PPP4C facilitates homologous recombination DNA repair by dephosphorylating PLK1 during early embryo development.

Mammalian early embryo cells have complex DNA repair mechanisms to maintain genomic integrity, and homologous recombination (HR) plays the main role in response to double-strand DNA breaks (DSBs) in these cells. Polo-like kinase 1 (PLK1) participates in the HR process and its overexpression has been shown to occur in a variety of human cancers. Nevertheless, the regulatory mechanism of PLK1 remains poorly understood, especially during the S and G2 phase. Here, we show that protein phosphatase 4 catalytic subunit (PPP4C) deletion causes severe female subfertility due to accumulation of DNA damage in oocytes and early embryos. PPP4C dephosphorylated PLK1 at the S137 site, negatively regulating its activity in the DSB response in early embryonic cells. Depletion of PPP4C induced sustained activity of PLK1 when cells exhibited DNA lesions that inhibited CHK2 and upregulated the activation of CDK1, resulting in inefficient loading of the essential HR factor RAD51. On the other hand, when inhibiting PLK1 in the S phase, DNA end resection was restricted. These results demonstrate that PPP4C orchestrates the switch between high-PLK1 and low-PLK1 periods, which couple the checkpoint to HR.

Clinical efficacy and immune response of neoadjuvant camrelizumab plus chemotherapy in resectable locally advanced oesophageal squamous cell carcinoma: a phase 2 trial.

BACKGROUND: Neoadjuvant immunotherapy is under intensive investigation for esophageal squamous cell carcinoma (ESCC). This study assesses the efficacy and immune response of neoadjuvant immunochemotherapy (nICT) in ESCC. METHODS: In this phase II trial (ChiCTR2100045722), locally advanced ESCC patients receiving nICT were enrolled. The primary endpoint was the pathological complete response (pCR) rate. Multiplexed immunofluorescence, RNA-seq and TCR-seq were conducted to explore the immune response underlying nICT. RESULTS: Totally 42 patients were enrolled, achieving a 27.0% pCR rate. The 1-year, 2-year DFS and OS rates were 89.2%, 64.4% and 97.3%, 89.2%, respectively. RNA-seq analysis highlighted T-cell activation as the most significantly enriched pathway. The tumour immune microenvironment (TIME) was characterised by high CD4, CD8, Foxp3, and PD-L1 levels, associating with better pathological regression (TRS0/1). TIME was categorised into immune-infiltrating, immune-tolerant, and immune-desert types. Notably, the immune-infiltrating type and tertiary lymphoid structures correlated with improved outcomes. In the context of nICT, TIM-3 negatively influenced treatment efficacy, while elevated TIGIT/PD-1 expression post-nICT correlated positively with CD8+ T cell levels. TCR-seq identified three TCR rearrangements, underscoring the specificity of T-cell responses. CONCLUSIONS: Neoadjuvant camrelizumab plus chemotherapy is effective for locally advanced, resectable ESCC, eliciting profound immune response that closely associated with clinical outcomes.

Single-cell, single-nucleus, and spatial transcriptomics characterization of the immunological landscape in the healthy and PSC human liver.

