA and protein expression in brain tissue of mice and BV-2 cells were quantified by real-time PCR and western blotting, as well as reactive oxygen species (ROS) production, interleukin (IL)-1ß and IL-18 levels by lucigenin technique and ELISA. Compared with the APP/PS1 mice, ginkgolide-treated mice demonstrated the shortened escape latency, reduced plaques, less inflammatory cell infiltration and neuron loss in the hippocampi of APP/PS1 mice. The levels of NLRP3, ASC, caspase-1, ROS, IL-1ß, and IL-18 were also decreased in the brain tissue of APP/PS1 mice or Aß1-42-treated BV-2 cells following ginkgolide treatment. Ginkgolide exerted protective effects on AD, at least partly by inactivating the NLRP3/caspase-1 pathway.

[Application of single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical trials].

Due to various constraints, such as clinical implementation conditions and unique characteristics of acupuncture-moxibustion, some randomized controlled trials (RCTs) of acupuncture-moxibustion still suffer from relatively low quality and limited applicability. The single-arm objective performance criteria/performance goal can be considered as an ideal supplementary and alternative research approach to RCTs. In this paper, the feasibility of applying the single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical research is explored from the limitations of conducting acupuncture-moxibustion RCTs, the principles, the essential design considerations and key statistical steps. In addition, illustrative examples are provided. The objective is to offer insights into resolving practical difficulties in acupuncture-moxibustion clinical research.

Exploring the impact of professional soccer substitute players on physical and technical performance.

BACKGROUND: Substitutions are generally used to promote the match performance of the whole team. This study aimed to analyze the performance of substitute players and explore the performance difference among substitute players, completed players, and replaced players across each position. METHODS: Chinese Super Soccer League (CSL) matches in the season 2018 including 5871 individual observation from 395 professional soccer players were analyzed by establishing linear mixed models to quantify the performance difference among substitute players (SP) (n = 1,071), entire match players (EMP) (n = 3,454), and replaced players (RP) (n = 1,346), and then separately for each position (central defenders, fullbacks, central midfielders, wide midfielders, and attackers). RESULTS: The results show SP display higher high intensity distance and sprint distance significantly (p < 0.05) relative to playing time than RP and EMP. SP in offensive positions (attackers, wide midfielders) showed significantly higher (p < 0.05) passing and organizing performance such as passes, ball control, short passes, and long passes than RP or EMP. The scoring performances of central midfielders of SP including goals, shots, and shots on target are significantly higher (p < 0.05) than RP or EMP. Central defenders of SP showed higher shot blocks and pass blocks (p < 0.05) while lower passing and organizing performance (p < 0.05). CONCLUSION: Depending on different playing positions, substitute players could indeed improve physical and technical performance related to scoring, passing, and defending as offensive substitute players can boost organizing performance and substitute defenders enhance defending performance. These could help coaches better understand substitute players' influence on match performance and optimize the substitution tactic.

Engineering of cytosine base editors with DNA damage minimization and editing scope diversification.

Cytosine base editors (CBEs), which enable precise C-to-T substitutions, have been restricted by potential safety risks, including DNA off-target edits, RNA off-target edits and additional genotoxicity such as DNA damages induced by double-strand breaks (DSBs). Though DNA and RNA off-target edits have been ameliorated via various strategies, evaluation and minimization of DSB-associated DNA damage risks for most CBEs remain to be resolved. Here we demonstrate that YE1, an engineered CBE variant with minimized DNA and RNA off-target edits, could induce prominent DSB-associated DNA damage risks, manifested as γH2AX accumulation in human cells. We then perform deaminase engineering for two deaminases lamprey LjCDA1 and human APOBEC3A, and generate divergent CBE variants with eliminated DSB-associated DNA damage risks, in addition to minimized DNA/RNA off-target edits. Furthermore, the editing scopes and sequence preferences of APOBEC3A-derived CBEs could be further diversified by internal fusion strategy. Taken together, this study provides updated evaluation platform for DSB-associated DNA damage risks of CBEs and further generates a series of safer toolkits with diversified editing signatures to expand their applications.

