Identification of Escherichia coli strains using MALDI-TOF MS combined with long short-term memory neural networks.

The current study aims to develop a new technique for the precise identification of Escherichia coli strains, utilizing matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) combined with a long short-term memory (LSTM) neural network. A total of 48 Escherichia coli strains were isolated and cultured on tryptic soy agar medium for 24 hours for the generation of MALDI-TOF MS spectra. Eight hundred MALDI-TOF MS spectra were obtained per strain, resulting in a database of 38,400 spectra. Fifty percent of the data was utilized for LSTM neural network training, with fine-tuned parameters for strain-level identification. The other half served as the test set to assess model performance. Traditional PCA dimension reduction of MALDI-TOF MS spectra indicated 47 out of 48 strains to be unclassifiable. In contrast, the LSTM neural network demonstrated remarkable efficacy. After 20 training epochs, the model achieved a loss value of 0.0524, an accuracy of 0.999, a precision of 0.985, and a recall of 0.982. When tested on the unseen data, the model attained an overall accuracy of 92.24%. The integration of MALDI-TOF MS and LSTM neural network markedly enhances the identification of Escherichia coli strains. This innovative approach offers an effective and accurate tool for MALDI-TOF MS-based strain-level identification, thus expanding the analytical capabilities of microbial diagnostics.

NIR Light and GSH Dual-Responsive Upconversion Nanoparticles Loaded with Multifunctional Platinum(IV) Prodrug and RGD Peptide for Precise Cancer Therapy.

Platinum(II) drugs as a first-line anticancer reagent are limited by side effects and drug resistance. Stimuli-responsive nanosystems hold promise for precise spatiotemporal manipulation of drug delivery, with the aim to promote bioavailability and minimize side effects. Herein, a multitargeting octahedral platinum(IV) prodrug with octadecyl aliphatic chain and histone deacetylase inhibitor (phenylbutyric acid, PHB) at axial positions to improve the therapeutic effect of cisplatin was loaded on the upconversion nanoparticles (UCNPs) through hydrophobic interaction. Followed attachment of DSPE-PEG2000 and arginine-glycine-aspartic (RGD) peptide endowed the nanovehicles with high biocompatibility and tumor specificity. The fabricated nanoparticles (UCNP/Pt(IV)-RGD) can be triggered by upconversion luminescence (UCL) irradiation and glutathione (GSH) reduction to controllably release Pt(II) species and PHB, inducing profound cytotoxicity. Both in vitro and in vivo experiments demonstrated that UCNP/Pt(IV)-RGD exhibited remarkable antitumor efficiency, high tumor-targeting specificity, and real-time UCL imaging capacity, presenting an intelligent platinum(IV) prodrug-loaded nanovehicle for UCL-guided dual-stimuli-responsive combination therapy.

The efficacy of acupuncture for trigeminal neuralgia: an overview of systematic reviews.

Background: Many systematic reviews (SRs) and meta-analysis (MAs) have reported the efficacy of acupuncture treatment for primary trigeminal neuralgia (PTN), but the quality of evidence is unknown and therefore needs to be evaluated comprehensively. Methods: Eight electronic databases were searched from their inception until January 5, 2024. The methodological quality, reporting quality, and risk of bias of the included SRs were assessed by the assessment of multiple systematic reviews 2 (AMSTAR-2), the Risk of Bias in Systematic Reviews (ROBIS) tool, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The quality of evidence for outcome measures was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: We identified 13 SRs/MAs met inclusion criteria. According to the results of the AMSTAR-2, six were rated as critically low quality and seven as low quality. According to ROBIS assessment, 8 SRs/MAs were classified as low risk, and 5 SRs/MAs were found to be high risk. The PRISMA report still has some reporting deficiencies in aspects such as protocol and registration, search strategy, risk of bias, additional analyzes and funding. According to the GRADE system, no high-quality evidence was found, 1 was of moderate quality, 4 were of low quality, and 8 were of critical low quality. Conclusion: Based on the evidence collected, acupuncture shows promise as a treatment for PTN patients. However, it is important to note that the included SRs/MAs generally have low methodological quality and evidence quality. Therefore, caution must be exercised when interpreting this conclusion. To enhance future research in this area, it is recommended to adequately report methodological details and adhere to guidelines for conducting SRs/MAs.Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024499280.

[Coronary heart disease: innovative understanding from traditional Chinese medicine and treatment by classic formulas].

