Large-Scale Comparative Analyses of Tick Genomes Elucidate Their Genetic Diversity and Vector Capacities.

Among arthropod vectors, ticks transmit the most diverse human and animal pathogens, leading to an increasing number of new challenges worldwide. Here we sequenced and assembled high-quality genomes of six ixodid tick species and further resequenced 678 tick specimens to understand three key aspects of ticks: genetic diversity, population structure, and pathogen distribution. We explored the genetic basis common to ticks, including heme and hemoglobin digestion, iron metabolism, and reactive oxygen species, and unveiled for the first time that genetic structure and pathogen composition in different tick species are mainly shaped by ecological and geographic factors. We further identified species-specific determinants associated with different host ranges, life cycles, and distributions. The findings of this study are an invaluable resource for research and control of ticks and tick-borne diseases.

Nitrogen-dependent binding of the transcription factor PBF1 contributes to the balance of protein and carbohydrate storage in maize endosperm.

Fluctuations in nitrogen (N) availability influence protein and starch levels in maize (Zea mays) seeds, yet the underlying mechanism is not well understood. Here, we report that N limitation impacted the expression of many key genes in N and carbon (C) metabolism in the developing endosperm of maize. Notably, the promoter regions of those genes were enriched for P-box sequences, the binding motif of the transcription factor prolamin-box binding factor 1 (PBF1). Loss of PBF1 altered accumulation of starch and proteins in endosperm. Under different N conditions, PBF1 protein levels remained stable but PBF1 bound different sets of target genes, especially genes related to the biosynthesis and accumulation of N and C storage products. Upon N-starvation, the absence of PBF1 from the promoters of some zein genes coincided with their reduced expression, suggesting that PBF1 promotes zein accumulation in the endosperm. In addition, PBF1 repressed the expression of sugary1 (Su1) and starch branching enzyme 2b (Sbe2b) under normal N supply, suggesting that, under N-deficiency, PBF1 redirects the flow of C skeletons for zein toward the formation of C compounds. Overall, our study demonstrates that PBF1 modulates C and N metabolism during endosperm development in an N-dependent manner.

Tuning the Chern number in quantum anomalous Hall insulators.

A quantum anomalous Hall (QAH) state is a two-dimensional topological insulating state that has a quantized Hall resistance of h/(Ce2) and vanishing longitudinal resistance under zero magnetic field (where h is the Planck constant, e is the elementary charge, and the Chern number C is an integer)1,2. The QAH effect has been realized in magnetic topological insulators3-9 and magic-angle twisted bilayer graphene10,11. However, the QAH effect at zero magnetic field has so far been realized only for C = 1. Here we realize a well quantized QAH effect with tunable Chern number (up to C = 5) in multilayer structures consisting of alternating magnetic and undoped topological insulator layers, fabricated using molecular beam epitaxy. The Chern number of these QAH insulators is determined by the number of undoped topological insulator layers in the multilayer structure. Moreover, we demonstrate that the Chern number of a given multilayer structure can be tuned by varying either the magnetic doping concentration in the magnetic topological insulator layers or the thickness of the interior magnetic topological insulator layer. We develop a theoretical model to explain our experimental observations and establish phase diagrams for QAH insulators with high, tunable Chern number. The realization of such insulators facilitates the application of dissipationless chiral edge currents in energy-efficient electronic devices, and opens up opportunities for developing multi-channel quantum computing and higher-capacity chiral circuit interconnects.

Electrical switching of the edge current chirality in quantum anomalous Hall insulators.

A quantum anomalous Hall (QAH) insulator is a topological phase in which the interior is insulating but electrical current flows along the edges of the sample in either a clockwise or counterclockwise direction, as dictated by the spontaneous magnetization orientation. Such a chiral edge current eliminates any backscattering, giving rise to quantized Hall resistance and zero longitudinal resistance. Here we fabricate mesoscopic QAH sandwich Hall bar devices and succeed in switching the edge current chirality through thermally assisted spin-orbit torque (SOT). The well-quantized QAH states before and after SOT switching with opposite edge current chiralities are demonstrated through four- and three-terminal measurements. We show that the SOT responsible for magnetization switching can be generated by both surface and bulk carriers. Our results further our understanding of the interplay between magnetism and topological states and usher in an easy and instantaneous method to manipulate the QAH state.

