Effect of a Forced-Air Warming Blanket on Different Parts of the Body on Core Temperature of Patients Undergoing Elective Open Abdominal Surgery: A Randomized Controlled Single-Blind Trial.

PURPOSE: This study aimed to determine the effect of a forced-air warming blanket placed on different body parts on the core temperature of patients undergoing elective open abdominal surgery. DESIGN: Prospective, single-center, randomized, controlled, single-blind trial. METHODS: A total of 537 patients who underwent open abdominal surgery were randomized into groups A, B, and C and provided with different forced-air warming blankets. Group A was given an upper body blanket, group B a lower body blanket, and group C an underbody blanket. The incidence of intraoperative hypothermia, the time maintaining the core temperature over 36 â„ƒ before hypothermia, the duration of hypothermia, the rewarming rate, and relevant complications were compared among three groups. FINDINGS: Intraoperative hypothermia occurred in 51.4% of patients in group B, 37.6% of patients in group A, and 34.1% of patients in group C (P = .002). Maintaining the core temperature above 36 â„ƒ was longer before hypothermia in groups A and C (log-rank P = .006). In groups A and C, the duration of hypothermia was shorter, the rewarming rate was higher, and the incidence of shivering and postoperative nausea and vomiting were lower, compared to group B. CONCLUSIONS: In patients undergoing elective open abdominal surgery, a forced-air warming blanket on the upper body part or underbody area decreased intraoperative hypothermia, prolonged the time to maintain the core temperature above 36 â„ƒ before hypothermia, and could better prevent further hypothermia when the core temperature had decreased below 36 â„ƒ. In addition, it was significantly superior in reducing shivering and postoperative nausea and vomiting in the postanesthesia care unit.

Screening, expression and anti-tumor functional identification of anti-LAG-3 nanobodies.

OBJECTIVE: To screen and obtain specific anti-lymphocyte activation gene-3 (LAG3) nanobody sequences, purify and express recombinant anti-LAG3 nanobody, and verify its effect on promoting T cells to kill tumor cells. METHODS: Based on the camel derived natural nanobody phage display library constructed by the research group, the biotinylated LAG3 antigen was used as the target, and the anti-LAG3 nanobody sequences were screened by biotin-streptavidin liquid phase screening, phage-ELISA and sequencing. The sequence-conjµgated human IgG1 Fc fragment was obtained, the recombinant anti-LAG3 nanobody expression vector was constructed, the expression of the recombinant anti-LAG3 nanobody was induced by IPTG and purified, and the characteristics and functions of the recombinant anti-LAG3 nanobody were verified by SDS-PAGE, Western blot, cytotoxicity assay, etc. RESULTS: One anti-LAG3 nanobody sequence was successfully screened, and the corresponding recombinant anti-LAG3 nanobody-expressing bacteria were constructed. The results of SDS-PAGE, Western blot and cytotoxicity assay showed that the recombinant anti-LAG3 nanobody was successfully expressed, which was specific, and it could promote the killing ability of T cells against tumor cells, and the optimal concentration was 200 µg/mL. CONCLUSION: The recombinant anti-LAG3 nanobody screened and expressed has specific and auxiliary anti-tumor cell effects, which lays a foundation for its subsequent application.

Interfacial engineering layered bimetallic oxyhydroxides for efficient oxygen evolution reaction.

Transition metal-based oxyhydroxides (MOOH) have garnered significant attention as promising catalyst for the Oxygen Evolution Reaction (OER). However, the direct synthesis of MOOH poses challenges due to the instability of trivalent cobalt and nickel salts, attrivuted to their high oxidation states. In this study, theoretical computations predicted that Co(OH)2 nanosheets are exclusively formed on carbon structures, owing to the stronger binding energy between CoOOH and CC compared to Co(OH)2. Furthermore, the presence of FeOOH interface reduces the binding energy between CoOOH and carbon structure. Experiment evidence confirms that CoOOH can be directly synthesized through controlled epitaxial growth on an FeOOH interface using a hydrothermal method. Moreover, the in-situ doping of iron leads to the formation of high-quality Fe0.35Co0.65OOH with exceptional OER performance, displaying a low overpotential of 240 mV at 10 mA cm-2 and a small Tafel slope of 43 mV dec-1. Density functional theory (DFT) calculations uncover the substantial enhancement of oxygen-containing species adsorption abilities by Fe0.35Co0.65OOH, resulting in improved OER activity. This work presents a promising strategy for the efficient preparation of layered cobalt oxyhydroxides, enabling efficient energy conversion and storage.