Coronary heart disease is a common cardiovascular disease, attacking about 11.4 million patients in China. With increasing prevalence and mortality year by year, coronary heart disease has become a major factor threatening human health and public health. Although primary and secondary prevention, intervention, coronary artery bypass grafting and other interventions have reduced the death rate, there are drug(aspirin) resistance, secondary nitroglycerin failure, post-intervention fatigue, chest tightness, and an-xiety, and complication with a high risk of bleeding, which have become the key clinical and scientific issues needed to be resolved. Coronary heart disease belongs to the category of chest impediment and heart pain in traditional Chinese medicine(TCM). The TCM etiology of this disease includes external contraction of cold, emotional disorders, constitutional insufficiency, physical weakness, and labor injury, which are closely related to sympathetic nerve activity, state of cardiac and psychological diseases, family history, and cardiovascular metabolic disorders in modern medicine. The TCM causes of coronary heart disease include Qi depression, phlegm turbidity, blood stasis, fire-heat, cold congealing, and healthy Qi deficiency, which are associated with emotional factors such as anxiety and depression, abnormal lipid metabolism, abnormalities in blood circulation and coagulation, inflammatory responses, hyperactive immune responses, and heart failure, chronic wasting disease, or aging, respectively. Accordingly, the patients with Qi depression should be treated with Chaihu Longgu Muli Decoction, and those with phlegm turbidity should be treated with Wendan Decoction and Gualou Xiebai Banxia Decoction. Xuefu Zhuyu Decoction and Guizhi Fuling Pills are recommended for blood stasis, Xiaoxianxiong Decoction and Sanhuang Xiexin Decoction for fire-heat, Zhishi Xiebai Guizhi Decoction for cold congealing, and Renshen Decoction for healthy Qi deficiency. Due to the changes in the spectrum of diseases from ancient to modern times as well as the differences in physical constitution, the key cause of coronary heart disease has evolved from the chest Yang deficiency and cold congealing to Qi depression, phlegm turbidity, phlegm combined with stasis, and fire-heat, showing a shift from cold to heat and from deficiency to excess. The combination of classic formulas presents a pattern. That is, the core formula-syndrome correspondence of a disease often fixedly appears with other formula-syndrome correspondence, which may be related to the development of the pathophysiological mechanism of the disease. In the clinical application of modern pharmacological results, the research team has formulated the clinical principle of pathogenesis corresponding to pathological changes and medicinal nature corresponding pharmacological effects. The modern pharmacological research on classic formulas is conducive to targeted treatment. Moreover, classic formulas help to ameliorate aspirin resistance, clopidogrel resistance, post-intervention anxiety, and high risk of bleeding and address the lack of effective blockade of critical lesions in the coronary artery and the progression of post-infarction heart failure. The innovative understanding of the etiology and pathogenesis of co-ronary heart disease helps to improve the clinical efficacy of TCM and the clinical system for treating coronary heart disease with classic formulas.

Accurate and affordable detection of rifampicin and isoniazid resistance in Tuberculosis sputum specimens by multiplex PCR-multiple probes melting analysis.

BACKGROUND: Escalating cases of multidrug-resistant tuberculosis (MDR-TB) pose a major challenge to global TB control efforts, necessitating innovative diagnostics to empower decentralized detection of gene mutations associated with resistance to rifampicin (RIF) and isoniazid (INH) in Mycobacterium tuberculosis (M. tuberculosis) in resource-constrained settings. METHODS: Combining multiplex fluorescent PCR and Multiple Probes Melting Analysis, we identified mutations in the rpoB, katG, ahpC and inhA genes from sputum specimens. We first constructed a reference plasmid library comprising 40 prevalent mutations in the target genes' resistance determining regions and promoters, serving as positive controls. Our assay utilizes a four-tube asymmetric PCR method with specifically designed molecular beacon probes, enabling simultaneous detection of all 40 mutations. We evaluated the assay's effectiveness using DNA isolated from 50 clinically confirmed M. tuberculosis sputum specimens, comparing our results with those obtained from Sanger sequencing and retrospective validation involving bacteriological culture and phenotypic drug susceptibility testing (pDST). We also included the commercial Xpert MTB/RIF assay for accuracy comparison. RESULTS: Our data demonstrated remarkable sensitivity in detecting resistance to RIF and INH, achieving values of 93.33% and 95.24%, respectively, with a specificity of 100%. The concordance between our assay and pDST was 98.00%. Furthermore, the accuracy of our assay was comparable to both Sanger sequencing and the Xpert assay. Importantly, our assay boasts a 4.2-h turnaround time and costs only $10 per test, making it an optimal choice for peripheral healthcare settings. CONCLUSION: These findings highlight our assay's potential as a promising tool for rapidly, accurately, and affordably detecting MDR-TB.

