Design, Synthesis, Bioactivity, and Tentative Exploration of Action Mode for Benzyl Ester-Containing Derivatives.

The active splicing strategy has witnessed improvement in bioactivity and antifungal spectra in pesticide discovery. Herein, a series of simple-structured molecules (Y1-Y53) containing chloro-substituted benzyl esters were designed using the above strategy. The structure-activity relationship (SAR) analysis demonstrated that the fatty acid fragment-structured esters were more effective than those containing an aromatic acid moiety or naphthenic acid part. Compounds Y36 and Y41, which featured a thiazole-4-acid moiety and trifluoromethyl aliphatic acid part, respectively, exhibited excellent in vivo curative activity (89.4%, 100 mg/L Y36) and in vitro fungicidal activity (EC50 = 0.708 mg/L, Y41) against Botrytis cinerea. Determination of antifungal spectra and analysis of scanning electron microscopy (SEM), membrane permeability, cell peroxidation, ergosterol content, oxalic acid pathways, and enzymatic assays were performed separately here. Compound Y41 is cost effective due to its simple structure and shows promise as a disease control candidate. In addition, Y41 might act on a novel target through a new pathway that disrupts the cell membrane integrity by inducing cell peroxidation.

F wave analysis based on the compound muscle action potential scan.

INTRODUCTION/AIMS: Conventional F wave analysis involves a relatively uniform physiological environment induced by supramaximal stimulations. The F wave characteristics in a dynamic physiological condition, however, are rarely investigated. This study aimed to improve understanding of F wave properties in the more dynamic process by introducing a novel method to analyze F waves based on the compound muscle action potential (CMAP) scan technique. METHODS: Twenty four healthy subjects participated in the study. The CMAP scan was applied to record muscle responses in the abductor pollicis brevis (APB) and abductor digiti minimi (ADM) muscles, respectively. F wave characteristics including mean F wave amplitude and latency (F-M latency), persistence and activating threshold were quantified. RESULTS: An average of 200 F waves per muscle were obtained from the CMAP scan recording. Weak to moderate correlations between F wave amplitude and stimulating intensity were observed in most of the APB (19 muscles; r = 0.33 ± 0.14, all p < .05) and ADM (23 muscles, r = 0.46 ± 0.16, all p < .05) muscles. Significantly longer mean F latency and lower activating F-threshold were found in the ADM muscles (F-M latency: APB: 25.43 ± 2.39 ms, ADM: 26.15 ± 2.32 ms, p < .05; F-threshold: APB: 7.68 ± 8.96% CMAP, ADM: 2.35 ± 2.42% CMAP, p < .05). DISCUSSION: This study introduces new features of F waves using the CMAP scan technique and identifies differences of F wave characteristics between the hand muscles. The CMAP scan based F waves analysis can be combined with the motor unit number estimation to assess functional alterations in motor neurons in neurological disorders.

High Density 3D Carbon Tube Nanoarray Electrode Boosting the Capacitance of Filter Capacitor.

Electric double-layer capacitors (EDLCs) with fast frequency response are regarded as small-scale alternatives to the commercial bulky aluminum electrolytic capacitors. Creating carbon-based nanoarray electrodes with precise alignment and smooth ion channels is crucial for enhancing EDLCs' performance. However, controlling the density of macropore-dominated nanoarray electrodes poses challenges in boosting the capacitance of line-filtering EDLCs. Herein, a simple technique to finely adjust the vertical-pore diameter and inter-spacing in three-dimensional nanoporous anodic aluminum oxide (3D-AAO) template is achieved, and 3D compactly arranged carbon tube (3D-CACT) nanoarrays are created as electrodes for symmetrical EDLCs using nanoporous 3D-AAO template-assisted chemical vapor deposition of carbon. The 3D-CACT electrodes demonstrate a high surface area of 253.0 m2 g-1, a D/G band intensity ratio of 0.94, and a C/O atomic ratio of 8. As a result, the high-density 3D-CT nanoarray-based sandwich-type EDLCs demonstrate a record high specific areal capacitance of 3.23 mF cm-2 at 120 Hz and exceptional fast frequency response due to the vertically aligned and highly ordered nanoarray of closely packed CT units. The 3D-CT nanoarray electrode-based EDLCs could serve as line filters in integrated circuits, aiding power system miniaturization.

