Catalytic Regio- and Enantioselective Remote Hydrocarboxylation of Unactivated Alkenes with CO2.

The catalytic regio- and enantioselective hydrocarboxylation of alkenes with carbon dioxide is a straightforward strategy to construct enantioenriched α-chiral carboxylic acids but remains a big challenge. Herein we report the first example of catalytic highly enantio- and site-selective remote hydrocarboxylation of a wide range of readily available unactivated alkenes with abundant and renewable CO2 under mild conditions enabled by the SaBOX/Ni catalyst. The key to this success is utilizing the chiral SaBOX ligand, which combines with nickel to simultaneously control both chain-walking and the enantioselectivity of carboxylation. This process directly furnishes a range of different alkyl-chain-substituted or benzo-fused α-chiral carboxylic acids bearing various functional groups in high yields and regio- and enantioselectivities. Furthermore, the synthetic utility of this methodology was demonstrated by the concise synthesis of the antiplatelet aggregation drug (R)-indobufen from commercial starting materials.

Iron Overload-induced Ferroptosis as a Target for Protection against Obliterative Bronchiolitis after Orthotopic Tracheal Transplantation in Mice.

INTRODUCTION: The major complication of Obliterative Bronchiolitis (OB) is characterized by epithelial cell loss, fibrosis, and luminal occlusion of the terminal small airways, which limits the long-term survival of the recipient after lung transplantation. However, the underlying mechanisms are still not fully clarified. This research aims to investigate whether iron overload-induced ferroptosis is involved in OB development and provide a new target for OB prevention. MATERIALS AND METHODS: Allograft orthotopic tracheal transplantation in mice was applied in our study. Ferrostatin-1 and deferoxamine were administrated to inhibit ferroptosis and get rid of ferric iron, while iron dextran was used to induce an iron overload condition in the recipient. The histological examination, luminal occlusion rate, collagen deposition, iron level, ferroptosis marker (GPX4, PTGS2), and mitochondrial morphological changes of the graft were evaluated in mice. RESULTS: Our research indicated that ferroptosis and iron overload contribute to OB development, while ferroptosis inhibition and iron chelator could reverse the changes. Iron overload exacerbated OB development after orthotopic tracheal transplantation via promoting ferroptosis. CONCLUSION: Overall, this research demonstrated that iron overload-induced ferroptosis is involved in OB, which may be a potential therapeutic target for OB after lung transplantation.

Real-time PCR-based quantitative microbiome profiling elucidates the microbial dynamic succession in backslopping fermentation of Taiwanese pickled cabbage.

BACKGROUND: Microbiota succession determines the flavor and quality of fermented foods. Quantitative PCR-based quantitative microbiome profiling (QMP) has been applied broadly for microbial analysis from absolute abundance perspectives, transforming microbiota ratios into counts by normalizing 16S ribosomal RNA (16S rRNA) gene sequencing data with gene copies quantified by quantitative PCR. However, the application of QMP in fermented foods is still limited. RESULTS: QMP elucidated microbial succession of Taiwanese pickled cabbage. In the spontaneous first-round fermentation (FR), the 16S rRNA gene copies of total bacteria increased from 6.1 to 10 log copies mL-1. The dominant lactic acid bacteria genera were successively Lactococcus, Leuconostoc and Lactiplantibacillus. Despite the decrease in the proportion of Lactococcus during the succession, the absolute abundance of Lactococcus still increased. In the backslopping second-round fermentation (SR), the total bacteria 16S rRNA gene copies increased from 7.6 to 9.9 log copies mL-1. The addition of backslopping starter and vinegar rapidly led to a homogenous microbial community dominated by Lactiplantibacillus. The proportion of Lactiplantibacillus remained consistently around 90% during SR, whereas its absolute abundance exhibited a continuous increase. In SR without vinegar, Leuconostoc consistently dominated the fermentation. CONCLUSION: The present study highlights that compositional analysis would misinterpret microbial dynamics, whereas QMP reflected the real succession profiles and unveiled the essential role of vinegar in promoting Lactiplantibacillus dominance in backslopping fermentation of Taiwanese pickled cabbage. Quantitative microbiome profiling (QMP) was found to be a more promising approach for the detailed observation of microbiome succession in food fermentation compared to compositional analysis. © 2024 Society of Chemical Industry.