Identification of Angiogenesis-Related Genes and Molecular Subtypes for Psoriasis Based on Random Forest Algorithm.

Psoriasis is a chronic immune-mediated recurrent skin disease causing systemic damage. Increased angiogenesis has been reported to participate in the progression of psoriasis. However, angiogenesis-related genes (ARGs) in psoriasis have not been systematically elucidated. Therefore, we aim to identify potential biomarkers and subtypes using two algorithms. Transcriptome sequencing data of patients with psoriasis were obtained, in which differentially expressed genes were assessed by principal component analysis (PCA). A diagnostic model was developed using random forest algorithm (ntree=400) and validated by ROC curves. Subsequently, we performed consensus clustering to calculate angiogenesis-associated molecular subtypes of psoriasis. Additionally, a correlation analysis was conducted between ARGs and immune cell infiltration. Finally, validation of potential ARG genes was performed by qRT-PCR. We identified 29 differentially expressed ARGs, including 13 increased and 16 decreased. Ten ARGs, CXCL8, ANG, EGF, HTATIP2, ANGPTL4, TNFSF12, RHOB, PML, FOXO4, and EMCN were subsequently sifted by the diagnostic model based on a random forest algorithm. Analysis of the ROC curve (area under the curve [AUC] = 1.0) indicated high diagnostic performance in internal validation. The correlation analysis suggested that CXCL8 has a high positive correlation with neutrophil (R =0.8, P<0.0001) and interleukins pathway (R=0.79, P<0.0001). Furtherer, two ARG-mediated subtypes were obtained, indicating potential heterogeneity. Finally, the qRT-PCR demonstrated that the mRNA expression levels of CXCL8 and ANGPTL4 were elevated in psoriasis patients, with a reduced expression of EMCN observed. The current paper indicated potential ARG-related biomarkers of psoriasis, including CXCL8, ANGPTL4, and EMCN, with two molecular subtypes.

[Value of single-phase gonadotropin-releasing hormone stimulation test in diagnosis of central precocious puberty in girls with different levels of body mass index]. / 单时相GnRHæ¿€å‘è¯•éªŒå¯¹ä¸åŒä½“é‡æŒ‡æ•°å¥³ç«¥ä¸­æž¢æ€§æ€§æ—©ç†Ÿè¯Šæ–­ä»·å€¼çš„ç ”ç©¶.

OBJECTIVES: To investigate the value of single-phase gonadotropin releasing hormone (GnRH) stimulation test in the diagnosis of central precocious puberty (CPP) in girls with different levels of body mass index (BMI). METHODS: A retrospective analysis was performed for the data of 760 girls with breast development before 7.5 years of age who attended the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2023. According to the results of GnRH stimulation test and clinical manifestations, they were divided into a CPP group (297 girls) and a non-CPP group (463 girls). According to the values of BMI, the girls were divided into a normal weight group (540 girls), an overweight group (116 girls), and an obese group (104 girls). The receiver operating characteristic (ROC) curve was used to investigate the value of single-phase GnRH stimulation test in the diagnosis of CPP in girls with different levels of BMI. RESULTS: Luteinizing hormone (LH)/follicle-stimulating hormone at 30 minutes after GnRH stimulation had an area under the curve (AUC) of 0.985 in the diagnosis of CPP, which was higher than the AUC at 0, 60, and 90 minutes (P<0.05). LH at 30 minutes had a similar diagnostic value to LH at 60 minutes (P>0.05). LH at 30 minutes was negatively correlated with BMI and BMI-Z value (P<0.05).The AUC for diagnosing CPP in normal weight, overweight, and obese girls at 30 minutes LH was 0.952, 0.965, and 0.954, respectively (P<0.05). CONCLUSIONS: The 30-minute GnRH stimulation test has a good value in the diagnosis of CPP in girls with different levels of BMI and is expected to replace the traditional GnRH stimulation test, but the influence of BMI on LH level should be taken seriously.

Discovery of baicalein derivatives as novel inhibitors against human pancreatic lipase: Structure-activity relationships and inhibitory mechanisms.