Association between low handgrip strength and incontinence among Chinese middle-aged and older people: A cross-sectional study.

Objective: Incontinence seriously affects the lives of middle-aged and older people. Pelvic floor muscle assessment is very important for incontinence, and handgrip strength can be used as an auxiliary diagnostic tool. Our study aims to find new cutoff points of handgrip strength as early indicators of incontinence and analyze the association between low handgrip strength and incontinence among Chinese middle-aged and older people. Methods: Participants were recruited from the 2015 China Health and Retirement Longevity Study. Receiver operating characteristic (ROC) curves were used to find the handgrip strength cutoff point. Logistic regression analysis was performed to explore other incontinence-related risk factors. Results: The study included 10,229 middle-aged and older people. Compared with normal handgrip strength participants, medium strength participants had 1.510 [men, 95% confidence interval (CI) = 1.017-2.243] and 1.792 (women, 95% CI = 1.294-2.480) times greater risk of incontinence, and low strength participants had 2.420 (men, 95% CI = 1.787-3.277) and 1.516 (women, 95% CI = 1.130-2.032) times greater risk of incontinence. Trend test results showed that the risk of incontinence increased with decreasing handgrip strength in middle-aged and older people. Conclusions: Our study suggests that handgrip strength < 31 kg in men and < 20.5 kg in women is significantly associated with higher risk of incontinence in Chinese middle-aged and older people. The risk of incontinence increases with decreasing handgrip strength. Handgrip strength should be measured in routine physical examinations in middle-aged and older people for timely assessment and intervention in incontinence.

Mauritone A, a new polyketide from a fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532.

A new polyketide, mauritone A (1) with six known polyketides curvulone B (2), curvularin (3), 12-oxocurvularin (4), (10E,15S)-10,11-dehydrocurvularin (5), (11R,15S)-11-hydroxycurvularin (6), and (11S,15S)-11-hydroxycurvularin (7) were isolated from the fungal-bacterial symbiont Aspergillus spelaeus GXIMD 04541/Sphingomonas echinoides GXIMD 04532 derived from Mauritia arabica. Their structures were elucidated by extensive spectral analysis. All compounds (1-7) were evaluated for their anti-inflammatory effects. The inhibitory effects of 4, 5, and 7 on nitric oxide (NO) production were found to be significant, with IC50 values of 5.5 ± 0.26, 2.0 ± 0.31, and 8.3 ± 0.62 µM, respectively, surpassing that of the positive control quercetin (10.6 ± 0.64 µM). Compounds 3 and 6 exhibited moderate inhibition of NO, with IC50 values of 18.6 ± 0.53 and 12.7 ± 0.45 µM, respectively.

Hainanenin-1, an oncolytic peptide, triggers immunogenic cell death via STING activation in triple-negative breast cancer.