Tunable nonreciprocal metasurfaces based on a nonlinear quasi-bound state in the continuum.

Nonreciprocal devices are essential and crucial in optics for source protection and signal separation. A hybrid grating system consisting of a silicon grating, a graphene layer, and a silicon waveguide layer is employed to create a high-Q quasi-BIC (bound state in the continuum). Then, the high-Q properties of the quasi-BIC are harnessed to enhance the third-order nonlinear effect of silicon, thereby improving the nonreciprocal characteristics of the device. The nonreciprocal transmittance ratio of the device can be tunable by adjusting the graphene Fermi energy level, achieving tunability ranging from 0.0865 to 30.57 dB. It also enables the best performance of the device over a wider range of frequency bands. This study provides a new, to the best of our knowledge, method for designing tunable nonreciprocal devices with a wide range of potential applications.

Predictive Factors for Iliac Limb Occlusions After Endovascular Abdominal Aneurysm Repair: Determined from Aortoiliac Anatomy, Endovascular Procedures, and Aneurysmal Remodeling.

Purpose: Iliac limb occlusion (ILO) is a serious complication of endovascular abdominal aneurysm repair (EVAR). This study aimed to identify predictive factors for ILO derived from aortoiliac morphology, endovascular procedure-related parameters, and aneurysmal remodeling characteristics. Patients and Methods: Patient demographics, pre-EVAR anatomical characteristics of the aneurysm, endovascular procedure details, and post-EVAR aneurysmal remodeling outcomes were analyzed and compared using univariate analysis. Statistically significant factors were subsequently subjected to Cox regression and Kaplan-Meier analyses. Results: Between January 2013 and April 2022, 66 patients were included in this study. Fourteen patients presented with ILO and were compared with 52 control patients with patent endograft limb over at least 1-year of follow-up. The tortuosity indices of the common iliac artery (CIA) and endograft iliac limb to vessel oversizing were significantly larger in the ILO group than in the patent endograft limb group. The CIA index of tortuosity ≥1.08, and endograft iliac limb to vessel oversizing ≥18.8% were independent predictors for ILO. During the follow-up of all patients, the proximal aortic neck and CIA diameters increased, aneurysm sac diameter decreased, and aortic neck and aortic length increased. The aortoiliac length increased over time in patients with patent endograft limb but not in patients with ILO. A change in the lowest renal artery-left iliac bifurcation distance ≦0.07 mm increased the risk of ILO. Conclusion: ILO is predisposed to occur when the CIA index of tortuosity ≥1.08 and endograft iliac limb to vessel oversizing ≥18.8% are present. Significant aortoiliac remodeling, including proximal aortic neck dilatation, neck straightening, aneurysmal sac regression, iliac artery enlargement, and aortic lengthening, occurs after EVAR. Aortoiliac elongation was observed in patients with patent endograft limb, but not in patients with ILO. ILO was associated with a change in the lowest renal artery-left iliac bifurcation from the postoperative measurements ≦ 0.07 mm.

Strain-induced ferroelectric polarization reversal without undergoing geometric inversion in blue SiSe monolayer.

Ferroelectricity in two-dimensional (2D) systems generally arises from phonons and has been widely investigated. On the contrary, electronic ferroelectricity in 2D systems has been rarely studied. Using first-principles calculations, the ferroelectric behavior of the buckled blue SiSe monolayer under strain are explored. It is found that the direction of the out-of-plane ferroelectric polarization can be reversed by applying an in-plane strain. And such polarization switching is realized without undergoing geometric inversion. Besides, the strain-triggered polarization reversal emerges in both biaxial and uniaxial strain cases, indicating it is an intrinsic feature of such a system. Further analysis shows that the polarization switching is the result of the reversal of the magnitudes of the positive and negative charge center vectors. And the variation of buckling is found to play an important role, which results in the switch. Moreover, a non-monotonic variation of band gap with strain is revealed. Our findings throws light on the investigation of novel electronic ferroelectric systems.

Single-cell analysis of anti-BCMA CAR T cell therapy in patients with central nervous system autoimmunity.