Human pancreatic lipase (hPL) is a vital digestive enzyme responsible for breaking down dietary fats in humans, inhibiting hPL is a feasible strategy for preventing and treating obesity. This study aims to investigate the structure-activity relationships (SARs) of flavonoids as hPL inhibitors, and to find potent hPL inhibitors from natural and synthetic flavonoids. In this work, the anti-hPL effects of forty-nine structurally diverse naturally occurring flavonoids were assessed and the SARs were summarized. The results demonstrated that the pyrogallol group on the A ring was a key moiety for hPL inhibition. Subsequently, a series of baicalein derivatives were synthesized, while 4'-amino baicalein (ABA) and 4'-pyrrolidine baicalein (PBA) were identified as novel potent hPL inhibitors (IC50 < 1 µM). Further investigations showed that scutellarein, ABA and PBA potently inhibited hPL in a non-competitive manner (Ki < 1 µM). Among all tested flavonoids, PBA showed the most potent anti-hPL effect in vitro, while this agent also exhibited favorable safety profiles, unique tissue distribution (high exposure level to intestinal system but low exposure levels to deep organs) and impressive in vivo effects for lowering blood triglyceride levels in mice. Collectively, this work uncovers the SARs of flavonoids against hPL, while a newly synthetic flavonoid (PBA) emerges as a potent hPL inhibitor with favorable safety profiles and impressive anti-hPL effects in vivo.

Silencing LINC00987 ameliorates adriamycin resistance of acute myeloid leukemia via miR-4458/HMGA2 axis.

BACKGROUND: Most patients with acute myeloid leukemia (AML) eventually develop drug resistance, leading to a poor prognosis. Dysregulated long gene non coding RNAs (lincRNAs) have been implicated in chemoresistance in AML. Unfortunately, the effects of lincRNAs which participate in regulating the Adriamycin (ADR) resistance in AML cells remain unclear. Thus, the purpose of this study is to determine LINC00987 function in ADR-resistant AML. METHODS: In this study, ADR-resistant cells were constructed. LINC00987, miRNAs, and HMGA2 mRNA expression were measured by qRT-PCR. P-GP, BCRP, and HMGA2 protein were measured by Western blot. The proliferation was analyzed by MTS and calculated IC50. Soft agar colony formation assay and TUNEL staining were used to analyze cell colony formation and apoptosis. Xenograft tumor experiment was used to analyze the xenograft tumor growth of ADR-resistant AML. RESULTS: We found that higher expression of LINC00987 was observed in AML patients and associated with poor overall survival in AML patients. LINC00987 expression was increased in ADR-resistant AML cells, including ADR/MOLM13 and ADR/HL-60 cells. LINC00987 downregulation reduces ADR resistance in ADR/MOLM13 and ADR/HL-60 cells in vitro and in vivo, while LINC00987 overexpression enhanced ADR resistance in MOLM13 and HL-60 cells. Additionally, LINC00987 functions as a competing endogenous RNA for miR-4458 to affect ADR resistance in ADR/MOLM13 and ADR/HL-60 cells. HMGA2 is a target of miR-4458. LINC00987 knockdown and miR-4458 overexpression reduced HMGA2 expression. HMGA2 overexpression enhanced ADR resistance, which reversed the function of LINC00987 silencing in suppressing ADR resistance of ADR/MOLM13 and ADR/HL-60 cells. CONCLUSIONS: Downregulation of LINC00987 weakens ADR resistance by releasing miR-4458 to deplete HMGA2 in ADR/MOLM13 and ADR/HL-60. Therefore, LINC00987 may act as the therapeutic target for treating chemoresistant AML.

METTL3-mediated pre-miR-665/DLX3 m6A methylation facilitates the committed differentiation of stem cells from apical papilla.