BACKGROUND: In triple-negative breast cancer (TNBC) therapy, insufficient tumor infiltration by lymphocytes significantly hinders the efficacy of immune checkpoint inhibitors. We have previously demonstrated that Hainanenin-1 (HN-1), a host defense peptide (HDP) identified from Hainan frog skin, induces breast cancer apoptosis and boots anti-tumor immunity via unknown mechanism. METHODS: We used in vitro experiments to observe immunogenic cell death (ICD) indicators in HN-1-treated TNBC cell lines, a mouse tumor model to verify HN-1 promotion of mice anti-tumor immune response, and an in vitro drug sensitivity test of patient-derived breast cancer cells to verify the inhibitory effect of HN-1. RESULTS: HN-1 induced ICD in TNBC in a process during which damage-associated molecular patterns (DAMPs) were released that could further increase the anti-tumor immune response. The secretion level of interleukin 2 (IL-2), IL-12, and interferon γ in the co-culture supernatant was increased, and dendritic cells (DCs) were activated via a co-culture with HN-1-pretreated TNBC cells. As a result, HN-1 increased the infiltration of anti-tumor immune cells (DCs and T lymphocytes) in the mouse model bearing both 4T1 and EMT6 tumors. Meanwhile, regulatory T cells and myeloid-derived suppressor cells were suppressed. In addition, HN-1 induced DNA damage, and double-strand DNA release in the cytosol was significantly enhanced, indicating that HN-1 might stimulate ICD via activation of STING pathway. The knockdown of STING inhibited HN-1-induced ICD. Of note, HN-1 exhibited inhibitory effects on patient-derived breast cancer cells under three-dimensional culture conditions. CONCLUSIONS: Collectively, our study demonstrated that HN-1 could be utilized as a potential compound that might augment immunotherapy effects in patients with TNBC.

Cyclosporine A protects podocytes by regulating transgelin in adriamycin-induced podocyte injury.

INTRODUCTION: The calcineurin inhibitor cyclosporine A (CsA) has been shown to effectively reduce proteinuria. However, its precise mechanism is still not fully understood. Our previous study showed that CsA reduced proteinuria by directly stabilizing the foot process (FP) cytoskeletal structure via cofilin-1, suggesting that synaptopodin, a podocyte-specific actin protein, is not the sole target of CsA in podocytes. METHODS: In this study, we established an adriamycin (ADR)-induced nephropathy rat model and a cultured podocyte injury model. We employed Western blotting and immunofluorescence techniques to assess the expression and distribution of transgelin, KLF-4, nephrin, and synaptopodin. RESULTS: We observed a significant increase in proteinuria levels accompanied by loss of normal FP structure in the ADR-induced nephropathy rat model. The levels of the actin cross-linking protein transgelin were increased significantly, while those of the podocyte-specific molecules nephrin and synaptopodin were decreased in vivo. Treatment with CsA effectively reduced proteinuria while restoring FP effacement stability in ADR-induced nephropathy models, and restoring the expression of transgelin, nephrin, and synaptopodin both in vivo and in vitro. Furthermore, CsA treatment dose-dependently decreased transgelin levels while significantly increasing KLF-4 expression in injured podocytes. In addition, CsA failed to downregulate transgelin when KLF-4 was specifically knocked down. CONCLUSION: Our findings suggest that CsA protects against podocyte injury by downregulating abnormally high levels of transgelin via upregulation of KLF-4 expression.

High expression of RUNX1 in colorectal cancer subtype accelerates malignancy by inhibiting HMGCR.

Colorectal cancer (CRC) presents a complex landscape, characterized by both inter-tumor and intra-tumor heterogeneity. RUNX1, a gene implicated in modulating tumor cell growth, survival, and differentiation, remains incompletely understood regarding its impact on CRC prognosis. In our investigation, we discerned a positive correlation between elevated RUNX1 expression and aggressive phenotypes across various CRC subtypes. Notably, knockdown of RUNX1 demonstrated efficacy in restraining CRC proliferation both in vitro and in vivo, primarily through inducing apoptosis and impeding cell proliferation. Mechanistically, we unveiled a direct regulatory link between RUNX1 and cholesterol synthesis, mediated by its control over HMGCR expression. Knockdown of RUNX1 in CRC cells triggered HMGCR transcriptional activation, culminating in elevated cholesterol levels that subsequently hindered cancer progression. Clinically, heightened RUNX1 expression emerged as a prognostic marker for adverse outcomes in CRC patients. Our findings underscore the pivotal involvement of RUNX1 in CRC advancement and its potential as a therapeutic target. The unique influence of RUNX1 on cholesterol synthesis and HMGCR transcriptional regulation uncovers a novel pathway contributing to CRC progression.

Single immunization of non-adjuvanted recombinant TTFC-mi3 nanoparticle vaccine elicited a rapid and potent protective immunity against tetanus.