BACKGROUND & AIMS: Primary sclerosing cholangitis (PSC) is an immune-mediated cholestatic liver disease for which there is an unmet need to understand the cellular composition of the affected liver and how it underlies disease pathogenesis. We aimed to generate a comprehensive atlas of the PSC liver using multi-omic modalities and protein-based functional validation. METHODS: We employed single-cell and single-nucleus RNA sequencing (47,156 cells and 23,000 nuclei) and spatial transcriptomics (one sample by 10x Visium and five samples with Nanostring GeoMx DSP) to profile the cellular ecosystem in 10 PSC livers. Transcriptomic profiles were compared to 24 neurologically deceased donor livers (107,542 cells) and spatial transcriptomics controls, as well as 18,240 cells and 20,202 nuclei from three PBC livers. Flow cytometry was performed to validate PSC-specific differences in immune cell phenotype and function. RESULTS: PSC explants with parenchymal cirrhosis and prominent periductal fibrosis contained a population of cholangiocyte-like hepatocytes that were surrounded by diverse immune cell populations. PSC-associated biliary, mesenchymal, and endothelial populations expressed chemokine and cytokine transcripts involved in immune cell recruitment. Additionally, expanded CD4+ T cells and recruited myeloid populations in the PSC liver expressed the corresponding receptors to these chemokines and cytokines, suggesting potential recruitment. Tissue-resident macrophages, by contrast, were reduced in number and exhibited a dysfunctional and downregulated inflammatory response to lipopolysaccharide and interferon-γ stimulation. CONCLUSIONS: We present a comprehensive atlas of the PSC liver and demonstrate an exhaustion-like phenotype of myeloid cells and markers of chronic cytokine expression in late-stage PSC lesions. This atlas expands our understanding of the cellular complexity of PSC and has potential to guide the development of novel treatments. IMPACT AND IMPLICATIONS: Primary sclerosing cholangitis (PSC) is a rare liver disease characterized by chronic inflammation and irreparable damage to the bile ducts, which eventually results in liver failure. Due to a limited understanding of the underlying pathogenesis of disease, treatment options are limited. To address this, we sequenced healthy and diseased livers to compare the activity, interactions, and localization of immune and non-immune cells. This revealed that hepatocytes lining PSC scar regions co-express cholangiocyte markers, whereas immune cells infiltrate the scar lesions. Of these cells, macrophages, which typically contribute to tissue repair, were enriched in immunoregulatory genes and demonstrated a lack of responsiveness to stimulation. These cells may be involved in maintaining hepatic inflammation and could be a target for novel therapies.

The First Case of Intra-portal Islet Implantation During Liver Machine Perfusion Allowing Simultaneous Islet-liver Transplantation in A Human: A New and Safe Treatment for End-stage Liver Disease Combined With Diabetes Mellitus.

OBJECTIVE: Evaluating the safety and efficacy of implanting a liver with islet grafts into patients with end-stage liver disease and diabetes mellitus (DM). BACKGROUND: DM and end-stage liver diseases are significant health concern worldwide, often coexisting and mutually influencing each other. Addressing both diseases simultaneously is paramount. METHODS: We utilized the islet transplantation combined ischemia-free liver transplantation (ITIFLT) technique to treat a patient with hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM). The liver was procured and preserved using the ischemia-free liver transplantation (IFLT) technique, and during normothermic machine perfusion (NMP), isolated and purified islet grafts were transplanted into the liver through the portal vein. Finally, the liver, incorporating with the transplant islet grafts, was implanted into the recipient without interruption of blood supply. RESULTS: The patient received both liver and islet graft from the same donor. The patient achieved insulin-independence by post-transplant day (PTD) 9, and both liver and islet function remained robust. The patient was discharged on PTD 18 and experienced no surgical or transplantation-related complications during the follow-up period. Furthermore, islet grafts presence was observed in liver biopsies after islet transplantation. CONCLUSIONS: This landmark case marks the inaugural application of ITIFLT in humans, signifying its potential as a promising treatment modality for end-stage liver disease with DM.

Combination treatment with ferroptosis and autophagy inducers significantly inhibit the proliferation and migration of oral squamous cell carcinoma.

Oral squamous cell carcinoma (OSCC), a malignancy originating from mucosal epithelial cells. Currently, triggering apoptotic cell death with anticancer drugs is the main way to inhibit OSCC cells. However, the capability to trigger apoptosis in tumors is constrained by the intrinsic resistance of tumor cells to apoptosis, hampering its effectiveness. Thus, utilizing alternative modes of non-apoptotic cell death offers new therapeutic possibilities, such as using a drug combination strategy to simultaneously induce ferroptosis and autophagy has the potential to improve OSCC therapy. In this study, we found the ferroptosis inducer RSL3 has certain inhibitory effects on the proliferation and migration of OSCC cells. Interestingly, our studies showed that RSL3 is also associated with autophagy activation. Based on this finding, we tried to combine RSL3 with the autophagy inducer LYN-1604 to improve the therapeutic effect. The results demonstrated that simultaneous regulation of autophagy and ferroptosis significantly reduced the proliferation and migration of OSCC cells. Taken together, we demonstrated the therapeutic potential of RSL3 in OSCC cells and proposed that simultaneous activation of autophagy and ferroptosis have synergistic effects, which would provide valuable clues for further exploration of targeted therapy for OSCC.