Methyltransferase-like 3 (METTL3) is a crucial element of N6-methyladenosine (m6A) modifications and has been extensively studied for its involvement in diverse biological and pathological processes. In this study, we explored how METTL3 affects the differentiation of stem cells from the apical papilla (SCAPs) into odonto/osteoblastic lineages through gain- and loss-of-function experiments. The m6A modification levels were assessed using m6A dot blot and activity quantification experiments. In addition, we employed Me-RIP microarray experiments to identify specific targets modified by METTL3. Furthermore, we elucidated the molecular mechanism underlying METTL3 function through dual-luciferase reporter gene experiments and rescue experiments. Our findings indicated that METTL3+/- mice exhibited significant root dysplasia and increased bone loss. The m6A level and odonto/osteoblastic differentiation capacity were affected by the overexpression or inhibition of METTL3. This effect was attributed to the acceleration of pre-miR-665 degradation by METTL3-mediated m6A methylation in cooperation with the "reader" protein YTHDF2. Additionally, the targeting of distal-less homeobox 3 (DLX3) by miR-665 and the potential direct regulation of DLX3 expression by METTL3, mediated by the "reader" protein YTHDF1, were demonstrated. Overall, the METTL3/pre-miR-665/DLX3 pathway might provide a new target for SCAP-based tooth root/maxillofacial bone tissue regeneration.

Refining the phylogeny and taxonomy of the apple tribe Maleae (Rosaceae): insights from phylogenomic analyses of 563 plastomes and a taxonomic synopsis of Photinia and its allies in the Old World.

This study addresses the longstanding absence of a comprehensive phylogenetic backbone for the apple tribe Maleae, a deficiency attributed to limited taxon and marker sampling. We conducted an extensive taxon sampling, incorporating 563 plastomes from a diverse range of 370 species encompassing 26 presently recognized genera. Employing a range of phylogenetic inference methods, including RAxML and IQ-TREE2 for Maximum Likelihood (ML) analyses, we established a robust phylogenetic framework for the Maleae tribe. Our phylogenomic investigations provided compelling support for three major clades within Maleae. By integrating nuclear phylogenetic data with morphological and chromosomal evidence, we propose an updated infra-tribal taxonomic system, comprising subtribe Malinae Reveal, subtribe Lindleyinae Reveal, and subtribe Vauqueliniinae B.B.Liu (subtr. nov.). Plastid phylogenetic analysis also confirmed the monophyly of most genera, except for Amelanchier, Malus, Sorbus sensu lato, and Stranvaesia. In addition, we present a comprehensive taxonomic synopsis of Photinia and its morphological allies in the Old World, recognizing 27 species and ten varieties within Photinia, three species and two varieties within Stranvaesia, and two species and three varieties within Weniomeles. Furthermore, we also lectotypified 12 names and made two new combinations, Photiniamicrophylla (J.E.Vidal) B.B.Liu and Weniomelesatropurpurea (P.L.Chiu ex Z.H.Chen & X.F.Jin) B.B.Liu.

Inorganic Composition Modulation of Solid Electrolyte Interphase for Fast Charging Lithium Metal Batteries.

The solid electrolyte interphase (SEI) with lithium fluoride (LiF) is critical to the performance of lithium metal batteries (LMBs) due to its high stability and mechanical properties. However, the low Li ion conductivity of LiF impedes the rapid diffusion of Li ions in the SEI, which leads to localized Li ion oversaturation dendritic deposition and hinders the practical applications of LMBs at high-current regions (>3 C). To address this issue, a fluorophosphated SEI rich with fast ion-diffusing inorganic grain boundaries (LiF/Li3P) is introduced. By utilizing a sol electrolyte that contains highly dispersed porous LiF nanoparticles modified with phosphorus-containing functional groups, a fluorophosphated SEI is constructed and the presence of electrochemically active Li within these fast ion-diffusing grain boundaries (GBs-Li) that are non-nucleated is demonstrated, ensuring the stability of the Li || NCM811 cell for over 1000 cycles at fast-charging rates of 5 C (11 mA cm-2). Additionally, a practical, long cycling, and intrinsically safe LMB pouch cell with high energy density (400 Wh kg-1) is fabricated. The work reveals how SEI components and structure design can enable fast-charging LMBs.

Activation of Einstein-Podolsky-Rosen steering sharing with unsharp nonlocal measurements.

Einstein-Podolsky-Rosen (EPR) steering is commonly shared among multiple observers by utilizing unsharp measurements. Nevertheless, their usage is restricted to local measurements and does not encompass all nonlocal measurement-based cases. In this work, a method for finding beneficial local measurement settings has been expanded to include nonlocal measurement cases. This method is applicable for any bipartite state and offers benefits even in scenarios with a high number of measurement settings. Using the Greenberger-Horne-Zeilinger state as an illustration, we show that employing unsharp nonlocal measurements can activate the phenomenon of steering sharing in contrast to using local measurements. Furthermore, our findings demonstrate that nonlocal measurements with unequal strength possess a greater activation capability compared to those with equal strength. Our activation method generates fresh concepts for conservation and recycling quantum resources.