The conventional inactivated tetanus toxin plays an instrumental role in preventing tetanus. Nevertheless, the challenges associated with its production process, the potential for adverse reactions, and reduced effectiveness in vulnerable populations such as neonates and the elderly rise the need for a novel tetanus toxin vaccine. Recombinant subunit vaccine offer a viable solution, and the tetanus toxin fragment C (TTFC) is emerging as a promising candidate. In this study, through spontaneous isopeptide bond formation we conjugated the recombinant TTFC to self-assembled mi3 nanoparticle, which derived from an optimized KDPG aldolase, and generated the TTFC-mi3 protein nanoparticle vaccine. We found that TTFC-mi3 is stable, uniform spherical nanoparticles. Comparing with the free TTFC alone, TTFC-mi3 enhances the uptake and subsequent activation of dendric cells (DCs). In addition, a single dose of adjuvant-free TTFC-mi3 elicited a more rapid and potent protective immunity in mice. Moreover, TTFC-mi3 is of favorable safety in vitro and in vivo. Our findings indicate that TTFC-mi3 is a rapid-response, non-aluminum-adjuvanted vaccine against tetanus.

Cytology, metabolomics, and proteomics reveal the grain filling process and quality difference of wheat.

Comparative proteomics and non-target metabolomics, together with physiological and microstructural analyses of wheat grains (at 15, 20, 25, and 30 days after anthesis) from two different quality wheat varieties (Gaoyou 5766 (strong-gluten) and Zhoumai 18) were performed to illustrate the grain filling material dynamics and to search for quality control genes. The differential expressions of 1541 proteins and 406 metabolites were found. They were mostly engaged in protein metabolism, stress/defense, energy metabolism, and amino acid metabolism, and the metabolism of stored proteins and carbohydrates was the major focus of the latter stages. The core proteins and metabolites in the growth process were identified, and the candidate genes for quality differences were screened. In conclusion, this study offers a molecular explanation for the establishment of wheat quality, and it aids in our understanding of the intricate metabolic network between different qualities of wheat at the filling stage.

Molecular structural modification of myofibrillar protein from oyster (Crassostrea gigas) with oligosaccharides for improving its gel properties.

Glycation is a promising approach to enhance protein gel characteristics in the food industry. The impact of oyster myofibrillar protein (MP) being glycosylated with six oligosaccharides (dextran [Dex]-1 kDa, 5 kDa, 6 kDa, and 10 kDa, xylan [Xyla], and xyloglucan [Xyg]) on structural properties, aggregation behavior and gel properties was investigated in this study. The findings demonstrated that oligosaccharides significantly increased the glycation degree of MP by forming a stable tertiary conformation, increasing the contents of the disulfide bond and hydrogen bonds. Additionally, particle sizes decreased and solubility increased after glycation, improving the gel's strength, water-holding capacity, thermal stability, elastic modulus, and ordered network layout. It was determined that MP-Dex 5 had the best gel properties. The gel strength and water holding capacity of MP-Dex 5 increased by 70.59% and 32.27%, respectively. Molecular dynamics simulations results showed van der Waals energy and electrostatic interactions favor myosin binding to Dex or Xyla units. This study will provide insights into the relationship between molecular structure, aggregation behavior and gel property of oyster MP-oligosaccharide couples, and expand the application of oyster MP in food gels.

Unveiling the Roles of Alloyed Boron in Hexavalent Chromium Removal Using Borohydride-Synthesized Nanoscale Zerovalent Iron: Electron Donor and Antipassivator.