Autophagy is induced by swine acute diarrhea syndrome coronavirus through the cellular IRE1-JNK-Beclin 1 signaling pathway after an interaction of viral membrane-associated papain-like protease and GRP78.

Autophagy plays an important role in the infectious processes of diverse pathogens. For instance, cellular autophagy could be harnessed by viruses to facilitate replication. However, it is still uncertain about the interplay of autophagy and swine acute diarrhea syndrome coronavirus (SADS-CoV) in cells. In this study, we reported that SADS-CoV infection could induce a complete autophagy process both in vitro and in vivo, and an inhibition of autophagy significantly decreased SADS-CoV production, thus suggesting that autophagy facilitated the replication of SADS-CoV. We found that ER stress and its downstream IRE1 pathway were indispensable in the processes of SADS-CoV-induced autophagy. We also demonstrated that IRE1-JNK-Beclin 1 signaling pathway, neither PERK-EIF2S1 nor ATF6 pathways, was essential during SADS-CoV-induced autophagy. Importantly, our work provided the first evidence that expression of SADS-CoV PLP2-TM protein induced autophagy through the IRE1-JNK-Beclin 1 signaling pathway. Furthermore, the interaction of viral PLP2-TMF451-L490 domain and substrate-binding domain of GRP78 was identified to activate the IRE1-JNK-Beclin 1 signaling pathway, and thus resulting in autophagy, and in turn, enhancing SADS-CoV replication. Collectively, these results not only showed that autophagy promoted SADS-CoV replication in cultured cells, but also revealed that the molecular mechanism underlying SADS-CoV-induced autophagy in cells.

Transcription factor ZmEREB97 regulates nitrate uptake in maize (Zea mays) roots.

Maize (Zea mays L.) has very strong requirements for nitrogen. However, the molecular mechanisms underlying the regulations of nitrogen uptake and translocation in this species are not fully understood. Here, we report that an APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factor ZmEREB97 functions as an important regulator in the N-signaling network in maize. Predominantly expressed and accumulated in main root and lateral root primordia, ZmEREB97 rapidly responded to nitrate treatment. By overlapping the analyses of differentially expressed genes and conducting a DAP-seq assay, we identified 1446 potential target genes of ZmEREB97. Among these, 764 genes were co-regulated in two lines of zmereb97 mutants. Loss of function of ZmEREB97 substantially weakened plant growth under both hydroponic and soil conditions. Physiological characterization of zmereb97 mutant plants demonstrated that reduced biomass and grain yield were both associated with reduced nitrate influx, decreased nitrate content and less N accumulation. We further demonstrated that ZmEREB97 directly targets and regulates the expression of six ZmNRT genes by binding to the GCC box-related sequences in gene promoters. Collectively, these data suggest that ZmEREB97 is a major positive regulator of the nitrate response and that it plays an important role in optimizing nitrate uptake, offering a target for improvement of nitrogen use efficiency in crops.

Cytidine diphosphate diacylglycerol synthase is essential for mitochondrial structure and energy production in Arabidopsis thaliana.

Cytidine diphosphate diacylglycerol (CDP-DAG), an important intermediate for glycerolipid biosynthesis, is synthesized under the catalytic activity of CDP-DAG synthase (CDS) to produce anionic phosphoglycerolipids such as phosphatidylglycerol (PG) and cardiolipin (CL). Previous studies showed that Arabidopsis CDSs are encoded by a small gene family, termed CDS1-CDS5, the members of which are integral membrane proteins in endoplasmic reticulum (ER) and in plastids. However, the details on how CDP-DAG is provided for mitochondrial membrane-specific phosphoglycerolipids are missing. Here we present the identification of a mitochondrion-specific CDS, designated CDS6. Enzymatic activity of CDS6 was demonstrated by the complementation of CL synthesis in the yeast CDS-deficient tam41Δ mutant. The Arabidopsis cds6 mutant lacking CDS6 activity showed decreased mitochondrial PG and CL biosynthesis capacity, a severe growth deficiency finally leading to plant death. These defects were rescued partly by complementation with CDS6 or supplementation with PG and CL. The ultrastructure of mitochondria in cds6 was abnormal, missing the structures of cristae. The degradation of triacylglycerol (TAG) in lipid droplets and starch in chloroplasts in the cds6 mutant was impaired. The expression of most differentially expressed genes involved in the mitochondrial electron transport chain was upregulated, suggesting an energy-demanding stage in cds6. Furthermore, the contents of polar glycerolipids in cds6 were dramatically altered. In addition, cds6 seedlings lost the capacity for cell proliferation and showed a higher oxidase activity. Thus, CDS6 is indispensable for the biosynthesis of PG and CL in mitochondria, which is critical for establishing mitochondrial structure, TAG degradation, energy production and seedling development.