Chimeric antigen receptor (CAR) T cell immunotherapy for the treatment of neurological autoimmune diseases is promising, but CAR T cell kinetics and immune alterations after treatment are poorly understood. Here, we performed single-cell multi-omics sequencing of paired cerebrospinal fluid (CSF) and blood samples from patients with neuromyelitis optica spectrum disorder (NMOSD) treated with anti-B cell maturation antigen (BCMA) CAR T cells. Proliferating cytotoxic-like CD8+ CAR T cell clones were identified as the main effectors in autoimmunity. Anti-BCMA CAR T cells with enhanced features of chemotaxis efficiently crossed the blood-CSF barrier, eliminated plasmablasts and plasma cells in the CSF, and suppressed neuroinflammation. The CD44-expressing early memory phenotype in infusion products was potentially associated with CAR T cell persistence in autoimmunity. Moreover, CAR T cells from patients with NMOSD displayed distinctive features of suppressed cytotoxicity compared with those from hematological malignancies. Thus, we provide mechanistic insights into CAR T cell function in patients with neurological autoimmune disease.

Ldl-stimulated microglial activation exacerbates ischemic white matter damage.

The role of microglia in triggering the blood-brain barrier (BBB) impairment and white matter damage after chronic cerebral hypoperfusion is unclear. Here we demonstrated that the vessel-adjacent microglia were specifically activated by the leakage of plasma low-density lipoprotein (LDL), which led to BBB breakdown and ischemic demyelination. Interestingly, we found that LDL stimulation enhanced microglial phagocytosis, causing excessive engulfment of myelin debris and resulting in an overwhelming lipid burden in microglia. Surprisingly, these lipid-laden microglia exhibited a suppressed profile of inflammatory response and compromised pro-regenerative properties. Microglia-specific knockdown of LDLR or systematic medication lowering circulating LDL-C showed protective effects against ischemic demyelination. Overall, our findings demonstrated that LDL-stimulated vessel-adjacent microglia possess a disease-specific molecular signature, characterized by suppressed regenerative properties, which is associated with the propagation of demyelination during ischemic white matter damage.

Mapping SCA1 regional vulnerabilities reveals neural and skeletal muscle contributions to disease.

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by an expanded polyglutamine tract in the widely expressed ataxin-1 (ATXN1) protein. To elucidate anatomical regions and cell types that underlie mutant ATXN1-induced disease phenotypes, we developed a floxed conditional knockin mouse (f-ATXN1146Q/2Q) with mouse Atxn1 coding exons replaced by human ATXN1 exons encoding 146 glutamines. f-ATXN1146Q/2Q mice manifested SCA1-like phenotypes including motor and cognitive deficits, wasting, and decreased survival. Central nervous system (CNS) contributions to disease were revealed using f-ATXN1146Q/2Q;Nestin-Cre mice, which showed improved rotarod, open field, and Barnes maze performance by 6-12 weeks of age. In contrast, striatal contributions to motor deficits using f-ATXN1146Q/2Q;Rgs9-Cre mice revealed that mice lacking ATXN1146Q/2Q in striatal medium-spiny neurons showed a trending improvement in rotarod performance at 30 weeks of age. Surprisingly, a prominent role for muscle contributions to disease was revealed in f-ATXN1146Q/2Q;ACTA1-Cre mice based on their recovery from kyphosis and absence of muscle pathology. Collectively, data from the targeted conditional deletion of the expanded allele demonstrated CNS and peripheral contributions to disease and highlighted the need to consider muscle in addition to the brain for optimal SCA1 therapeutics.

Suppressing inflammatory signals and apoptosis-linked sphingolipid metabolism underlies therapeutic potential of Qing-Jin-Hua-Tan decoction against chronic obstructive pulmonary disease.