Nanoscale zerovalent iron synthesized using borohydride (B-NZVI) has been widely applied in environmental remediation in recent decades. However, the contribution of boron in enhancing the inherent reactivity of B-NZVI and its effectiveness in removing hexavalent chromium [Cr(VI)] have not been well recognized and quantified. To the best of our knowledge, herein, a core-shell structure of B-NZVI featuring an Fe-B alloy shell beneath the iron oxide shell is demonstrated for the first time. Alloyed boron can reduce H+, contributing to more than 35.6% of H2 generation during acid digestion of B-NZVIs. In addition, alloyed B provides electrons for Fe3+ reduction during Cr(VI) removal, preventing in situ passivation of the reactive particle surface. Meanwhile, the amorphous oxide shell of B-NZVI exhibits an increased defect density, promoting the release of Fe2+ outside the shell to reduce Cr(VI), forming layer-structured precipitates and intense Fe-O bonds. Consequently, the surface-area-normalized capacity and surface reaction rate of B-NZVI are 6.5 and 6.9 times higher than those of crystalline NZVI, respectively. This study reveals the importance of alloyed B in Cr(VI) removal using B-NZVI and presents a comprehensive approach for investigating electron pathways and mechanisms involved in B-NZVIs for contaminant removal.

A High-Performance Passive Radiative Cooling Metafabric with Janus Wettability and Thermal Conduction.

With the development of industry and global warming, passive radiative cooling textiles have recently drawn great interest owing to saving energy consumption and preventing heat-related illnesses. Nevertheless, existing cooling textiles often lack efficient sweat management capacity and wearable comfort under many practical conditions. Herein, a hierarchical cooling metafabric that integrates passive radiation, thermal conduction, sweat evaporation, and excellent wearable comfort is reported through an electrospinning strategy. The metafabric presents excellent solar reflectivity (99.7%, 0.3-2.5 µm) and selective infrared radiation (92.4%, 8-13 µm), given that the unique optical nature of materials and wettability gradient/micro-nano hierarchical structure design. The strong moisture-wicking effect (water vapor transmission (WVT) of 2985 g m-2 d-1 and directional water transport index (R) of 1029.8%) and high heat-conduction capacity can synergistically enhance the radiative cooling efficiency of the metafabric. The outdoor experiment reveals that the metafabric can obtain cooling temperatures of 13.8 °C and 19.3 °C in the dry and sweating state, respectively. Meanwhile, the metafabric saves ≈19.3% of annual energy consumption compared with the buildings with HAVC systems in Shanghai. The metafabric also demonstrates desirable breathability, mechanical strength, and washability. The cost-effective and high-performance metafabric may offer a novel avenue for developing next-generation personal cooling textiles.

Polystyrene Nanoplastics Induce Lipid Metabolism Disorder by Activating the PERK-ATF4 Signaling Pathway in Mice.

In recent years, the study of microplastics (MPs) and nanoplastics (NPs) and their effects on human health has gained significant attention. The impacts of NPs on lipid metabolism and the specific mechanisms involved remain poorly understood. To address this, we utilized high-throughput sequencing and molecular biology techniques to investigate how endoplasmic reticulum (ER) stress might affect hepatic lipid metabolism in the presence of polystyrene nanoplastics (PS-NPs). Our findings suggest that PS-NPs activate the PERK-ATF4 signaling pathway, which in turn upregulates the expression of genes related to lipid synthesis via the ATF4-PPARγ/SREBP-1 pathway. This activation leads to an abnormal accumulation of lipid droplets in the liver. 4-PBA, a known ER stress inhibitor, was found to mitigate the PS-NPs-induced lipid metabolism disorder. These results demonstrate the hepatotoxic effects of PS-NPs and clarify the mechanisms of abnormal lipid metabolism induced by PS-NPs.

Supersulfides suppress type-â and type-â ¡ interferon responses by blocking JAK/STAT signaling in macrophages.