A novel inherited CARD9 deficiency in an otherwise healthy woman with CNS candidiasis.

Patients with caspase-associated recruitment domain-9 (CARD9) deficiency are more likely to develop invasive fungal disease that affect CNS. However, the understanding of how Candida invades and persists in CNS is still limited. We here reported a 24-year-old woman who were previously immunocompetent and diagnosed with CNS candidiasis. A novel autosomal recessive homozygous CARD9 mutation (c.184 + 5G > T) from this patient was identified using whole genomic sequencing. Furthermore, we extensively characterized the impact of this CARD9 mutation on the host immune response in monocytes, neutrophils and CD4 + T cells, using single cell sequencing and in vitro experiments. Decreased pro-inflammatory cytokine productions of CD14 + monocyte, impaired Th17 cell differentiation, and defective neutrophil accumulation in CNS were found in this patient. In conclusion, this study proposed a novel mechanism of CNS candidiasis development. Patients with CNS candidiasis in absence of known immunodeficiencies should be analyzed for CARD9 gene mutation as the cause of invasive fungal infection predisposition.

Characterization of YABBY transcription factors in Osmanthus fragrans and functional analysis of OfYABBY12 in floral scent formation and leaf morphology.

BACKGROUND: The plant-specific YABBY transcription factor family plays important roles in plant growth and development, particularly leaf growth, floral organ formation, and secondary metabolite synthesis. RESULTS: Here, we identified a total of 13 OfYABBY genes from the Osmanthus fragrans genome. These 13 OfYABBY genes were divided into five subfamilies through phylogenetic analysis, and genes in the same subfamily showed similar gene structures and conserved protein motifs. Gene duplication promoted the expansion of the OfYABBY family in O. fragrans. Tissue-specific expression analysis showed that the OfYABBY family was mainly expressed in O. fragrans leaves and floral organs. To better understand the role of OfYABBY genes in plant growth and development, OfYABBY12 was selected for heterologous stable overexpression in tobacco, and OfYABBY12-overexpressing tobacco leaves released significantly fewer volatile organic compounds than wild-type tobacco leaves. Overexpression of OfYABBY12 led to the downregulation of NtCCD1/4 and decreased ß-ionone biosynthesis. Correspondingly, a dual-luciferase assay showed that OfYABBY12 negatively regulated the expression of OfCCD4, which promotes ß-ionone synthesis. Furthermore, tobacco leaves overexpressing OfYABBY12 were curled and wrinkled and had significantly reduced leaf thickness and leaf inclusions and significantly extended flower pistils (styles). CONCLUSION: Overall, the results suggest that the OfYABBY gene family may influence the biosynthesis of the floral scent (especially ß-ionone) in O. fragrans and may regulate leaf morphogenesis and lateral organs.

Precise Tuning of Bilayer Ultrasmall MoS2 Featuring Inhibition of Carrier Recombination and Fast Surface Chemistry for Green H2 Evolution.