Associations of clinical subtypes and bile acid levels of intrahepatic cholestasis of pregnancy with pregnancy outcomes.

Intrahepatic cholestasis of pregnancy (ICP) can lead to many adverse pregnancy outcomes, and the influencing factors remain unclear at present. This study retrospectively analyzed clinical data from 1815 pregnant women with ICP and evaluated the relationship between ICP subtypes, gestational age at onset, and pregnancy outcomes. The results of this study show that during pregnancy, the levels of biochemical indicators (TBA, DBIL and ALT) in the serum of pregnant women initially diagnosed with subtypes of ICP were noted to constantly change, and the subtype of ICP and its severity also changed. The incidence of adverse pregnancy outcomes [meconium-stained amniotic fluid (MSAF), NICU transfer, Apgar score ≤ 7 at 1 min, and preterm birth] in patients with ICP1 (icteric type) was significantly higher than for patients with ICP2, ICP3 or ICP4. The preterm birth rate of early-onset ICP was higher than that of late-onset ICP in ICP1 and ICP3 subtypes. In conclusion, the outcome of pregnancy in women with ICP is closely related to the serum TBA level and ICP subtype, which should be recognized in the clinic.

Therapeutic drug monitoring guidelines in oncology: what do we know and how to move forward? Insights from a systematic review.

Background: Compared with anti-infective drugs, immunosuppressants and other fields, the application of therapeutic drug monitoring (TDM) in oncology is somewhat limited. Objective: We aimed to provide a comprehensive understanding of TDM guidelines for antineoplastic drugs and to promote the development of individualized drug therapy in oncology. Design: This study type is a systematic review. Data sources and methods: This study was performed and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 statement. Databases including PubMed, Embase, the official websites of TDM-related associations and Chinese databases were comprehensively searched up to March 2023. Two investigators independently screened the literature and extracted data. The methodological and reporting quality was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) and the Reporting Items for Practice Guidelines in Healthcare (RIGHT), respectively. Recommendations and quality evaluation results were presented by visual plots. This study was registered in PROSPERO (No. CRD42022325661). Results: A total of eight studies were included, with publication years ranging from 2014 to 2022. From the perspective of guideline development, two guidelines were developed using evidence-based methods. Among the included guidelines, four guidelines were for cytotoxic antineoplastic drugs, three for small molecule kinase inhibitors, and one for antineoplastic biosimilars. Currently available guidelines and clinical practice provided recommendations of individualized medication in oncology based on TDM, as well as influencing factors. With regard to methodological quality based on AGREE II, the average overall quality score was 55.21%. As for the reporting quality by RIGHT evaluation, the average reporting rate was 53.57%. Conclusion: From the perspective of current guidelines, TDM in oncology is now being expanded from cytotoxic antineoplastic drugs to newer targeted treatments. Whereas, the types of antineoplastic drugs involved are still small, and there is still room for quality improvement. Furthermore, the reflected gaps warrant future studies into the exposure-response relationships and population pharmacokinetics models.

[Evaluation of nutritional value of Bambusae Concretio Silicea based on content of 15 amino acids].

The content of 15 total amino acids(TAAs) in Bambusae Concretio Silicea was determined by HPLC with phenyl-isothiocyanate(PITC) for pre-column derivatization. The results showed that the content of TAA was 0.61-12.25 mg·g~(-1), and aspartic acid(Asp), glutamic acid(Glu), proline(Pro), glycine(Gly), and valine(Val) were the top five amino acids in terms of the average content. The content of essential amino acids(EAAs), conditionally essential amino acids(CEAAs), non-essential amino acids(NEAAs), and medicinal amino acids(MAAs) was 0.24-4.75, 0.30-4.73, 0.40-7.50, and 0.36-6.51 mg·g~(-1), respectively. Among the delicious amino acids, sweet amino acids(SAA), bitter amino acids(BAA), fresh-taste amino acids(FAAs), and odourless amino acids(OAAs) had the content of 0.22-4.70, 0.19-4.03, 0.13-2.26, and 0.06-1.26 mg·g~(-1), respectively. The 21 batches of Bambusae Concretio Silicea samples presented the same composition but significant differences in the content of amino acids. Among the three producing areas, Guangdong was the area where the samples had the highest content of TAAs, EAAs, CEAAs, NEAAs, MAAs, and delicious amino acids. Furthermore, the ratio of amino acid(RAA), ratio coefficient of amino acid(RCAA), and score of ratio coefficient of amino acid(SRCAA) were calculated to evaluate the nutritional value of Bambusae Concretio Silicea. The results showed that the Bambusae Concretio Silicea samples from Guangdong had better nutritional value. The nutritional value evaluation based on the content of 15 amino acids was proposed to provide data support for the quality grading of Bambusae Concretio Silicea and lay a foundation for the development and utilization of the medicinal material resources.