Genome-wide CNV analysis reveals candidate genes associated with milk production traits in water buffalo (Bubalus bubalis).

Buffaloes are vital contributors to the global dairy industry. Understanding the genetic basis of milk production traits in buffalo populations is essential for breeding programs and improving productivity. In this study, we conducted whole-genome resequencing on 387 buffalo genomes from 29 diverse Asian breeds, including 132 river buffaloes, 129 swamp buffaloes, and 126 crossbred buffaloes. We identified 36,548 copy number variant (CNVs) spanning 133.29 Mb of the buffalo genome, resulting in 2,100 copy number variant regions (CNVRs), with 1,993 shared CNVRs being found within the studied buffalo types. Analyzing CNVRs highlighted distinct genetic differentiation between river and swamp buffalo subspecies, verified by evolutionary tree and principal component analyses. Admixture analysis grouped buffaloes into river and swamp categories, with crossbred buffaloes displaying mixed ancestry. To identify candidate genes associated with milk production traits, we employed 3 approaches. First, we used Vst-based population differentiation, revealing 11 genes within CNVRs that exhibited significant divergence between different buffalo breeds, including genes linked to milk production traits. Second, expression quantitative loci (eQTL) analysis revealed differential expression of CNVR-driven genes (DECGs) associated with milk production traits. Notably, known milk production-related genes were among these DECGs, validating their relevance. Last, a genome-wide association study (GWAS) identified 3 CNVRs significantly linked to peak milk yield. Our study provides comprehensive genomic insights into buffalo populations and identifies candidate genes associated with milk production traits. These findings facilitate genetic breeding programs aimed at increasing milk yield and improving quality in this economically important livestock species.

The rise of baobab trees in Madagascar.

The baobab trees (genus Adansonia) have attracted tremendous attention because of their striking shape and distinctive relationships with fauna1. These spectacular trees have also influenced human culture, inspiring innumerable arts, folklore and traditions. Here we sequenced genomes of all eight extant baobab species and argue that Madagascar should be considered the centre of origin for the extant lineages, a key issue in their evolutionary history2,3. Integrated genomic and ecological analyses revealed the reticulate evolution of baobabs, which eventually led to the species diversity seen today. Past population dynamics of Malagasy baobabs may have been influenced by both interspecific competition and the geological history of the island, especially changes in local sea levels. We propose that further attention should be paid to the conservation status of Malagasy baobabs, especially of Adansonia suarezensis and Adansonia grandidieri, and that intensive monitoring of populations of Adansonia za is required, given its propensity for negatively impacting the critically endangered Adansonia perrieri.

Triterpene esters of cirsium setosum and their anti-inflammatory activity.

Two new triterpene fatty acid esters, 3ß-palmityloxy-12,27-cyclofriedoolean-14-en-11α-ol (1) and 3ß-palmityloxy-19α-hydroxyursane (2), together with 3ß-hydroxy-11-oxo-olean-12-enyl palmitate (3) were isolated from the potent anti-inflammatory active fraction of the petroleum ether-soluble part of Cirsium setosum ethanol extract. Compound 1 was found to be a rare 12,27-cyclopropane triterpenoid. Their structures were determined through spectral data analysis combined with literature reports. Furthermore, in vitro experiment, compounds 1-3 exhibited significant inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages.

Co-pyrolysis of sewage sludge and phosphate tailings: Synergistically enhancing heavy metal immobilization and phosphorus availability.

Phosphate tailings (PT) was used to reduce the release of heavy metals (HMs) during pyrolysis and the leachable rate of residual HMs, and simultaneously improve the bioavailability of phosphorus in the sludge-based biochar. The concentration of heavy metals and the fractions determined by BCR method was used to investigate the release and the transformation of Zn, Pb, Mn, Ni and Cu during pyrolysis involved with the effects of temperature and the addition of PT. The respective pyrolysis experiments shows that the release of Zn and Pb increases with temperature for both sewage sludge (SS) and PT, and the bioavailable fractions (F1 + F2) of Mn, Ni, and Cu increases with temperature for PT. During co-pyrolysis, blended samples released lower quantities of Zn and Pb and presented lower bioavailability of HMs than the individual SS or PT. A synergistic effect of co-pyrolysis was evident for volatile Zn and Pb. The decomposition of CaMg (CO3)2 from PT produced CaO, by which the volatile ZnCl2 and PbCl2 were transformed into ZnO and PbO with less volatility and higher reactivity with SiO2 and Al2O3 than the chlorides. Then SiO2 and Al2O3 from SS acted as the final stabilizer to immobilize the oxides. The final product combined with SiO2 and Al2O3, such as ZnSiO4 and ZnAl2O4, were detected. The addition of PT also introduced more Ca and P into sludge to produce biochar with higher concentration of apatite phosphorus with higher bioavailability.