Background: Qing-Jin-Hua-Tan decoction (QJHTD) is a classic traditional Chinese medicine (TCM) prescription that first appeared in the ancient book Yi-Xue-Tong-Zhi. QJHTD has shown effectiveness for treating chronic obstructive pulmonary disease (COPD), although its mechanisms of action are still perplexing. The molecular mechanisms underlying the curative effects of QJHTD on COPD is worth exploring. Methods: In vitro antiapoptotic and antiinflammatory activities of QJHTD were evaluated using cell viability, proliferation, apoptosis rate, and expression of IL-1ß and TNF-α in BEAS-2B and RAW264.7 cells challenged with cigarette smoke (CS) extract (CSE) and lipopolysaccharide (LPS). In vivo therapeutic activities of QJHTD were evaluated using respiratory parameters (peak inspiratory flow (PIFb) and peak expiratory flow (PEFb) values), histopathology (mean linear intercept, MLI), and proinflammatory cytokine (IL-1ß and TNF-α) and cleaved caspase-3 (c-Casp3) levels in the lung tissue of CS-LPS-exposed BALB/c mice. Network pharmacology-based prediction, transcriptomic analysis, and metabolic profiling were employed to investigate the signaling molecules and metabolites pertinent to the anti-COPD action of QJHTD. Results: Increased cell viability and proliferation with decreased apoptosis rate and proinflammatory cytokine expression were noted after QJHTD intervention. QJHTD administration elevated PEFb and PIFb values, reduced MLI, and inhibited IL-1ß, TNF-α, and c-Casp3 expression in vivo. Integrated network pharmacology-transcriptomics revealed that suppressing inflammatory signals (IL-1ß, IL-6, TNF, IκB-NF-κB, TLR, and MAPK) and apoptosis contributed to the anti-COPD property of QJHTD. Metabolomic profiling unveiled prominent roles for the suppression of apoptosis and sphingolipid (SL) metabolism and the promotion of choline (Ch) metabolism in the anti-COPD effect of QJHTD. Integrative transcriptomics-metabolomics unraveled the correlation between SL metabolism and apoptosis. In silico molecular docking revealed that acacetin, as an active compound in QJHTD, could bind with high affinity to MEK1, MEK2, ERK1, ERK2, Bcl2, NF-κB, and alCDase target proteins. Conclusion: The therapeutic effect of QJHTD on COPD is dependent on regulating inflammatory signals and apoptosis-directed SL metabolism. These findings provide deeper insights into the molecular mechanism of action of QJHTD against COPD and justify its theoretical promise in novel pharmacotherapy for this multifactorial disease.

B cell lineage reconstitution underlies CAR-T cell therapeutic efficacy in patients with refractory myasthenia gravis.

B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly relapsed and refractory myasthenia gravis (one with AChR-IgG, and one with MuSk-IgG). Both patients exhibited favorable safety profiles and persistent clinical improvements over 18 months. Reconstitution of B-cell lineages with sustained reduced pathogenic autoantibodies might underlie the therapeutic efficacy. To identify the possible mechanisms underlying the therapeutic efficacy of CAR-T cells in these patients, longitudinal single-cell RNA and TCR sequencing was conducted on serial blood samples post infusion as well as their matching infusion products. By tracking the temporal evolution of CAR-T phenotypes, we demonstrated that proliferating cytotoxic-like CD8 clones were the main effectors in autoimmunity, whereas compromised cytotoxic and proliferation signature and profound mitochondrial dysfunction in CD8+ Te cells before infusion and subsequently defect CAR-T cells after manufacture might explain their characteristics in these patients. Our findings may guide future studies to improve CAR T-cell immunotherapy in autoimmune diseases.

Catalytic Regio- and Enantioselective Boracarboxylation of Arylalkenes with CO2 and Diboron.

Catalytic asymmetric carboxylation of readily available alkenes with CO2, an abundant and sustainable one-carbon building block, that gives access to value-added α-stereogenic carboxylic acids in an atom- and step-economic manner is highly attractive. However, it has remained a formidable challenge for the synthetic community. Here, the first example of Cu-catalyzed highly regio- and enantioselective boracarboxylation reaction on various arylalkenes with diboron under an atmospheric pressure of CO2 is described, which afforded a variety of chiral ß-boron-functionalized α-aryl carboxylic acids with up to 87% yield and 97% ee under mild conditions. Importantly, α-substituted arylalkenes could also be subject to this protocol with excellent enantiopurities, thereby rendering an efficient approach for the generation of enantioenriched carboxylic acids with an α-chiral all-carbon quaternary center. Moreover, high functional group tolerance, scalable synthesis, and facile access to bioactive compounds, like (-)-scopolamine, (-)-anisodamine, and (-)-tropicamide, further demonstrated the synthetic utility of this strategy.