Achieving water splitting to produce green H2 , using the noble-metal-free MoS2 , has attracted huge interest from researchers. However, tuning the number of MoS2 layers precisely while obtaining small lateral sizes to surge the H2 -evolution rate is a tremendous challenge. Here, a bottom-up strategy is designed for the in situ growth of ultrasmall lateral-sized MoS2 with tunable layers on CdS nanorods (CN) by controlling the decomposition temperature and concentration of substrate seed (NH4 )2 MoS4 . Here, the bilayer MoS2 and CN coupling (2L-MoS2 /CN) exhibits the optimum photocatalytic activity. Compared to thicker MoS2 , the 2L-MoS2 has sufficient reduction capacity to drive photocatalytic H2 evolution and the ultrasmall lateral size provides more active sites. Meanwhile, the indirect bandgap, in contrast to the direct bandgap of the monolayer MoS2 , suppresses the carrier recombination transferred to 2L-MoS2 . Under the synergistic effect of both, 2L-MoS2 /CN has fast surface chemical reactions, resulting in the photocatalytic H2 -evolution rate of up to 41.86 mmol g-1 h-1 . A novel strategy is provided here for tuning the MoS2 layers to achieve efficient H2 evolution.

Hierarchically Periodic Macroporous Niobium Oxide Architecture for Enhanced Hydrogen Evolution.

The fabrication of periodic macroporous (PM) in Nb2O5 via morphological control is crucial for improving the photocatalytic hydrogen evolution efficiency. In this study, Nb2O5 with PM is synthesized using a straightforward colloidal crystal templating approach. This material features an open, interconnected macroporous architecture with nanoscale walls, high crystallinity, and substantial porosity. Extensive characterization reveals that this hierarchically structured Nb2O5 possesses abundant surface active sites and is capable of capturing light effectively, facilitating rapid mass transfer and diffusion of reactants and markedly suppressing the recombination of photoexcited charge carriers. Macroporous Nb2O5 exhibits superior water-splitting hydrogen evolution performance compared with its bulk and commercial counterparts, achieving a hydrogen production rate of 405 µmol g-1 h-1, surpassing that of bulk Nb2O5 (B-Nb2O5) and commercial Nb2O5 (C-Nb2O5) by factors of 5 and 33, respectively. This study proposes an innovative strategy for the design of hierarchically structured PM, thereby significantly advancing the hydrogen evolution potential of Nb2O5.

TMPRSS13 promotes the cell entry of swine acute diarrhea syndrome coronavirus.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) has caused severe intestinal diseases in pigs. It originates from bat coronaviruses HKU2 and has a potential risk of cross-species transmission, raising concerns about its zoonotic potential. Viral entry-related host factors are critical determinants of susceptibility to cells, tissues, or species, and remain to be elucidated for SADS-CoV. Type II transmembrane serine proteases (TTSPs) family is involved in many coronavirus infections and has trypsin-like catalytic activity. Here we examine all 18 members of the TTSPs family through CRISPR-based activation of endogenous protein expression in cells, and find that, in addition to TMPRSS2 and TMPRSS4, TMPRSS13 significantly facilitates SADS-CoV infection. This is confirmed by ectopic expression of TMPRSS13, and specific to trypsin-dependent SADS-CoV. Infection with pseudovirus bearing SADS-CoV spike protein indicates that TMPRSS13 acts at the entry step and is sensitive to serine protease inhibitor Camostat. Moreover, both human and pig TMPRSS13 are able to enhance the cell-cell membrane fusion and cleavage of spike protein. Overall, we demonstrate that TMPRSS13 is another host serine protease promoting the membrane-fusion entry of SADS-CoV, which may expand its host tropism by using diverse TTSPs.

Emerging trends in the coexistence of primary lung Cancer and hematologic malignancy: a comprehensive analysis of clinicopathological features and genetic abnormalities.