Efficient Tin Perovskite Solar Cells via Suppressing Autoxidation in Inert Atmosphere.

The unsatisfactory power conversion efficiency (PCE) and long-term stability of tin perovskite solar cells (TPSCs) restrict its further development as alternatives to lead perovskite solar cells (LPSCs). Considerable research has focused on the negative impacts of O2 and H2 O, while discussions about degradation mechanism in an inert atmosphere remains insufficient. Herein, the light-induced autoxidation of tin perovskite in nitrogen atmosphere is revealed for the first time and the elastic lattice distortion is demonstrated as the crucial role of rapid degradation. The continuous injection of photons induces energy transfer from excited A-site cations to vibrating Sn-I framework, leading to the elastic deformation of perovskite lattice. Consequently, the over distorted Sn-I framework releases free iodine and further oxidizes Sn2+ in the form of molecular iodine. Through an appropriately designed light-dark cyclic test, a remarkable PCE of 14.41% is achieved based on (Cs0.025 (MA0.25 FA0.75 )0.975 ) 0.98 EDA0.01 SnI3 solar cells, which is the record of hybrid triple TPSCs so far. The findings unveil autoxidation as the crux of TPSCs' degradation in an inert atmosphere and suggest the possibility of reinforcing the tin perovskite lattice towards highly efficient and stable TPSCs.

Mitigating Surface Defects in Tin-Based Perovskite Films with α-Tocopherol for Enhanced Photovoltaic Performance.

Surface defects in tin-based perovskite films disrupt the periodic arrangement of atoms in crystals, making surface atoms more susceptible to interactions with water and oxygen molecules in the surrounding environment. The diffusion of oxygen ions into the perovskite interior leads to the formation of severe bulk defects, which compromises the performance of tin-based perovskite solar cells (PSCs). As a result, surface defects are recognized as the primary source of degradation and require special attention. In this study, α-Tocopherol (also known as vitamin E) into tin-based perovskite films is introduced. Experimental results show that because of its larger volume, α-Tocopherol does not enter the perovskite lattice. Instead, it forms van der Waals and hydrogen bond interactions with the formamidine ion (FA+) and the [SnI6]4- octahedron at the perovskite terminals. Through α-Tocopherol passivation, both surface and interior oxidation of the perovskite are significantly suppressed as α-Tocopherol firmly embeds itself on the perovskite surface. Density functional theory analysis confirms the inhibition of I─Sn antisite defects (ISn) and Sn interstitial defects (Sni), which possess deep trap states within the bandgap. Ultimately, it is demonstrated that α-Tocopherol enhances the power conversion efficiency (PCE) from 9.19% to 13.14% and prolongs the lifetime of tin-based PSCs to over 50 days.

Interleukin-6 trans-signaling regulates monocyte chemoattractant protein-1 production in immune-mediated necrotizing myopathy.