Single-cell analysis of refractory anti-SRP necrotizing myopathy treated with anti-BCMA CAR-T cell therapy.

Immune-mediated necrotizing myopathy (IMNM) is an autoimmune disorder associated with the presence of autoantibodies, characterized by severe clinical presentation with rapidly progressive muscular weakness and elevated levels of creatine kinase, while traditional pharmacological approaches possess varying and often limited effects. Considering the pathogenic role of autoantibodies, chimeric antigen receptor (CAR)-T cells targeting B cell maturation antigen (BCMA) have emerged as a promising therapeutic strategy. We reported here a patient with anti-signal recognition particle IMNM refractory to multiple available therapies, who was treated with BCMA-targeting CAR-T cells, exhibited favorable safety profiles, sustained reduction in pathogenic autoantibodies, and persistent clinical improvements over 18 mo. Longitudinal single-cell RNA, B cell receptor, T cell receptor sequencing analysis presented the normalization of immune microenvironment after CAR-T cell infusion, including reconstitution of B cell lineages, replacement of T cell subclusters, and suppression of overactivated immune cells. Analysis on characteristics of CAR-T cells in IMNM demonstrated a more active expansion of CD8+ CAR-T cells, with a dynamic phenotype shifting pattern similar in CD4+ and CD8+ CAR-T cells. A comparison of CD8+ CAR-T cells in patients with IMNM and those with malignancies collected at different timepoints revealed a more NK-like phenotype with enhanced tendency of cell death and neuroinflammation and inhibited proliferating ability of CD8+ CAR-T cells in IMNM while neuroinflammation might be the distinct characteristics. Further studies are warranted to define the molecular features of CAR-T cells in autoimmunity and to seek higher efficiency and longer persistence of CAR-T cells in treating autoimmune disorders.

Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory demyelinating disease of the central nervous system (CNS) accompanied by blood-brain barrier (BBB) disruption. Dysfunction in microglial lipid metabolism is believed to be closely associated with the neuropathology of NMOSD. However, there is limited evidence on the functional relevance of circulating lipids in CNS demyelination, cellular metabolism, and microglial function. Here, we found that serum low-density lipoprotein (LDL) was positively correlated with markers of neurological damage in NMOSD patients. In addition, we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB, directly activating microglia. This activation leads to excessive phagocytosis of myelin debris, inhibition of lipid metabolism, and increased glycolysis, ultimately exacerbating myelin damage. We also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in NMOSD. These findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage, highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.

Multifunctional ytterbium oxide buffer for perovskite solar cells.

Perovskite solar cells (PSCs) comprise a solid perovskite absorber sandwiched between several layers of different charge-selective materials, ensuring unidirectional current flow and high voltage output of the devices1,2. A 'buffer material' between the electron-selective layer and the metal electrode in p-type/intrinsic/n-type (p-i-n) PSCs (also known as inverted PSCs) enables electrons to flow from the electron-selective layer to the electrode3-5. Furthermore, it acts as a barrier inhibiting the inter-diffusion of harmful species into or degradation products out of the perovskite absorber6-8. Thus far, evaporable organic molecules9,10 and atomic-layer-deposited metal oxides11,12 have been successful, but each has specific imperfections. Here we report a chemically stable and multifunctional buffer material, ytterbium oxide (YbOx), for p-i-n PSCs by scalable thermal evaporation deposition. We used this YbOx buffer in the p-i-n PSCs with a narrow-bandgap perovskite absorber, yielding a certified power conversion efficiency of more than 25%. We also demonstrate the broad applicability of YbOx in enabling highly efficient PSCs from various types of perovskite absorber layer, delivering state-of-the-art efficiencies of 20.1% for the wide-bandgap perovskite absorber and 22.1% for the mid-bandgap perovskite absorber, respectively. Moreover, when subjected to ISOS-L-3 accelerated ageing, encapsulated devices with YbOx exhibit markedly enhanced device stability.

Soluble TREM2 triggers microglial dysfunction in neuromyelitis optica spectrum disorders.