BACKGROUND: The incidence of multiple primary cancers (MPC), especially involving primary lung cancer (PLC) and primary hematologic malignancies (PHM), is rising. This study aims to analyze clinicopathological features, gene abnormalities, and prognostic outcomes in individuals diagnosed with PLC-PHM MPC. METHODS: A retrospective analysis included 89 patients diagnosed with PLC-PHM MPC at the Respiratory or Hematology Departments of Ruijin Hospital from 2003 to 2022 (a total of 842,047 people). Next-generation sequencing (NGS) assessed lung cancer specimens, while Polymerase Chain Reaction (PCR) and NGS were used for hematologic malignancy specimens. Statistical analysis involved survival analysis and Cox regression. RESULTS: PLC-PHM MPC incidence surged from 1.67 per year (2011-2013) to 16.3 per year (2020-2022). The primary demographic for PLC-PHM MPC consists predominantly of elderly (average age 66 years) males (59.6%), with a high prevalence of metachronous MPC (89.9%). The prevailing histological types were lung adenocarcinoma (70.8%) in lung cancer (LC) and mature B-cell lymphomas (50.6%) in hematologic malignancies (HM). Notably, in a molecular testing cohort of 38 LC patients, 84.2% of lung cancer cases exhibited driver mutations, in which EGFR mutations frequence prevalent was 74.2%. In total group of 85 cases achieved a median overall survival (mOS) of 46.2 months, with a 5-year survival rate of 37.9% and advanced LC patients with LC gene mutations achieved a mOS was 52.6 months, with a 5-year OS rate of 30.6%. The median progression-free survival (PFS) following first-line treatment of 11 advanced patients with lung cancer-associated driver gene mutations is 26.6 months. Multivariate Cox regression revealed a favorable OS associated with surgery for LC, favorable PS score, adenocarcinoma pathology of LC, and the presence of genetic abnormalities associated with HM. CONCLUSION: PLC-PHM MPC incidence is rising, characterized by a significant proportion of lung adenocarcinoma and a high prevalence of positive driver genes, especially in EGFR. Despite suffering from two primary tumors, the PLC-PHM MPC patients had superior data of both PFS and OS, suggesting an inherently intricate background of genetic abnormalities between the two kinds of tumors.

Trigonelline hydrochloride attenuates silica-induced pulmonary fibrosis by orchestrating fibroblast to myofibroblast differentiation.

BACKGROUND: Silicosis represents a paramount occupational health hazard globally, with its incidence, morbidity, and mortality on an upward trajectory, posing substantial clinical dilemmas due to limited effective treatment options available. Trigonelline (Trig), a plant alkaloid extracted mainly from coffee and fenugreek, have diverse biological properties such as protecting dermal fibroblasts against ultraviolet radiation and has the potential to inhibit collagen synthesis. However, it's unclear whether Trig inhibits fibroblast activation to attenuate silicosis-induced pulmonary fibrosis is unclear. METHODS: To evaluate the therapeutic efficacy of Trig in the context of silicosis-related pulmonary fibrosis, a mouse model of silicosis was utilized. The investigation seeks to elucidated Trig's impact on the progression of silica-induced pulmonary fibrosis by evaluating protein expression, mRNA levels and employing Hematoxylin and Eosin (H&E), Masson's trichrome, and Sirius Red staining. Subsequently, we explored the mechanism underlying of its functions. RESULTS: In vivo experiment, Trig has been demonstrated the significant efficacy in mitigating SiO2-induced silicosis and BLM-induced pulmonary fibrosis, as evidenced by improved histochemical staining and reduced fibrotic marker expressions. Additionally, we showed that the differentiation of fibroblast to myofibroblast was imped in Trig + SiO2 group. In terms of mechanism, we obtained in vitro evidence that Trig inhibited fibroblast-to-myofibroblast differentiation by repressing TGF-ß/Smad signaling according to the in vitro evidence. Notably, our finding indicated that Trig seemed to be safe in mice and fibroblasts. CONCLUSION: In summary, Trig attenuated the severity of silicosis-related pulmonary fibrosis by alleviating the differentiation of myofibroblasts, indicating the development of novel therapeutic approaches for silicosis fibrosis.

Full quantitative resource utilization of raw mustard waste through integrating a comprehensive approach for producing hydrogen and soil amendments.