OBJECTIVE: Immune-mediated necrotizing myopathy (IMNM) is pathologically characterized by diffuse myofiber necrosis and regeneration, myophagocytosis, and a sparse inflammatory infiltrate. The monocyte chemoattractant protein-1 (MCP-1) is a key chemokine that regulates monocyte/macrophage infiltration into injured tissues. The interleukin-6 (IL-6) signalling in the induction of MCP-1 expression has not been investigated in IMNM. METHODS: MCP-1 expression in muscle specimens was assessed using immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR). Levels of multiple serological cytokines were evaluated using the Meso Scale Discovery electrochemiluminescence system. Flow cytometry, RT-qPCR, enzyme-linked immunosorbent assay, western blot, dual-luciferase reporter assays, and chromatin immunoprecipitation-qPCR were performed to explore the effects of IL-6 signalling on MCP-1 production in human myoblasts. RESULTS: MCP-1 was scattered and was positively expressed within myofibers and a few inflammatory cells in the muscles of patients with IMNM. Sarcoplasmic MCP-1 expression significantly correlated with myonecrosis, myoregeneration, and inflammatory infiltration. Serum MCP-1, IL-6, and the soluble form of the IL-6 receptor (sIL-6R) were elevated in patients with IMNM compared with controls. Serological MCP-1 levels were significantly associated with serum IL-6 expression and clinical disease severity in IMNM patients. The IL-6/sIL-6R complex induced MCP-1 expression via the signal transducer and activator of transcription 3 (STAT3) pathway in human myoblasts. Mechanistically, phospho-STAT3 was enriched in the MCP-1 promoter region and promoted the transcription. CONCLUSION: IL-6 trans-signalling may contribute to the immunopathogenesis of IMNM by augmenting inflammation through regulation of MCP-1 expression in IMNM.

The lncRNA LINC01605 promotes the progression of pancreatic ductal adenocarcinoma by activating the mTOR signaling pathway.

BACKGROUND: This study investigated the molecular mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in the process of tumor growth and liver metastasis of pancreatic ductal adenocarcinoma (PDAC). METHODS: LINC01605 was filtered out with specificity through TCGA datasets (related to DFS) and our RNA-sequencing data of PDAC tissue samples from Renji Hospital. The expression level and clinical relevance of LINC01605 were then verified in clinical cohorts and samples by immunohistochemical staining assay and survival analysis. Loss- and gain-of-function experiments were performed to estimate the regulatory effects of LINC01605 in vitro. RNA-seq of LINC01605-knockdown PDAC cells and subsequent inhibitor-based cellular function, western blotting, immunofluorescence and rescue experiments were conducted to explore the mechanisms by which LINC01605 regulates the behaviors of PDAC tumor cells. Subcutaneous xenograft models and intrasplenic liver metastasis models were employed to study its role in PDAC tumor growth and liver metastasis in vivo. RESULTS: LINC01605 expression is upregulated in both PDAC primary tumor and liver metastasis tissues and correlates with poor clinical prognosis. Loss and gain of function experiments in cells demonstrated that LINC01605 promotes the proliferation and migration of PDAC cells in vitro. In subsequent verification experiments, we found that LINC01605 contributes to PDAC progression through cholesterol metabolism regulation in a LIN28B-interacting manner by activating the mTOR signaling pathway. Furthermore, the animal models showed that LINC01605 facilitates the proliferation and metastatic invasion of PDAC cells in vivo. CONCLUSIONS: Our results indicate that the upregulated lncRNA LINC01605 promotes PDAC tumor cell proliferation and migration by regulating cholesterol metabolism via activation of the mTOR signaling pathway in a LIN28B-interacting manner. These findings provide new insight into the role of LINC01605 in PDAC tumor growth and liver metastasis as well as its value for clinical approaches as a metabolic therapeutic target in PDAC.

Lithium Exposure and Risk of Major Neurocognitive Disorders: A Systematic Review and Meta-analysis.

BACKGROUND: Published studies on the association between lithium use and the decreased risk of major neurocognitive disorders (MNCDs) have shown disparities in their conclusions. We aimed to provide updated evidence of this association. METHODS: A comprehensive literature search was performed in PubMed, EMBASE, and Cochrane Library from inception until August 31, 2023. All the observational studies evaluating the association between lithium use and MNCD risk were eligible for inclusion. Pooled odds ratios (ORs) and 95% prediction intervals were computed using random-effects models. RESULTS: Eight studies with 377,060 subjects were included in the analysis. In the general population on the association between lithium use versus nonuse and dementia, the OR was 0.94 (95% confidence interval [CI] = 0.77-1.24). Further analysis also demonstrated that lithium use was not associated with an increased risk of Alzheimer's disease (OR = 0.69, 95% CI: 0.31-1.65). When the analysis was restricted to individuals with bipolar disorder to reduce the confounding by clinical indication, lithium exposure was also not associated with a decreased risk of MNCD (OR = 0.9, 95% CI = 0.71-1.15). CONCLUSION: The results of this systematic review and meta-analysis do not support a significant association between lithium use and the risk of MNCD.