Microglia-mediated neuroinflammation contributes to acute demyelination in neuromyelitis optica spectrum disorders (NMOSD). Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in the CSF has been associated with microglial activation in several neurodegenerative diseases. However, the basis for this immune-mediated attack and the pathophysiological role of sTREM2 in NMOSD remain to be elucidated. Here, we performed Mendelian randomization analysis and identified a genetic association between increased CSF sTREM2 and NMOSD risk. CSF sTREM2 was elevated in patients with NMOSD and was positively correlated with neural injury and other neuroinflammation markers. Single-cell RNA sequencing of human macrophage/microglia-like cells in CSF, a proxy for microglia, showed that increased CSF sTREM2 was positively associated with microglial dysfunction in patients with NMOSD. Furthermore, we demonstrated that sTREM2 is a reliable biomarker of microglial activation in a mouse model of NMOSD. Using unbiased transcriptomic and lipidomic screens, we identified that excessive activation, overwhelmed phagocytosis of myelin debris, suppressed lipid metabolism and enhanced glycolysis underlie sTREM2-mediated microglial dysfunction, possibly through the nuclear factor kappa B (NF-κB) signalling pathway. These molecular and cellular findings provide a mechanistic explanation for the genetic association between CSF sTREM2 and NMOSD risk and indicate that sTREM2 could be a potential biomarker of NMOSD progression and a therapeutic target for microglia-mediated neuroinflammation.

Terahertz large-area unidirectional surface magnetoplasmon and its applications.

Unidirectional surface waves in nonreciprocal plasmonic platforms with nonlocal effects have been a topic of significant interest and some controversy. In this study, we present a scheme to achieve unidirectional surface magnetoplasmons (USMPs) with large modal areas at terahertz frequencies. Such large-area USMPs (LUSMPs) exist in a metal-UENZ (uniaxial-[Formula: see text]-near-zero)-Si-InSb structure under external magnetic field, where the effect of nonlocality is included. The field of the LUSMP extends almost uniformly in the UENZ layer with a thickness of wavelength scale, thus its modal size can be represented by the UENZ-layer thickness. Due to the modal energy primarily distributed in the thick UENZ layer, the nonlocality-induced leakage of the LUSMP is significantly reduced by an order of magnitude, compared to previous USMP existing at interface between InSb and opaque isotropic medium. Due to their large modal sizes, such LUSMPs can be efficiently excited by terahertz radiations directly from free space. In addition, LUSMPs offer high degree of freedom for manipulating terahertz waves, such as energy squeezing and trapping. Based on LUSMPs, a terahertz free-space isolator is also developed. Our findings have important implications to the development of innovative plasmonic devices in terahertz regime.

A retrospective observational study on maternal and neonatal outcomes of COVID-19: Does the mild SARS-CoV-2 infection affect the outcome?

Background: Currently, several SARS-CoV-2 variants, including Omicron, are still circulating globally. This underscores the necessity for a comprehensive understanding of their impact on obstetric and neonatal outcomes in pregnant women, even in cases of mild infection. Methods: We conducted a retrospective, single-center observational study to investigate the association between gestational SARS-CoV-2 infection and maternal-fetal outcomes in the Chinese population. The study enrolled 311 pregnant patients with SARS-CoV-2 infection (exposure group) and 205 uninfected pregnant patients (control group). We scrutinized the hospital records to collect data on demographics, clinical characteristics, and maternal and neonatal outcomes for subsequently comparison. Results: Similar characteristics were observed in both groups, including maternal age, height, BMI, gravidity, parity, and comorbidities (p > 0.05). A majority (97.4%) of pregnant women in the exposure group with COVID-19 experienced mild clinical symptoms, with fever (86.5%) and cough (74.3%) as the primary symptoms. The exposure group exhibited significantly higher incidences of cesarean section and fetal distress compared to the control group (p < 0.05). Furthermore, pregnant women in the exposure group showed reduced levels of hemoglobin and high-sensitivity C-reactive protein, while experiencing significantly increased levels of lymphocytes, prothrombin time, alanine aminotransferase, and aspartate aminotransferase (p < 0.05). Notably, recent SARS-CoV-2 infection prior to delivery appeared to have an adverse impact on liver function, blood and coagulation levels in pregnant women. When comparing the two groups, there were no significant differences in the postpartum hemorrhage rate, premature birth rate, birth weight, neonatal asphyxia rate, neonatal department transfer rate, and neonatal pneumonia incidence. Conclusions: Our study suggests that mild COVID-19 infection during pregnancy does not have detrimental effects on maternal and neonatal outcomes. However, the increased risks of events such as fetal distress and cesarean section, coupled with potential alterations in physical function, reveal the consequences of SARS-CoV-2 infection during pregnancy, even in mild cases. These findings emphasize the importance of proactive management and monitoring of pregnant individuals with COVID-19.