CD73 polymorphisms are associated with schizophrenia.

Ecto-5'-nucleotidase/CD73 enzyme plays a key role in the regulation of extracellular adenosine levels, thereby exerting influence on adenosine homeostasis. Emerging evidence suggests that perturbations in purines and ecto-5'-nucleotidase activity are associated with an augmented susceptibility to schizophrenia. However, the precise impact of genetic variations in CD73 on individuals with schizophrenia remains poorly understood. Here, our study demonstrated that rs3734442 allele and rs4431401 heterozygote were conferred a significant risk of schizophrenia disease (rs3734442: odds ratio, 0.556; 95% CI, 0.375 to 0.825; p = 0.004; rs4431401: odds ratio, 1.881, 95% CI, 1.117 to 3.166; p = 0.020). Comparing different genders, we observed a significant association between rs3734442 genotypes and male cases (rs3734442: odds ratio, 0.452; 95% CI, 0.257 to 0.796; p = 0.007). Likewise, there was a significant association between rs4431401 genotypes and male patients (rs4431401: odds ratio, 2.570; 95% CI, 1.196 to 5.522; p = 0.015). Based on family history and antipsychotics medication usage, our data reveals that the rs9444348 allele exhibits the most significant association with familial susceptibility to schizophrenia (odds ratio, 1.541; 95% CI, 1.009 to 2.353; p = 0.048 for A vs G). Moreover, individuals carrying variants of rs6922, rs2229523, and rs2065114 while being treated with clozapine demonstrate a higher frequency proportion compared to those receiving risperidone treatment (p = 0.035; p = 0.049; p = 0.027 respectively). Additionally, our results indicate that patients with GG genotype of rs9444348 had significantly higher likelihood of using clozapine instead of sulpiride (p = 0.048). Overall, our data strongly suggest that genetic variations in CD73 are significantly associated with schizophrenia risk and may serve as valuable resources for identifying therapeutic targets.

Ring-Opening Coupling of Cyclopropanol with 1,2,3-Triazole for the Synthesis of Fused Triazoles.

A radical ring-opening arylation of cyclopropanol with 1,2,3-triazole has been achieved. This synthetic protocol provides straightforward access to a wide range of structurally diverse and chiral 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyridines with high efficiency from readily available chiral cyclopropanols.

Ocular dominance-dependent binocular combination of monocular neuronal responses in macaque V1.

Primates rely on two eyes to perceive depth, while maintaining stable vision when either one eye or both eyes are open. Although psychophysical and modeling studies have investigated how monocular signals are combined to form binocular vision, the underlying neuronal mechanisms, particularly in V1 where most neurons exhibit binocularity with varying eye preferences, remain poorly understood. Here, we used two-photon calcium imaging to compare the monocular and binocular responses of thousands of simultaneously recorded V1 superficial-layer neurons in three awake macaques. During monocular stimulation, neurons preferring the stimulated eye exhibited significantly stronger responses compared to those preferring both eyes. However, during binocular stimulation, the responses of neurons preferring either eye were suppressed on the average, while those preferring both eyes were enhanced, resulting in similar neuronal responses irrespective of their eye preferences, and an overall response level similar to that with monocular viewing. A neuronally realistic model of binocular combination, which incorporates ocular dominance-dependent divisive interocular inhibition and binocular summation, is proposed to account for these findings.

VDR promotes pancreatic cancer progression in vivo by activating CCL20-mediated M2 polarization of tumor associated macrophage.