C1 Transposterior Arch Lateral Mass Screws Combined With C2 Pedicle Screw and Rod Fixation for Pediatric Atlantoaxial Subluxation: A Minimal 10-Year Follow-up Outcome Analysis.

BACKGROUND AND OBJECTIVES: Although the short-term outcomes of the 1-step reduction and fixation technique using C1 transposterior arch lateral mass screws combined with C2 pedicle screw and rod fixation system for the treatment of pediatric atlantoaxial subluxation (AAS) have been satisfactory, its long-term outcomes and impact on spinal development are not well studied. This study was intended to assess the long-term reliability of this technique for pediatric AAS. METHODS: A retrospective case series study was conducted to analyze the minimum 10-year follow-up outcomes from 7 pediatric patients with AAS who underwent atlantoaxial fusion using the aforementioned technique. Quality of life and cervical range of motion were both measured thoroughly. In addition, vertical growth within the fusion construct (C1-2), overall cervical alignment, and subaxial cervical spine degeneration were evaluated radiographically. RESULTS: The mean age of the 7 patients was 8.14 ± 2.41 (6-12) years at the time of surgery. The mean follow-up period was 11.00 ± 1.15 (10-13) years. No patients presented identifiable intervertebral disk degeneration or segmental instability in the subaxial cervical spine except for 1 patient who showed mild intervertebral disk degeneration. Vertical growth did continue within the atlantoaxial complex after surgery (11.90% ± 2.37%); however, there was a decrease in the percentage of vertical growth compared with the corresponding normal populations of the same age and sex. Moreover, there was a significant decrease in the range of cervical extension and rotation motion, and the overall cervical alignment straightened at the latest follow-up. CONCLUSION: The 1-step reduction and fixation technique is a relatively reliable surgical technique for pediatric AAS, which does not adversely affect the postoperative quality of life or the subaxial cervical degeneration. Nevertheless, certain limitations, such as decreased cervical range of motion and changes in cervical alignment, should be concerned.

Performances and mechanisms of the peroxymonosulfate/ferrate(VI) oxidation process in real shale gas flowback water treatment.

Shale gas flowback water (SGFW), which is an inevitable waste product generated after hydraulic fracturing during development, poses a severe threat to the environment and human health. Managing high-salinity wastewater with complex physicochemical compositions is critical for ensuring environmental sustainability of shale gas development. Desalination processes have been recommended to treat SGFW to adhere to the discharge limits. However, organic fouling has become a significant concern in the steady operation of desalination processes, and the effective removal of organic compounds is challenging. This study aimed to develop an effective oxidation method to mitigate membrane fouling in real SGFW treatment process. It adopted the peroxymonosulfate (PMS)/ferrate (Fe(VI)) process, involving both free and non-free radical pathways that can alleviate the negative effects of high-salinity environments on oxidation. The operating parameters were optimized and removal effects were examined, while the synergistic oxidation mechanism and organic conversion of the PMS/Fe(VI) process were also analyzed. The results showed that the PMS/Fe(VI) process exhibited a synergistic effect compared with the PMS and Fe(VI) processes alone, with a total organic carbon (TOC) removal efficiency of 46.8% under optimal reaction conditions in real SGFW. In the Fe(VI)/PMS process, active species such as Fe(V)/Fe(IV), ·OH, and SO4-· were jointly involved in the oxidation of organic matter. Additionally, 99.5% of the total suspended solids and 95.2% of Ba2+ in the SGFW were removed owing to the formation of a coagulant (Fe3+) and SO42- during the reaction. Finally, an ultrafiltration membrane fouling experiment proved that oxidation processes can increase the membrane-specific flux and alleviate fouling resistance. This study can serve as a reference for the design of real SGFW treatment processes and is significant for the environmental management of shale gas development.