SUMOylation at the crossroads of gut health: insights into physiology and pathology.

SUMOylation, a post-translational modification involving the covalent attachment of small ubiquitin-like modifier (SUMO) proteins to target substrates, plays a pivotal role at the intersection of gut health and disease, influencing various aspects of intestinal physiology and pathology. This review provides a comprehensive examination of SUMOylation's diverse roles within the gut microenvironment. We examine its critical roles in maintaining epithelial barrier integrity, regulating immune responses, and mediating host-microbe interactions, thereby highlighting the complex molecular mechanisms that underpin gut homeostasis. Furthermore, we explore the impact of SUMOylation dysregulation in various intestinal disorders, including inflammatory bowel diseases and colorectal cancer, highlighting its implications as a potential diagnostic biomarker and therapeutic target. By integrating current research findings, this review offers valuable insights into the dynamic interplay between SUMOylation and gut health, paving the way for novel therapeutic strategies aimed at restoring intestinal equilibrium and combating associated pathologies.

Halospeciosus flavus gen. nov., sp. nov. and Haladaptatus caseinilyticus sp. nov., halophilic archaea isolated from saline soil of an inland solar saltern and offshore sediment.

Two novel halophilic archaeal strains (XZGYJ-43T and ZJ1T) were isolated from Mangkang ancient solar saltern (Tibet, PR China) and Zhujiang river inlet (Guangdong, PR China), respectively. The comparison of the 16S rRNA gene sequences revealed that strain XZGYJ-43T is related to the current species of the family Halobacteriaceae (89.2-91.7% similarity) and strain ZJ1T showed 94.7-98.3% similarity to the current species of the genus Haladaptatus. Phylogenetic analyses based on 16S rRNA genes, rpoB' genes and genomes indicated that strain XZGYJ-43T is separate from the related genera, Halocalculus, Salarchaeum and Halarchaeum of the family Halobacteriaceae, and strain ZJ1T tightly clusters with the current species of the genus Haladaptatus. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values between strain XZGYJ-43T and the current species of the family Halobacteriaceae were 71-75, 20-25 and 59-68 %, and these values between strain ZJ1T and the current species of the genus Haladaptatus were 77-81, 27-32 and 76-82 %, respectively, clearly below the thresholds for prokaryotic species demarcation. These two strains could be distinguished from their relatives according to differential phenotypic characteristics. The major polar lipids of strain XZGYJ-43T were phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me), mannosyl glucosyl diether (DGD-1; DGD-PA) and sulphated mannosyl glucosyl diether (S-DGD-1; S-DGD-PA), and those of strain ZJ1T were PA, PG, PGP-Me, DGD-PA, S-DGD-1 (S-DGD-PA) and sulphated galactosyl mannosyl glucosyl diether. Based on phenotypic, phylogenetic and genomic data, strain XZGYJ-43T (=CGMCC 1.13890T=JCM 33735T) represents a novel species of a new genus within the family Halobacteriaceae, and strain ZJ1T (=CGMCC 1.18785T=JCM 34917T) represents a novel species of the genus Haladaptatus, for which the names Halospeciosus flavus gen. nov., sp. nov. and Haladaptatus caseinilyticus sp. nov. are proposed, respectively.

Halomicrococcus gelatinilyticus sp. nov. and Halosimplex aquaticum sp. nov., halophilic archaea isolated from saline soil and an inland solar saltern.