BACKGROUND: Activation of VDR pathway was a promising anti-tumor therapy strategy. However, numerous clinical studies have demonstrated the effect of activating VDR is limited, which indicates that VDR plays a complex role in vivos. METHODS: We analyzed the TCGA database to examine the association between VDR expression and immune cell infiltration in pancreatic adenocarcinoma (PAAD). Western blot, ELISA, ChIP, and dual-luciferase reporter assays were performed to determine the mechanism of VDR regulating CCL20. Migration assay and immunofluorescence were used to investigate the role of CCL20 in M2 macrophage polarization and recruitment. We employed multiplexed immunohistochemical staining and mouse models to validate the correlation of VDR on macrophages infiltration in PAAD. Flow cytometry analysis of M2/M1 ratio in subcutaneous graft tumors. RESULTS: VDR is extensively expressed in PAAD, and patients with elevated VDR levels exhibited a significantly reduced overall survival. VDR expression in PAAD tissues was associated with increased M2 macrophages infiltration. PAAD cells overexpressing VDR promote macrophages polarization towards M2 phenotype and recruitment in vitro and vivo. Mechanistically, VDR binds to the CCL20 promoter and up-regulates its transcription. The effects of polarization and recruitment on macrophages can be rescued by blocking CCL20. Finally, the relationship between VDR and M2 macrophages infiltration was evaluated using clinical cohort and subcutaneous graft tumors. A positive correlation was demonstrated between VDR/CCL20/CD163 in PAAD tissues and mouse models. CONCLUSION: High expression of VDR in PAAD promotes M2 macrophage polarization and recruitment through the secretion of CCL20, which activates tumor progression. This finding suggests that the combination of anti-macrophage therapy may improve the efficacy of VDR activation therapy in PAAD.

Repeat corneal transplantation in Southern China: Indications, surgical technique, outcomes, and risk factors for repeat keratoplasty failure.

PURPOSE: To report the indications, surgical techniques, and outcomes of repeat keratoplasty and evaluate the risk factors for graft failure in the Chinese population. METHODS: The medical records of 216 patients (243 cases) who underwent at least two keratoplasties at a leading eye hospital in southern China between 2011 and 2020 were retrospectively reviewed. Indications and surgical procedures for repeat corneal transplantation were analyzed. Kaplan-Meier survival analysis was used to determine the graft survival rate after repeat keratoplasty. A multivariable survival model was used to assess the risk factors. RESULTS: Repeated keratoplasties increased continuously from 2011 to 2020 (P = 0.002). The most common primary indication was infectious keratitis (38.7%), and the most common reason for repeat keratoplasty was graft rejection (30.04%). Regraft techniques included penetrating keratoplasty (PK) in 165 cases (67.9%), deep lamellar keratoplasty (DALK) in 52 cases (21.40%), and endothelial keratoplasty (EK) in 26 cases (10.7%). Median survival was 5.3, 6.8, and 6.4 years for PK, DALK, and EK, respectively. The 5-year survival rate was 53.5%, 66.6%, and 69.8% for PK, DALK, and EK, respectively. The median LogMAR visual acuity was 1.4 for PK, 0.75 for DALK, and 1.2 for EK at the end of the follow-up. Multivariate analysis revealed that graft rejection is a risk factor for repeat keratoplasty failure (P = 0.002). CONCLUSIONS: DALK and EK may provide better outcomes than PK in treating graft failure. Preventing and treating postoperative graft rejection may be key to improving regraft survival. These findings will aid in the management of failed corneal grafts.

Unveiling the methionine cycle: a key metabolic signature and NR4A2 as a methionine-responsive oncogene in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.

Bombyx mori triose-phosphate transporter protein inhibits Bombyx mori nucleopolyhedrovirus infection by reducing the cell glycolysis pathway.

Bombyx mori triose-phosphate transporter protein (BmTPT) is a member of the solute carrier (SLC) family. Its main function is to transport triose phosphate between intracellular and extracellular. In this study, BmTPT was cloned and characterised from the fat body of the silkworm Bombyx mori, resulting in an open reading frame (ORF) with a full length of 936 bp, which can encode 311 amino acid residues and has eight transmembrane structural domains. BmTPT was distributed throughout the cell and deposited the most in the nucleus, and is expressed in all tissues of Bombyx mori. Bombyx mori nucleopolyhedrovirus (BmNPV) infection significantly up-regulated BmTPT expression in immune tissue fat bodies. In addition, overexpression of BmTPT significantly inhibited BmNPV infection and markedly reduced the expression of enzymes related to the cellular glycolytic pathway; on the contrary, down-regulation of BmTPT expression by RNA interference resulted in robust replication of BmNPV and a significant increase in the expression of enzymes related to the cellular glycolytic pathway. This is the first report that BmTPT has antiviral effect in silkworm, and also could result in a lack of energy and raw materials for BmNPV replication and infection through down-regulation of the cellular glycolytic pathway.