Evaluation of newly-developed glycated hemoglobin clinical analytic reagents and chromatography column on Tosoh HLC-723 G8 Analyzer.

Objective: To evaluate the performance of newly developed glycated hemoglobin (HbA1c) clinical analytic reagents and HPLC columns, applied on Tosoh HLC-723 G8 Analyzer. Methods: Newly developed reagents and columns were used on a Tosoh HLC-723 G8 Analyzer (standard mode) system to measure both of qulity contorls and the clinical blood samples to evaluate the performances of these newly developed prodcuts including precision, accuracy, linearity, carryover, bias evaluation, correlation with commercial reagents, and stability according to CLSI recommendations. Results: The CV of intra-assay precision and inter-assay precision of quality control and clinical blood sample assays using Lirimax products were both less than 3.00%. And the REs of accuracy were less than 6.00%. Linearity: R2 = 0.9993 in the concentration range 4.77%-14.67%. Carryover: 0.05%. The Bland-Altman mean difference: -0.003583% HbA1c (CI: 0.07398: -0.08115); Passing-Bablok regression: y = 1.0022(0.9984:1.006)x-0.01097(-0.03776: 0.01582), R2 = 0.9996. Stability evaluation was also acceptable. Conclusion: The performance of newly developed products was well evaluated for HbA1c measurement on a TOSOH G8 Analyzer which shows excellent suitability for clinical assay.

Leucobacter tenebrionis sp. nov., isolated from the gut of Tenebrio molitor.

A novel Gram-stain-positive bacterium, designated NB10T, was isolated from the gut of Tenebrio molitor. The isolate was rod-shaped, aerobic, non-motile and non-spore-forming. Colonies of strain NB10T were light yellow, circular and smooth. Phylogenetic analysis based on 16S rRNA gene sequence comparisons indicated that the isolate was related to the genus Leucobacter. Its closest relatives were Leucobacter holotrichiae T14T (97.8 % 16S rRNA gene sequence similarity), Leucobacter zeae CC-MF41T (97.0%) and Leucobacter salsicius M1-8T (96.4%). The DNA G+C content of strain NB10T was 68.8 mol%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization values among strain NB10T and the selected Leucobacter species were ≤83.8 % (ANI-blast), 87.6 % (ANI-MUMmer) and 29.6%, which were below the recommended cutoff values for species delineation. The predominant cellular fatty acids were anteiso-C15 : 0 (39.0%), anteiso-C17 : 0 (35.5%) and iso-C16 : 0 (17.0%). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and glycolipids. The predominant respiratory quinones were MK-11 and MK-10. The cell wall amino acids were Gly, Glu, Tr, Ala, and DAB. Based on these phylogenetic and phenotypic results, strain NB10T can be clearly distinguished from all of the recognized species of the genus Leucobacter and is considered to represent a novel species of that genus. The name Leucobacter tenebrionis sp. nov. is proposed, with the type strain NB10T (=MCCC 1K07072T=KCTC 49728T).

Ferroptosis regulator NOS2 is closely associated with the prognosis and cell malignant behaviors of hepatoblastoma: a bioinformatic and in vitro study.