Dioscin Mediated IgA Nephropathy Alleviation by Inhibiting B Cell Activation In Vivo and Decreasing Galactose-Deficient IgA1 Production In Vitro.

The increase of circulating galactose-deficient IgA1 (Gd-IgA1) is caused by excessive activation of IgA-positive secretory cells in the process of mucosal immune responses, which is a critical link in the pathogenesis of IgA nephropathy (IgAN). Peyer's patch, the prominent place where B lymphocytes are transformed into IgA-secreting plasma cells, is the primary source of IgA. In addition, the lower expression of core 1ß-1,3-galactosyltransferase (C1GalT1) and its molecular chaperone, C1GalT1-specific molecular chaperone (Cosmc), is related to abnormal glycosylation of IgA1 in IgAN patients. Our clinical experience shows that Dioscoreae Nipponicae Rhizoma's (DNR) herbal medicine can relieve proteinuria and hematuria and improve renal function in IgAN patients. Dioscin (DIO) is one of the main active ingredients of DNR, which has various pharmacological activities. This study explores DIO's possible mechanism in treating IgAN.The IgAN model mouse was established by mucosal immune induction. The mice were divided into the control, model, and DIO gavage groups. The glomerular IgA deposition in mice, renal pathological changes, and B cell markers CD20 and CXCR5 expression in Peyer's patch were detected by immunofluorescence and immunohistochemistry. After lipopolysaccharide (LPS) stimulation, DIO's effects on DAKIKI cells proliferation, IgA and Gd-IgA1 secretion, C1GalT1, and Cosmc expression were studied by cell counting kit-8 (CCK-8) assay, enzyme-linked immunosorbent assay (ELISA) test, quantitative real-time polymerase chain reaction (QRT-PCR), and western blotting (WB). In in vivo studies, IgA deposition accompanied by glomerular mesangial hyperplasia and increased expression of CD20 and CXCR5 in Peyer's patch in the IgAN model mouse was alleviated by DIO. In vitro studies showed 0.25 µg/mL to 1.0 µg/mL DIO inhibited LPS-induced DAKIKI cell proliferation, IgA and Gd-IgA1 secretion, and up-regulated the mRNA and protein expression of C1GalT1 and Cosmc. This study demonstrates that DIO may reduce Gd-IgA1 production by inhibiting excessive activation of IgA-secreting cells and up-regulating C1GALT1/Cosmc expression.

Trem2 deficiency attenuates microglial phagocytosis and autophagic-lysosomal activation in white matter hypoperfusion.

Chronic cerebral hypoperfusion leads to sustained demyelination and a unique response of microglia. Triggering receptor expressed on myeloid cells 2 (Trem2), which is expressed exclusively on microglia in the central nervous system (CNS), plays an essential role in microglial response in various CNS disorders. However, the specific role of Trem2 in chronic cerebral hypoperfusion has not been elucidated. In this study, we investigated the specific role of Trem2 in a mouse model of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis (BCAS). Our results showed that chronic hypoperfusion induced white matter demyelination, microglial phagocytosis, and activation of the microglial autophagic-lysosomal pathway, accompanied by an increase in Trem2 expression. After Trem2 knockout, we observed attenuation of white matter lesions and microglial response. Trem2 deficiency also suppressed microglial phagocytosis and relieved activation of the autophagic-lysosomal pathway, leading to microglial polarization towards anti-inflammatory and homeostatic phenotypes. Furthermore, Trem2 knockout inhibited lipid droplet accumulation in microglia in vitro. Collectively, these findings suggest that Trem2 deficiency ameliorated microglial phagocytosis and autophagic-lysosomal activation in hypoperfusion-induced white matter injury, and could be a promising target for the treatment of chronic cerebral hypoperfusion.