CPhaMAS: An online platform for pharmacokinetic data analysis based on optimized parameter fitting algorithm.

BACKGROUND AND OBJECTIVE: Clinical pharmacological modeling and statistical analysis software is an essential basic tool for drug development and personalized drug therapy. The learning curve of current basic tools is steep and unfriendly to beginners. The curve is even more challenging in cases of significant individual differences or measurement errors in data, resulting in difficulties in accurately estimating pharmacokinetic parameters by existing fitting algorithms. Hence, this study aims to explore a new optimized parameter fitting algorithm that reduces the sensitivity of the model to initial values and integrate it into the CPhaMAS platform, a user-friendly online application for pharmacokinetic data analysis. METHODS: In this study, we proposed an optimized Nelder-Mead method that reinitializes simplex vertices when trapped in local solutions and integrated it into the CPhaMAS platform. The CPhaMAS, an online platform for pharmacokinetic data analysis, includes three modules: compartment model analysis, non-compartment analysis (NCA) and bioequivalence/bioavailability (BE/BA) analysis. Our proposed CPhaMAS platform was evaluated and compared with existing WinNonlin. RESULTS: The platform was easy to learn and did not require code programming. The accuracy investigation found that the optimized Nelder-Mead method of the CPhaMAS platform showed better accuracy (smaller mean relative error and higher R2) in two-compartment and extravascular administration models when the initial value was set to true and abnormal values (10 times larger or smaller than the true value) compared with the WinNonlin. The mean relative error of the NCA calculation parameters of CPhaMAS and WinNonlin was <0.0001 %. When calculating BE for conventional, high-variability and narrow-therapeutic drugs. The main statistical parameters of the parameters Cmax, AUCt, and AUCinf in CPhaMAS have a mean relative error of <0.01% compared to WinNonLin. CONCLUSIONS: In summary, CPhaMAS is a user-friendly platform with relatively accurate algorithms. It is a powerful tool for analysing pharmacokinetic data for new drug development and precision medicine.

Enhanced SSD framework for detecting defects in cigarette appearance using variational Bayesian inference under limited sample conditions.

In high-speed cigarette manufacturing industries, occasional minor cosmetic cigarette defects and a scarcity of samples significantly hinder the rapid and accurate detection of defects. To tackle this challenge, we propose an enhanced single-shot multibox detector (SSD) model that uses variational Bayesian inference for improved detection of tiny defects given sporadic occurrences and limited samples. The enhanced SSD model incorporates a bounded intersection over union (BIoU) loss function to reduce sensitivity to minor deviations and uses exponential linear unit (ELU) and leaky rectified linear unit (ReLU) activation functions to mitigate vanishing gradients and neuron death in deep neural networks. Empirical results show that the enhanced SSD300 and SSD512 models increase the model's detection accuracy mean average precision (mAP) by up to 1.2% for small defects. Ablation studies further reveal that the model's mAP increases by 1.5%, which reduces the computational requirements by 5.92 GFLOPs. The model also shows improved inference in scenarios with limited samples, thus highlighting its effectiveness and applicability in high-speed, precision-oriented cigarette manufacturing industries.

Characterizing the Efficacy and Safety of Chemotherapy Plus Everolimus in HER2-Negative Metastatic Breast Cancer Harboring Altered PI3K/AKT/mTOR.