Case report: Envafolimab causes local skin necrosis.

Envafolimab is a Chinese domestic innovative fusion of a humanized single-domain programmed death-ligand 1 (PD-L1) antibody (dAb) and human immunoglobulin IgG1 crystalline fragment (Fc) developed for subcutaneous injections. It was granted conditional market authorization by the China National Medical Product Administration (NMPA) in December 2021. Envafolimab is used to treat adult patients with previously treated microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) advanced solid tumors, including patients with advanced colorectal cancer disease progression who were previously administered fluorouracil, oxaliplatin, and irinotecan, as well as other patients with advanced solid tumors who experienced disease progression after receiving standard treatment and had no other alternative treatment options. However, the lack of post-marketing clinical trial data requires conducting more clinical studies on the safety and efficacy of envafolimab in order to provide scientific basis and a reference for future therapeutic applications. In this paper, we report a case of severe skin necrosis and bleeding in the area of injection after subcutaneous administration of envafolimab in a patient diagnosed with hepatocellular carcinoma. We discuss issues that must be considered before administration of a PD-L1 inhibitor subcutaneously, which could induce immune mechanisms leading to skin necrosis in the area of injection.

Repetitive transcranial magnetic stimulation for Alzheimer's disease: an overview of systematic reviews and meta-analysis.

Objective: Alzheimer's disease (AD) is a prevalent neurodegenerative condition that significantly impacts both individuals and society. This study aims to evaluate the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a treatment for AD by summarizing the evidence from systematic reviews (SRs) and meta-analyses (MAs). Methods: SRs/MAs of rTMS for AD were collected by searching Embase, Web of Science, Cochrane Library, PubMed, CNKI, VIP, Sino-Med, and Wanfang databases. The search was conducted from database creation to January 23, 2024. Methodological quality, reporting quality and risk of bias were assessed using the Assessing Methodological Quality of Systematic Reviews 2 (AMSTAR-2), Risk of Bias in Systematic Reviews (ROBIS) tool and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). In addition, the quality of evidence for outcome measures was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE). Results: Eight SRs/MAs included in this study met the inclusion criteria. Based on the AMSTAR-2, 4 of the SRs/MA were classified as low quality, while the remaining 4 were deemed to be of very low quality. The PRISMA analysis revealed that out of the 27 items reporting, 16 achieved full reporting (100%). However, there were still some deficiencies in reporting, particularly related to protocol and registration, search strategy, risk of bias, and additional analysis. The ROBIS tool indicated that only 3 SRs/MAs had a low risk of bias. The GRADE assessment indicated that 6 outcomes were of moderate quality (18.75%), 16 were of low quality (50%), and 10 were classified as very low quality (31.25%). Conclusion: Based on the evidence collected, rTMS appears to be effective in improving cognitive function in AD patients, although the methodological quality of the SRs/MAs reduces the reliability of the conclusions and the overall quality is low. However, based on the available results, we still support the value of rTMS as an intervention to improve cognitive function in AD. In future studies, it is necessary to confirm the efficacy of rTMS in AD patients and provide more reliable and scientific data to contribute to evidence-based medicine.

The genomic history and global migration of a windborne pest.

Many insect pests, including the brown planthopper (BPH), undergo windborne migration that is challenging to observe and track. It remains controversial about their migration patterns and largely unknown regarding the underlying genetic basis. By analyzing 360 whole genomes from around the globe, we clarify the genetic sources of worldwide BPHs and illuminate a landscape of BPH migration showing that East Asian populations perform closed-circuit journeys between Indochina and the Far East, while populations of Malay Archipelago and South Asia undergo one-way migration to Indochina. We further find round-trip migration accelerates population differentiation, with highly diverged regions enriching in a gene desert chromosome that is simultaneously the speciation hotspot between BPH and related species. This study not only shows the power of applying genomic approaches to demystify the migration in windborne migrants but also enhances our understanding of how seasonal movements affect speciation and evolution in insects.