Two extremely halophilic archaeal strains, GSLN9T and XZYJT29T, were isolated from the saline soil in different regions of western China. Both strains GSLN9T and XZYJT29T have two 16S rRNA genes with similarities of 95.1 and 94.8 %, respectively. Strain GSLN9T was mostly related to the genus Halomicrococcus based on 16S rRNA (showing 91.0-96.0 % identities) and rpoB' genes (showing 92.0 % identity). Strain XZYJT29T showed 92.1-97.6 % (16S rRNA gene) and 91.4-93.1 % (rpoB' gene) sequence similarities to its relatives in the genus Halosimplex, respectively. The polar lipid profile of strain GSLN9T included phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me), phosphatidylglycerol sulphate (PGS), sulphated mannosyl glucosyl diether (S-DGD-1) and sulphated galactosyl mannosyl glucosyl diether (S-TGD-1), mostly similar to that of Halomicrococcus hydrotolerans H22T. PA, PG, PGP-Me, S-DGD-1 (S-DGD-PA), S2-DGD, S-TGD-1 and an unidentified glycolipid were detected in strain XZYJT29T; this polar lipid composition is similar to those of members of the genus Halosimplex. The average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity values between these two strains and their relatives of the genera Halomicrococcus and Halosimplex were no more than 82, 27 and 80 %, respectively, much lower than the thresholds for species demarcation. Other phenotypic characterization results indicated that strains GSLN9T and XZYJT29T can be differentiated from the current species of the genera Halomicrococcus and Halosimplex, respectively. These results revealed that strains GSLN9T (=CGMCC 1.15215T=JCM 30842T) and XZYJT29T (=CGMCC 1.15828T=JCM 31853T) represent novel species of Halomicrococcus and Halosimplex, for which the names Halomicrococcus gelatinilyticus sp. nov. and Halosimplex aquaticum sp. nov. are proposed.

Genome-based taxonomy of genera Haloarcula and Halomicroarcula, and description of six novel species of Haloarcula.

The genera Haloarcula and Halomicroarcula are the most closely related genera within the family Haloarculaceae (class Halobacteria). The respective 16S rRNA genes of type strains from the genus Haloarcula showed 94.7-96.5% similarities to their homologous genes of type strains from the genus Halomicroarcula. The Haloarcula species showed 89.3-92.8% rpoB' gene similarities to Halomicroarcula species. These similarities were higher than the proposed genus boundary. Phylogenomic analysis revealed that these two genera formed a tight cluster separated from Halomicrobium with high bootstrap confidence. The average amino acid identity (AAI) values among Haloarcula and Halomicroarcula were 70.1-74.5%, higher than the cutoff value (67.0%) to differentiate the genera Haloarcula and Halomicroarcula from Halomicrobium. These results indicated that the genus Halomicroarcula should be merged with Haloarcula. Then, six novel species are described based on strains DFY41T, GDY20T, SHR3T, XH51T, YJ-61-ST, and ZS-22-S1T isolated from coarse sea salt, marine solar saltern, and salt lake (China). These six strains formed separate clades (90.1-99.3% 16S rRNA and 89.0-94.9% rpoB' gene similarities) and then clustered with current Haloarcula and Halomicroarcula species (89.4-99.1% 16S rRNA and 87.6-95.0% rpoB' gene similarities), as revealed by phylogenetic analyses. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), and AAI values among these six strains and current Haloarcula and Halomicroarcula species were 76.2-89.8%, 25.3-46.0%, and 70.3-89.7%, respectively, clearly below the species demarcation threshold. These six strains were distinguished from current Haloarcula and Halomicroarcula species according to differential phenotypic characteristics. Six novel species, Haloarcula halophila sp. nov., Haloarcula litorea sp. nov., Haloarcula rara sp. nov., Haloarcula halobia sp. nov., Haloarcula pelagica sp. nov., and Haloarcula ordinaria sp. nov., are proposed to accommodate strains DFY41T, GDY20T, SHR3T, XH51T, YJ-61-ST, and ZS-22-S1T, respectively.

Halobacterium yunchengense sp. nov., Natronomonas amylolytica sp. nov., Halorientalis halophila sp. nov., Halobellus salinisoli sp. nov., halophilic archaea isolated from a saline lake and inland saline soil.