BACKGROUND: Pickled mustard, the largest cultivated vegetable in China, generates substantial waste annually, leading to significant environmental pollution due to challenges in timely disposal, leading to decomposition and sewage issues. Consequently, the imperative to address this concern centers on the reduction and comprehensive resource utilization of raw mustard waste (RMW). To achieve complete and quantitative resource utilization of RMW, this study employs novel technology integration for optimizing its higher-value applications. RESULTS: Initially, subcritical hydrothermal technology was applied for rapid decomposition, with subsequent ammonia nitrogen removal via zeolite. Thereafter, photosynthetic bacteria, Rhodopseudomonas palustris, were employed to maximize hydrogen and methane gas production using various fermentation enhancement agents. Subsequent solid-liquid separation yielded liquid fertilizer from the fermented liquid and soil amendment from solid fermentation remnants. Results indicate that the highest glucose yield (29.6 ± 0.14) was achieved at 165-173℃, with a total sugar content of 50.2 g/L and 64% glucose proportion. Optimal ammonia nitrogen removal occurred with 8 g/L zeolite and strain stable growth at 32℃, with the highest OD600 reaching 2.7. Several fermentation promoters, including FeSO4, Neutral red, Na2S, flavin mononucleotide, Nickel titanate, Nickel oxide, and Mixture C, were evaluated for hydrogen production. Notably, Mixture C resulted in the maximum hydrogen production (756 mL), a production rate of 14 mL/h, and a 5-day stable hydrogen production period. Composting experiments enhanced humic acid content and organic matter (OM) by 17% and 15%, respectively. CONCLUSIONS: This innovative technology not only expedites RMW treatment and hydrogen yield but also substantially enriches soil fertility. Consequently, it offers a novel approach for low-carbon, zero-pollution RMW management. The study's double outcomes extend to large-scale RMW treatment based on the aim of full quantitative resource utilization of RMW. Our method provides a valuable reference for waste management in similar perishable vegetable plantations.

Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin.

Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health 1 . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) 2-10 . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.

Effects of Kv1.3 knockout on pyramidal neuron excitability and synaptic plasticity in piriform cortex of mice.

Kv1.3 belongs to the voltage-gated potassium (Kv) channel family, which is widely expressed in the central nervous system and associated with a variety of neuropsychiatric disorders. Kv1.3 is highly expressed in the olfactory bulb and piriform cortex and involved in the process of odor perception and nutrient metabolism in animals. Previous studies have explored the function of Kv1.3 in olfactory bulb, while the role of Kv1.3 in piriform cortex was less known. In this study, we investigated the neuronal changes of piriform cortex and feeding behavior after smell stimulation, thus revealing a link between the olfactory sensation and body weight in Kv1.3 KO mice. Coronal slices including the anterior piriform cortex were prepared, whole-cell recording and Ca2+ imaging of pyramidal neurons were conducted. We showed that the firing frequency evoked by depolarization pulses and Ca2+ influx evoked by high K+ solution were significantly increased in pyramidal neurons of Kv1.3 knockout (KO) mice compared to WT mice. Western blotting and immunofluorescence analyses revealed that the downstream signaling molecules CaMKII and PKCα were activated in piriform cortex of Kv1.3 KO mice. Pyramidal neurons in Kv1.3 KO mice exhibited significantly reduced paired-pulse ratio and increased presynaptic Cav2.1 expression, proving that the presynaptic vesicle release might be elevated by Ca2+ influx. Using Golgi staining, we found significantly increased dendritic spine density of pyramidal neurons in Kv1.3 KO mice, supporting the stronger postsynaptic responses in these neurons. In olfactory recognition and feeding behavior tests, we showed that Kv1.3 conditional knockout or cannula injection of 5-(4-phenoxybutoxy) psoralen, a Kv1.3 channel blocker, in piriform cortex both elevated the olfactory recognition index and altered the feeding behavior in mice. In summary, Kv1.3 is a key molecule in regulating neuronal activity of the piriform cortex, which may lay a foundation for the treatment of diseases related to piriform cortex and olfactory detection.

Rituximab may affect T lymphocyte subsets balance in primary membranous nephropathy.