BACKGROUND: The clinical outcomes of chemotherapy (CT) for the treatment of metastatic triple-negative (TN) and hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) have proven to be disappointing. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, a tumor-promoting signaling cascade frequently mutated in breast cancer (BC), has been implicated in chemoresistance. In this study, our objective is to investigate the efficacy and safety of combining everolimus with chemotherapy in mBC patients exhibiting mutations in the PI3K/AKT/mTOR pathway. METHODS: We conducted a retrospective analysis to characterize the efficacy, safety, and their association with clinical and molecular characteristics of metastatic lesions in 14 patients with HER2- mBC. These patients harbored at least one altered member of the PI3K/AKT/mTOR signaling pathway and were treated with a combination of a chemotherapy agent and the mTOR inhibitor everolimus (CT+EVE). RESULTS: The majority of patients belonged to the triple-negative (TN) subtype (9/14, 64.3%), having already undergone 2 lines of chemotherapy (CT) in the metastatic setting (11, 78.6%). These patients carried altered phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and were administered a vinorelbine-containing regimen (10, 71.4%). The objective response rate (ORR) was 42.9%, with a disease control rate of 92.9%. The median progression-free survival (PFS) and overall survival (OS) were 5.9 (95% confidence interval (CI): 4.9-13.6) months and 14.3 (95% CI: 8.5-not reached (NR)) months, respectively. Patients with fewer prior treatment lines tended to exhibit longer PFS. OS, PFS, and ORR were comparable between hormone receptor-positive (HR+) and triple-negative breast cancer (TNBC) patients, but numerical improvements were noted in patients with a single PI3K pathway alteration compared to those with more than one alteration. Genomic alterations that surfaced upon progression on CT+EVE included cyclin dependent kinase 4 (CDK4) and epidermal growth factor receptor (EGFR) amplification, as well as neurofibromin 1 (NF1) mutation, suggesting potential mechanisms of acquired resistance. An analysis of adverse events indicated manageable toxicities. CONCLUSIONS: The findings of this study suggest both activity and safety for the combination of chemotherapy and the mTOR inhibitor everolimus (CT+EVE) in patients with HER2- mBC who have alterations in the PI3K pathway, particularly those who have received fewer prior chemotherapy. However, it is crucial to note that large-scale, randomized control studies are warranted to more comprehensively characterize the efficacy and safety of this combination therapy.

Ensemble learning for integrative prediction of genetic values with genomic variants.

BACKGROUND: Whole genome variants offer sufficient information for genetic prediction of human disease risk, and prediction of animal and plant breeding values. Many sophisticated statistical methods have been developed for enhancing the predictive ability. However, each method has its own advantages and disadvantages, so far, no one method can beat others. RESULTS: We herein propose an Ensemble Learning method for Prediction of Genetic Values (ELPGV), which assembles predictions from several basic methods such as GBLUP, BayesA, BayesB and BayesCπ, to produce more accurate predictions. We validated ELPGV with a variety of well-known datasets and a serious of simulated datasets. All revealed that ELPGV was able to significantly enhance the predictive ability than any basic methods, for instance, the comparison p-value of ELPGV over basic methods were varied from 4.853E-118 to 9.640E-20 for WTCCC dataset. CONCLUSIONS: ELPGV is able to integrate the merit of each method together to produce significantly higher predictive ability than any basic methods and it is simple to implement, fast to run, without using genotype data. is promising for wide application in genetic predictions.

Toward Genetic Testing of Rivaroxaban? Insights from a Systematic Review on the Role of Genetic Polymorphism in Rivaroxaban Therapy.

BACKGROUND: Investigations into the rivaroxaban response from the perspective of genetic variation have been relatively recent and wide in scope, whereas there is no consensus on the necessity of genetic testing of rivaroxaban. Thus, this systematic review aims to thoroughly evaluate the relationship between genetic polymorphisms and rivaroxaban outcomes. METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Chinese databases were searched to 23 October 2022. We included cohort studies reporting the pharmacogenetic correlation of rivaroxaban. Outcomes measured included efficacy (all-cause mortality, thromboembolic events and coagulation-related tests), safety (major bleeding, clinically relevant non-major bleeding [CRNMB] and any hemorrhage), and pharmacokinetic outcomes. A narrative synthesis was performed to summarize findings from individual studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and the reporting guideline for Synthesis Without Meta-Analysis. RESULTS: A total of 12 studies published between 2019 and 2022 involving 1364 patients were included. Ten, one, and six studies focused on the ABCB1, ABCG2, and CYP gene polymorphisms, respectively. Pharmacokinetic outcomes accounted for the majority of the outcomes reported (n = 11), followed by efficacy (n = 5) [including prothrombin time (PT) or international normalized ratio (n = 3), platelet inhibition rate (PIR) or platelet reactivity units (PRUs; n = 1), thromboembolic events (n = 1)], and safety (n = 5) [including major bleeding (n = 2), CRNMB (n = 2), any hemorrhage (n = 1)]. For ABCB1 gene polymorphism, the relationship between PT and ABCB1 rs1045642 was inconsistent across studies, however there was no pharmacogenetic relationship with other efficacy outcomes. Safety associations were found in ABCB1 rs4148738 and major bleeding, ABCB1 rs4148738 and CRNMB, ABCB1 rs1045642 and CRNMB, and ABCB1 rs2032582 and hemorrhage. Pharmacokinetic results were inconsistent among studies. For ABCG2 gene polymorphism, no correlation was observed between ABCG2 rs2231142 and dose-adjusted trough concentration (Cmin/D). For CYP gene polymorphisms, PIR or PRUs have a relationship with CYP2C19 rs12248560, however bleeding or pharmacokinetic effects did not show similar results. CONCLUSIONS: Currently available data are insufficient to confirm the relationship between clinical or pharmacokinetic outcomes of rivaroxaban and gene polymorphisms. Proactive strategies are advised as a priority in clinical practice rather than detection of SNP genotyping. CLINICAL TRIALS REGISTRATION: PROSPERO registration number CRD42022347907.