Four halophilic archaeal strains YCN1T, YCN58T, LT38T, and LT62T were isolated from Yuncheng Salt Lake (Shanxi, China) and Tarim Basin (Xinjiang, China), respectively. Phylogenetic and phylogenomic analyses showed that these four strains tightly cluster with related species of Halobacterium, Natronomonas, Halorientalis, and Halobellus, respectively. The AAI, ANI, and dDDH values between these four strains and their related species of respective genera were lower than the proposed threshold values for species delineation. Strains YCN1T, YCN58T, LT38T, and LT62T could be differentiated from the current species of Halobacterium, Natronomonas, Halorientalis, and Halobellus, respectively, based on the comparison of diverse phenotypic characteristics. The polar lipid profiles of these four strains were closely similar to those of respective relatives within the genera Halobacterium, Natronomonas, Halorientalis, and Halobellus, respectively. The phenotypic, phylogenetic, and genome-based analyses indicated that strains YCN1T, YCN58T, LT38T, and LT62T represent respective novel species within the genera Halobacterium, Natronomonas, Halorentalis, and Halobellus, for which the names Halobacterium yunchengense sp. nov., Natronomonas amylolytica sp. nov., Halorientalis halophila sp. nov., and Halobellus salinisoli sp. nov. are proposed, respectively.

Preoperative and intraoperative tirofiban during endovascular thrombectomy in large vessel occlusion stroke due to large artery atherosclerosis.

BACKGROUND AND PURPOSE: The aim of this study is to investigate the efficacy and safety of preoperative versus intraoperative tirofiban in patients with large vessel occlusion (LVO) due to large artery atherosclerosis (LAA). METHODS: This is a retrospective multicenter cohort study based on the RESCUE-RE (Registration Study for Critical Care of Acute Ischemic Stroke After Recanalization) trial enrolling patients with anterior circulation LVO classified as LAA within 24 h of onset. Patients were divided into three groups: preoperative tirofiban (PT), intraoperative tirofiban (IT), and no tirofiban (NT). Propensity score matching (PSM) was used to balance baseline characteristics. The efficacy outcomes included 90-day functional independence (modified Rankin Scale score = 0-2) and early partial recanalization (EPR; defined as a modified Thrombolysis in Cerebral Infarction score = 1-2a). The safety outcomes included symptomatic intracranial hemorrhage (sICH). RESULTS: A total of 104 matched triplets were obtained through PSM. Compared with NT, PT increased 90-day functional independence (60.8% vs. 42.3%, p = 0.008) and EPR (42.7% vs. 18.3%, p < 0.001) rate, with a tendency to increase the asymptomatic intracranial hemorrhage (aICH) proportion (28.8% vs. 18.3%, p = 0.072). Compared with IT, PT had a higher 90-day functional independence (60.8% vs. 45.2%, p = 0.025) and EPR (42.7% vs. 20.2%, p = 0.001) rate, with no significant difference in sICH (14.4% vs. 7.7%, p = 0.122) and aICH (28.8% vs. 21.2%, p = 0.200). Compared with NT, IT had a lower 90-day mortality rate (9.6% vs. 24.0%, p = 0.005). CONCLUSIONS: Tirofiban shows good adjuvant therapy potential in acute ischemic stroke-LVO due to LAA patients. PT is associated with higher rates of EPR and better therapeutic efficacy. In addition, EPR may be a potential way to improve prognosis.

Short segment myelitis as a dominant manifestation of cryptococcal infection: a case report.

Cryptococcal infection of central nervous system commonly involves meningitis or meningoencephalitis, but rarely mimics inflammatory myelitis. We present short segment myelitis as a dominant manifestation caused by Cryptococcus neoformans in a patient with nephrotic syndrome under immunosuppressive therapy. This case report highlights Cryptococcus neoformans as a potential etiological factor for short segment myelitis in immunocompromised hosts.

Photocatalytic Reduction of Perrhenate and Pertechnetate in a Strongly Acidic Aqueous Solution.