BACKGROUND: The aim of this study was to investigate the effects and significance of rituximab (RTX) on the levels of T lymphocyte subsets in patients diagnosed with primary membranous nephropathy (PMN). METHODS: A total of 58 PMN patients and 25 healthy donors were chosen as the subjects. Among the PMN patients, 40 individuals received RTX treatment and completed at least 6 months of follow-up. All subjects underwent flow cytometry analysis to determine the peripheral blood lymphocyte subsets. The changes in anti-PLA2R antibody titers and 24-hour urinary protein levels were evaluated by ELISA and Biuret method before and after treatment. RESULTS: (1) The PMN group exhibited a significantly greater percentage of peripheral blood CD3-CD19+ B cells than the healthy group, which is consistent with the findings of previous reports. Additionally, compared with those in the peripheral blood of healthy individuals, the numbers of CD4+ central memory T cells, CD4+ effector memory T cells, CD4+/CD8+, and CD4+CD25+ T cells in the PMN peripheral blood were markedly greater. However, the number of peripheral blood Treg cells was reduced in the PMN group. (2) After 6 months of RTX treatment, PMN patients exhibited significant decreases in anti-PLA2R antibody titers, 24-hour urinary protein levels, and peripheral blood CD3-CD19+ B cells. Importantly, RTX administration decreased CD4+CD25+ T cells and CD4+/CD8+ in the peripheral blood of PMN patients and improved Treg cell levels. (3) RTX treatment induced alterations in the CD4+ T lymphocyte subsets in PMN patients, which did not correlate with B lymphocyte counts or anti-PLA2R antibody titers. CONCLUSIONS: RTX treatment might have a beneficial impact on cellular immunity by effectively restoring the balance of CD4+ T lymphocyte subsets in PMN patients, which is beyond its effects on B cells and antibody production. TRIAL REGISTRATION: The research was registered at the First Affiliated Hospital of Soochow University. REGISTRATION NUMBER: MR-32-23-016211. Registration Date: May 31, 2023.

Incidence of noninvasive ventilation failure and mortality in patients with acute respiratory distress syndrome: a systematic review and proportion meta-analysis.

BACKGROUND: Noninvasive ventilation (NIV) is commonly used in patients with acute respiratory distress syndrome (ARDS). However, the incidence and distribution of treatment failure are unclear. METHODS: A comprehensive online search was conducted to select potentially eligible studies with reports of the rate of NIV failure in patients with ARDS. A manual search was also performed to identify additional studies. Data were extracted to calculate the pooled incidences of NIV failure and mortality. Based on oxygenation, the severity of the disease was classified as mild, moderate, or severe ARDS. Based on etiologies, ARDS was defined as being of pulmonary origin or extrapulmonary origin. RESULTS: We enrolled 90 studies in this meta-analysis, involving 98 study arms. The pooled incidence of NIV failure was 48% (n = 5847, 95% confidence interval [CI]: 43-52%). The pooled incidence of ICU mortality was 29% (n = 2363, 95%CI: 22-36%), and that of hospital mortality was 33% (n = 2927, 95%CI: 27-40%). In patients with mild, moderate, and severe ARDS, the pooled incidence of NIV failure was 30% (n = 819, 95%CI: 21-39%), 51% (n = 1332, 95%CI: 43-60%), and 71% (n = 525, 95%CI: 62-79%), respectively. In patients with pulmonary ARDS, it was 45% (n = 2687, 95%CI: 39-51%). However, it was 30% (n = 802, 95%CI: 21-38%) in those with extrapulmonary ARDS. In patients with immunosuppression, the incidence of NIV failure was 62% (n = 806, 95%CI: 50-74%). However, it was 46% (n = 5041, 95%CI: 41-50%) in those without immunosuppression. CONCLUSIONS: Nearly half of patients with ARDS experience NIV failure. The incidence of NIV failure increases with increasing ARDS severity. Pulmonary ARDS seems to have a higher rate of NIV failure than extrapulmonary ARDS. ARDS patients with immunosuppression have the highest rate of NIV failure.

A rare case report of infratentorial cisternal angiolipoma with review of literature.

Angiolipomas are slow-growing benign mesenchymal-derived tumors consisting of mature adipocytes and thin-walled blood vessels. While the majority of angiolipomas are found in subcutaneous tissues, rarely there are case reports of intracranial lesions. We present a case of cisternal angiolipoma in a 10-year-old female. She presented with vague symptoms like dizziness without neurological deficits and radiological evaluation confirmed a left-sided infratentorial cisternal partially enhancing mass. She underwent craniotomy and had complete resection of the mass, which was histologically composed of mature adipocytes and blood vessels, consistent with angiolipoma. A review of the literature found only 18 cases of intracranial angiolipoma ever reported with our case representing the first case of infratentorial cisternal region.