N6-methyladenosine (m6A) sequencing reveals Heterodera glycines-induced dynamic methylation promoting soybean defense.

Unraveling the intricacies of soybean cyst nematode (Heterodera glycines) race 4 resistance and susceptibility in soybean breeding lines-11-452 (highly resistant) and Dongsheng1 (DS1, highly susceptible)-was the focal point of this study. Employing cutting-edge N6-methyladenosine (m6A)-seq and RNA-seq techniques, we delved into the impact of m6A modification on gene expression and plant defense responses. Through the evaluation of nematode development in both resistant and susceptible roots, a pivotal time point (3 days post inoculation) for m6A methylation sequencing was identified. Our sequencing data exhibited robust statistics, successful soybean genome mapping, and prevalent m6A peak distributions, primarily in 3'UTR (Untranslated region) and stop codon regions. Analysis of differentially expressed m6A peaks (DMPs) and expressed genes (DEGs) revealed distinctive patterns between resistant and susceptible genotypes. In the highly resistant line (11-452), key resistance and defense-associated genes displayed increased expression coupled with inhibited methylation, encompassing crucial players like R genes, receptor kinases, and transcription factors. Conversely, the highly susceptible DS1 line exhibited heightened expression correlated with decreased methylation in genes linked to susceptibility pathways, including Mildew Locus O (MLO)-like proteins and regulatory elements affecting defense mechanisms. Genome-wide assessments, GO/KEGG analyses, and DMP/DEG overlap emphasized the intricate interplay of m6A modifications, alternative splicing, microRNA and gene regulation in plant defense. Protein-protein interaction networks illuminated defense-pivotal genes, delineating divergent mechanisms in resistant and susceptible responses. This study sheds light on the dynamic correlation between methylation, splicing, and gene expression, providing profound insights into plant responses to nematode infection.

Identification of groundwater pollution sources and health risk assessment in the Fengshui mining area of Central Shandong, China.

The crux of groundwater protection lies in a profound understanding of the sources of pollutants and their impacts on human health. This study selected 47 groundwater samples from the Fengshui mining area in central Shandong Province, China, employing advanced hydrogeochemical techniques, positive matrix factorization (PMF), and Monte Carlo analysis methods, aimed at unveiling the characteristics, origins, and health risks of water pollutants. The results indicated that the majority of samples exhibited a slightly alkaline nature. Notably, the concentrations of fluoride (F-) and nitrate (NO3-) exceeded China's safety standards in 40.43% and 23.40% of the samples, respectively. Moreover, a water quality index (WQI) below 50 was observed in approximately 68.09% of the sites, suggesting that the water quality in these areas generally met acceptable levels. However, regions with higher WQI values were predominantly located in the northern and southern parts of the mining area. PMF analysis revealed that regional geological and industrial activities were the primary factors affecting water quality, followed by mining discharges, fundamental geological and agricultural processes, and leachate enrichment activities. The health risk assessment highlighted the heightened sensitivity of the youth demographic to fluoride, with a more pronounced non-carcinogenic risk compared to nitrate, affecting about 31.89% of the youth population. Hence, it is imperative for local authorities and relevant departments to take prompt actions to remediate groundwater contamination to minimize public health risks.