Pertechnetate (99TcO4-), a physiologically toxic radioactive anion, is of great concern due to its high mobility in environmental contamination remediation. Although the soluble oxyanion can be photoreduced to sparingly soluble TcO2·nH2O, its effective removal from a strongly acidic aqueous solution remains a challenge. Here, we found that low-crystalline nitrogen-doped titanium oxide (N-TiO2, 0.6 g L-1) could effectively uptake perrhenate (ReO4-, 10 mg L-1, a nonradioactive surrogate for TcO4-) with 50.8% during 360 min under simulated sunlight irradiation at pH 1.0, but P25 and anatase could not. The nitrogen active center formed by trace nitrogen doping in N-TiO2 can promote the separation and transfer of photogenerated carriers. The positive valence band value of N-TiO2 is slightly higher than those of P25 and anatase, which means that the photogenerated holes have a stronger oxidizability. These holes are involved in the formation of strong reducing •CO2- radicals from formic acid oxidation. The active radicals convert ReO4- to Re(VI), which is subsequently disproportionated to Re(IV) and Re(VII). Effective photocatalytic reduction/removal of Re(VII)/Tc(VII) is performed on the material, which may be considered a potential and convenient strategy for technetium decontamination and extraction in a strongly acidic aqueous solution.

Glutathione Modified silicon-doped Carbon Quantum dots as a Sensitive Fluorescent Probe for ClO- Detection.

A selective and sensitive fluorescence method for hypochlorite (ClO-) was designed using glutathione (GSH) modified silicon-doped carbon quantum dots (GSH@Si-CDs). Then a dual emission ratio fluorescence probe (RF-probe) was obtained based on carbodiimide-activated coupling reaction between GSH and Si-CDs. i.e., when the excitation wavelength was kept at 360 nm, the GSH@Si-CDs exhibited strong blue and weak yellow fluorescence at 430 and 580 nm. Meanwhile, the fluorescence of GSH@Si-CDs could be selectively quenched at 430 nm and enhanced at 580 nm in the presence of ClO-, and corresponding limit of detection (LOD) and linear range were measured to be 0.35 µM and 1.0-33.3 µM. The sensing mechanism of the system was also investigated in detail. Moreover, the RF-probe with good accuracy was successfully employed to monitor ClO- in real samples with satisfactory results compared to the standard iodometric method.

Theoretical study on the photophysical properties of thiophene-fused-type BODIPY series molecules in fluorescence imaging and photodynamic therapy.

As a class of photosensitizers (PSs) with dual functions of photodynamic therapy (PDT) and fluorescence imaging, the relationship between the structure and dual-function of thiophene-fused-type BODIPY dyes has not been studied in depth before. We found that the thiophene-fused-type BODIPY triplet photosensitizer is produced according to the energy level matching rule and the introduction of the thiophene ring significantly reduces the energy gap ΔEST between singlet and triplet states, as revealed by our investigation of the excited state structures and energies of thieno-fused BODIPY dyes. At the same time, a tiny ΔEST also results in a greatly enhanced intersystem crossing (ISC) rate, kISC. The kISC value of MeO-BODIPY, having the highest singlet oxygen quantum yield (ΦΔ), is the largest. Substitution with a strong electron donor N,N-dimethylaminophenyl (DMA) leads to the vertical configuration in the T1 state. The small ΔE (0.0029 eV) between the HOMO and HOMO-1 triggers the photo induced electron transfer (PET) of inhibiting ISC and fluorescence. When thieno-fused BODIPYs react with pyrrole, the increase of π-conjugation and smaller ΔEHOMO-LUMO explain the redshift in emission wavelength of thieno-pyrrole-fused BODIPY. The more planar configuration of the S1 state and the stronger oscillator intensity reflect a higher fluorescence quantum yield (ΦF). The extension of π-conjugation can cause molecules to transition to higher-level singlet excited states (Sn states, n ≥ 1) after absorbing energy and reduce the energy level of the excited state, resulting in multiple channels and favoring 1O2 production for thieno-pyrrole-fused BODIPYs with electron-withdrawing groups at the para-position of the phenyl groups. Due to ΔES0-T1 < 0.980 eV, the substitution of electron-donating groups cannot produce 1O2. In this work, we have revealed the mechanism of ISC and the fluorescence emission process in the thiophene-fused-type BODIPY dye, which has provided a theoretical foundation and guidance for the future design of BODIPY-based heavy-atom-free PSs for molecular applications in PDT.