Interferons (IFNs) are cytokines produced and secreted by immune cells when viruses, tumor cells, and so forth, invade the body. Their biological effects are diverse, including antiviral, cell growth-inhibiting, and antitumor effects. The main subclasses of interferons include type-I (e.g., IFN-α and IFN-ß) and type-II (IFN-γ), which activate intracellular signals by binding to type-I and type-II IFN receptors, respectively. We have previously shown that when macrophages are treated with supersulfide donors, which have polysulfide structures in which three or more sulfur atoms are linked within the molecules, IFN-ß-induced cellular responses, including signal transducer and activator of transcription 1 (STAT1) phosphorylation and inducible nitric oxide synthase (iNOS) expression, were strongly suppressed. However, the subfamily specificity of the suppression of IFN signals by supersulfides and the mechanism of this suppression are unknown. This study demonstrated that supersulfide donor N-acetyl-L-cysteine tetrasulfide (NAC-S2) can inhibit IFN signaling in macrophages stimulated not only with IFN-α/ß but also with IFN-γ. Our data suggest that NAC-S2 blocks phosphorylation of Janus kinases (JAKs), thereby contributes to the inhibition of phosphorylation of STAT1. Under the current experimental conditions, hydrogen sulfide (H2S) donor NaHS failed to inhibit IFN signaling. Similar to NAC-S2, carbohydrate-based supersulfide donor thioglucose tetrasulfide (TGS4) was capable of strongly inhibiting tumor necrosis factor-αproduction, iNOS expression, and nitric oxide production from macrophages stimulated with lipopolysaccharide. Further understanding of molecular mechanisms how supersulfide donors exhibit their inhibitory actions towards JAK/STAT signaling is necessary basis for development of supersulfide-based therapeutic strategy against autoimmune disorders with dysregulated IFN signaling.

Risk of major depressive increases with increasing frequency of alcohol drinking: a bidirectional two-sample Mendelian randomization analysis.

Introduction: A growing body of evidence suggests that alcohol use disorders coexist with depression. However, the causal relationship between alcohol consumption and depression remains a topic of controversy. Methods: We conducted a two-sample two-way Mendelian randomization analysis using genetic variants associated with alcohol use and major depressive disorder from a genome-wide association study. Results: Our research indicates that drinking alcohol can reduce the risk of major depression (odds ratio: 0.71, 95% confidence interval: 0.54~0.93, p = 0.01), while increasing the frequency of drinking can increase the risk of major depression (odds ratio: 1.09, 95% confidence interval: 1.00~1.18, p = 0.04). Furthermore, our multivariate MR analysis demonstrated that even after accounting for different types of drinking, the promoting effect of drinking frequency on the likelihood of developing major depression still persists (odds ratio: 1.13, 95% confidence interval: 1.04~1.23, p = 0.005). Additionally, mediation analysis using a two-step MR approach revealed that this effect is partially mediated by the adiposity index, with a mediated proportion of 37.5% (95% confidence interval: 0.22 to 0.38). Discussion: In this study, we found that alcohol consumption can alleviate major depression, while alcohol intake frequency can aggravate it.These findings have important implications for the development of prevention and intervention strategies targeting alcohol-related depression.

A panoramic view of the virosphere in three wastewater treatment plants by integrating viral-like particle-concentrated and traditional non-concentrated metagenomic approaches.

Wastewater biotreatment systems harbor a rich diversity of microorganisms, and the effectiveness of biotreatment systems largely depends on the activity of these microorganisms. Specifically, viruses play a crucial role in altering microbial behavior and metabolic processes throughout their infection phases, an aspect that has recently attracted considerable interest. Two metagenomic approaches, viral-like particle-concentrated (VPC, representing free viral-like particles) and non-concentrated (NC, representing the cellular fraction), were employed to assess their efficacy in revealing virome characteristics, including taxonomy, diversity, host interactions, lifestyle, dynamics, and functional genes across processing units of three wastewater treatment plants (WWTPs). Our findings indicate that each approach offers unique insights into the viral community and functional composition. Their combined use proved effective in elucidating WWTP viromes. We identified nearly 50,000 viral contigs, with Cressdnaviricota and Uroviricota being the predominant phyla in the VPC and NC fractions, respectively. Notably, two pathogenic viral families, Asfarviridae and Adenoviridae, were commonly found in these WWTPs. We also observed significant differences in the viromes of WWTPs processing different types of wastewater. Additionally, various phage-derived auxiliary metabolic genes (AMGs) were active at the RNA level, contributing to the metabolism of the microbial community, particularly in carbon, sulfur, and phosphorus cycling. Moreover, we identified 29 virus-carried antibiotic resistance genes (ARGs) with potential for host transfer, highlighting the role of viruses in spreading ARGs in the environment. Overall, this study provides a detailed and integrated view of the virosphere in three WWTPs through the application of VPC and NC metagenomic approaches. Our findings enhance the understanding of viral communities, offering valuable insights for optimizing the operation and regulation of wastewater treatment systems.