Background: Hepatoblastoma (HB) is the most common liver tumor in children with easy metastasis. The emergence of ferroptosis as a novel form of cell death has gained increased attention in various human cancers. However, the roles of ferroptosis-related (FR) genes in HB remain elusive. Methods: The GSE133039, GSE131329, and GSE81928 datasets were utilized for screening core FR genes in HB. Through Lasso regression analysis and using the support vector machine recursive feature elimination (SVM-RFE) algorithm, three candidate FR genes were obtained for characterizing HB. Their expression patterns and their clinical associations were explored through the 'Limma' R package, and their diagnostic potential was evaluated using ROC curves. Nitric oxide synthase 2 (NOS2) emerged as a candidate for further analyses. The CIBERSORT algorithm and GSEA dataset were used to respectively investigate the immune and metabolism effects of NOS2; the former was validated through immunofluorescence. The GSDC database was employed to analyze the correlation between NOS2 expression and the therapeutic efficacy of multiple drugs. PCR, Western blotting, colony formation assays, and Transwell experiments, were used to determine biological functions of NOS2 in HB cells. Potential upstream transcription factors of NOS2 were predicted through the TRRUST, hTFtarget, GeneCards, and JASPAR databases. Results: NQO1, SLC1A4, and NOS2 were identified as potential genes in HB and found to be significantly upregulated in tumor samples. Nevertheless, only NOS2 was closely associated with HB clinicopathological characteristics; high NOS2 expression indicated poor prognosis, metastatic tendency, and late clinical stage. Immune analyses indicated that high NOS2 expression was concomitant with decreased infiltration levels of CD8+ T cells but increased infiltration levels of macrophages. GSEA revealed that NOS2 failed to affect the enrichments of glycolysis, fatty acid metabolism, and cholesterol biosynthesis in HB. Moreover, NOS2 was positively correlated with the IC50 values of trametinib, lapatinib, and cisplatin. NOS2 overexpression promoted the proliferation, migration and invasion of HepG2 and HuH-6 cells. JUND was identified as a potential transcriptional regulator of NOS2 by binding to its promoter (5'-TTCTGACTCTTTT-3'). Conclusion: NOS2 plays a significant role in HB clinical assessments and holds promise as a novel therapeutic target.

Supervised machine learning improves general applicability of eDNA metabarcoding for reservoir health monitoring.

Effective and standardized monitoring methodologies are vital for successful reservoir restoration and management. Environmental DNA (eDNA) metabarcoding sequencing offers a promising alternative for biomonitoring and can overcome many limitations of traditional morphological bioassessment. Recent attempts have even shown that supervised machine learning (SML) can directly infer biotic indices (BI) from eDNA metabarcoding data, bypassing the cumbersome calculation process of BI regardless of the taxonomic assignment of eDNA sequences. However, questions surrounding the general applicability of this taxonomy-free approach to monitoring reservoir health remain unclear, including model stability, feature selection, algorithm choice, and multi-season biomonitoring. Here, we firstly developed a novel biological integrity index (Me-IBI) that integrates multitrophic interactions and environmental information, based on taxonomy-assigned eDNA metabarcoding data. The Me-IBI can better distinguish the actual health status of the Three Gorges Reservoir (TGR) than physicochemical assessments and have a clear response to human activity. Then, taking this reliable Me-IBI as a supervised label, we compared the impact of selecting different numbers of features and SML algorithms on the stability and predictive performance of the model for predicting ecological conditions in multiple seasons using taxonomy-free eDNA metabarcoding data. We discovered that even with a small number of features, different SML algorithms can establish a stable model and obtain excellent predictive performance. Finally, we proposed a four-step strategy for standardized routine biomonitoring using SML tools. Our study firstly explores the general applicability problem of the taxonomy-free eDNA-SML approach and establishes a solid foundation for the large-scale and standardized biomonitoring application.

Application of laparoscopic backtracking full-thickness continuous everting suture for non-AOSC choledocholithiasis.

BACKGROUND: Based on the current trend of increasing incidence of choledocholithiasis, it is of great significance to explore the closure method of the common bile duct during laparoscopic choledocholithotomy. METHODS: Backtracking full-thickness continuous everting suture was selected for primary closure of the common bile duct suture, while traditional T-tube drainage was selected for the control group. Propensity score matching (PSM) was used to reduce baseline differences between the two groups. RESULT: The intraoperative blood loss, operation time, postoperative recovery speed, postoperative bleeding, postoperative pancreatitis, recurrence rate of bile duct stones, and hospitalization time in the primary closure group were all less than those in the T-tube drainage group. CONCLUSION: Under certain conditions, backtracking full-thickness continuous everting suture could benefit patients with choledocholithiasis compared with traditional T-tube drainage.