[Advances in Clinical Application of Cerebrospinal Fluid Circulating Tumor DNA 
in Leptomeningeal Metastasis of Non-small Cell Lung Cancer].

Leptomeningeal metastasis (LM) is a lethal complication of malignant tumors, with an incidence rate of 3%-5% among patients with non-small cell lung cancer (NSCLC). LM poses significant challenges in diagnosis, has poor prognosis, limited treatment options, and lacks standardized criteria for evaluating therapeutic efficacy, making it a difficult aspect of NSCLC management. Circulating tumor DNA (ctDNA), shed from tumor cells and carrying cancer-related information, holds significant value in precision oncology. Cerebrospinal fluid (CSF), present in the subarachnoid space of the brain, the spinal cord, and the central canal, and in direct contact with meningeal tissues, serves as the fluid medium that best reflects the genetic characteristics of LM. In recent years, CSF ctDNA has become a focal point due to its multi-omics features, playing a crucial role in the management of central nervous system (CNS) metastatic tumors. Its applications span the entire continuum of care, including aiding in diagnosis, assessing treatment response, predicting prognosis, and analyzing resistance mechanisms. This article provides a concise overview of CSF ctDNA detection techniques and their clinical applications in patients with NSCLC-LM.
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Systematic review and meta-analysis of root morphology and canal configuration of permanent premolars using cone-beam computed tomography.

INTRODUCTION: The efficacy of root canal treatment is greatly impacted by a thorough understanding of root canal anatomy. This systematic review and meta-analysis aim to thoroughly investigate the root morphology and canal configuration (RMCC) of permanent premolars (PMs). METHODOLOGY: A comprehensive analysis was conducted following the PRISMA guidelines. Literature exploration was carried out across four electronic databases (PubMed, Embase, Cochrane, and Web of Science). The risk of bias assessment was conducted for the included studies utilizing the Anatomical Quality Assessment (AQUA) tool. Data analysis was performed utilizing SPSS and RevMAN5.3.3. The meta-analysis was applied with a 95% confidence interval to calculate odds ratios (OR). RESULTS: Among the 82 selected studies, 59 studies exhibited potential bias in domain one (objective(s) and subject characteristics), followed by domain three (methodology characterization). The majority of maxillary PM1s had either single root (46.7%) or double roots (51.9%), while three-rooted variants were uncommon (1.4%). Conversely, most other PMs exhibited a single root. In terms of canal configuration, maxillary PM1s predominantly featured double distinct canals (87.2%), with the majority of maxillary PM2s displaying either a single canal (51.4%) or double canals (48.3%). Mandibular PMs were primarily characterized by single canals, accounting for 78.3% of mandibular PM1s and 90.3% of mandibular PM2s. Subgroup analyses revealed higher incidences of single-rooted and single-canalled PMs among Asians compared to Caucasians. Additionally, women exhibited a higher incidence of single-rooted PMs, while men showed a greater frequency of double-rooted PMs. CONCLUSIONS: The comprehensive analysis indicated that maxillary PM1s predominantly possess double roots and double canals, whereas maxillary PM2s and mandibular PMs were primarily characterized by single-rooted with a single canal. Notably, single root and single canal were more prevalent among women and Asian samples.

Gasdermin D deficiency aborts myeloid calcium influx to drive granulopoiesis in lupus nephritis.

Gasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human and mouse LN kidneys, predominantly in CD11b+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.