GSDME-mediated Pyroptosis Contributes to Chemotherapy-induced Platelet Hyperactivity and Thrombotic Potential.

Thrombotic complications due to platelet hyperreactivity are a major cause of death in patients undergoing chemotherapy. However, the underlying mechanisms are not fully understood. Herein, using human and GSDME-/- mouse platelets, we showed that GSDME is functionally expressed in anucleate platelets and GSDME-mediated pyroptosis, a newly identified form of cell death in mammalian nucleated cells, contributes to platelet hyperactivity in cisplatin-based chemotherapy. Cisplatin or etoposide activates caspase-3 to cleave GSDME, thereby releasing the N-terminal fragment of GSDME (GSDME-N) toward the platelet plasma membrane, subsequently forming membrane pores and facilitating platelet granule release. This eventually promotes platelet hyperactivity and thrombotic potential. We identified flotillin-2, a scaffold protein, as a GSDME-N interactor that recruits GSDME-N to the platelet membrane. loss of GSDME protects mice from cisplatin-induced platelet hyperactivity. Our results provide evidence that targeting GSDME-mediated pyroptosis could reduce thrombotic potential in chemotherapy.

Transcription factor EB coordinates environmental cues to regulate T regulatory cells' mitochondrial fitness and function.

T regulatory (Treg) cells are essential for self-tolerance whereas they are detrimental for dampening the host anti-tumor immunity. How Treg cells adapt to environmental signals to orchestrate their homeostasis and functions remains poorly understood. Here, we identified that transcription factor EB (TFEB) is induced by host nutrition deprivation or interleukin (IL)-2 in CD4+ T cells. The loss of TFEB in Treg cells leads to reduced Treg accumulation and impaired Treg function in mouse models of cancer and autoimmune disease. TFEB intrinsically regulates genes involved in Treg cell differentiation and mitochondria function while it suppresses expression of proinflammatory cytokines independently of its established roles in autophagy. This coordinated action is required for mitochondria integrity and appropriate lipid metabolism in Treg cells. These findings identify TFEB as a critical regulator for orchestrating Treg generation and function, which may contribute to the adaptive responses of T cells to local environmental cues.

Time Division Colorful Multiplexing Based on Carbon Nanodots with Modifiable Colors and Lifetimes.

Optical multiplexing technology plays a crucial role in various fields such as data storage, anti-counterfeiting, and time-resolved biological imaging. Nevertheless, employing single-wavelength phosphorescence for multiplexing often results in spectral overlap among the emission peaks of various channels, which can precipitate crosstalk and misinterpretation in the information-decoding process, thereby compromising the integrity and precision of the encrypted data. This paper proposes a time-divided colorful multiplexing technology based on phosphorescent carbon nanodots with different colors and lifetimes. Using different luminescence colors to symbolize varying information levels helps achieve multitiered information encryption and storage. By modulation of the lifetime and the emission wavelength, intricate information can be encoded, thereby enhancing the intricacy and security of the encryption mechanism. By assigning different data bits to each color, more information can be encoded in the same physical space. This method enables higher-density information storage and fortifies encryption, ensuring the compactness and security of information.

Uropathogenic Escherichia coli Subverts Host Autophagic Defenses by Stalling Preautophagosomal Structures to Escape Lysosome Exocytosis.

Urinary tract infections are primarily caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles and escapes into the cytosol by disrupting fusiform vesicle membrane using outer membrane phospholipase PldA, and establishes biofilm-like intracellular bacterial communities (IBCs) for protection from host immune clearance. Cytosolic UPEC is captured by autophagy to form autophagosomes, then transported to lysosomes, triggering the spontaneous exocytosis of lysosomes. The mechanism by which UPEC evades autophagy to recognize and form IBCs remains unclear. Here, we demonstrate that by inhibiting autophagic flux, UPEC PldA reduces the lysosome exocytosis of BECs. By reducing intracellular phosphatidylinositol 3-phosphate levels, UPEC PldA increases the accumulation of NDP52 granules and decreases the targeting of NDP52 to autophagy, hence stalling preautophagosome structures. Thus, our results uncover a critical role for PldA to inhibit autophagic flux, favoring UPEC escapes from lysosome exocytosis, thereby contributing to acute urinary tract infection.

Different metazoan parasites, different transcriptomic responses, with new insights on parasitic castration by digenetic trematodes in the schistosome vector snail Biomphalaria glabrata.

BACKGROUND: Gastropods of the genus Biomphalaria (Family Planorbidae) are exploited as vectors by Schistosoma mansoni, the most common causative agent of human intestinal schistosomiasis. Using improved genomic resources, overviews of how Biomphalaria responds to S. mansoni and other metazoan parasites can provide unique insights into the reproductive, immune, and other systems of invertebrate hosts, and their responses to parasite challenges. RESULTS: Using Illumina-based RNA-Seq, we compared the responses of iM line B. glabrata at 2, 8, and 40 days post-infection (dpi) to single infections with S. mansoni, Echinostoma paraensei (both digenetic trematodes) or Daubaylia potomaca (a nematode parasite of planorbid snails). Responses were compared to unexposed time-matched control snails. We observed: (1) each parasite provoked a distinctive response with a predominance of down-regulated snail genes at all time points following exposure to either trematode, and of up-regulated genes at 8 and especially 40dpi following nematode exposure; (2) At 2 and 8dpi with either trematode, several snail genes associated with gametogenesis (particularly spermatogenesis) were down-regulated. Regarding the phenomenon of trematode-mediated parasitic castration in molluscs, we define for the first time a complement of host genes that are targeted, as early as 2dpi when trematode larvae are still small; (3) Differential gene expression of snails with trematode infection at 40dpi, when snails were shedding cercariae, was unexpectedly modest and revealed down-regulation of genes involved in the production of egg mass proteins and peptide processing; and (4) surprisingly, D. potomaca provoked up-regulation at 40dpi of many of the reproduction-related snail genes noted to be down-regulated at 2 and 8dpi following trematode infection. Happening at a time when B. glabrata began to succumb to D. potomaca, we hypothesize this response represents an unexpected form of fecundity compensation. We also document expression patterns for other Biomphalaria gene families, including fibrinogen domain-containing proteins (FReDs), C-type lectins, G-protein coupled receptors, biomphalysins, and protease and protease inhibitors. CONCLUSIONS: Our study is relevant in identifying several genes involved in reproduction that are targeted by parasites in the vector snail B. glabrata and that might be amenable to manipulation to minimize their ability to serve as vectors of schistosomes.

Nitrogen-Mediated Promotion of Cobalt-Based Oxygen Evolution Catalyst for Practical Anion-Exchange Membrane Electrolysis.

Scarce and expensive iridium oxide is still the cornerstone catalyst of polymer-electrolyte membrane electrolyzers for green hydrogen production because of its exceptional stability under industrially relevant oxygen evolution reaction (OER) conditions. Earth-abundant transition metal oxides used for this task, however, show poor long-term stability. We demonstrate here the use of nitrogen-doped cobalt oxide as an effective iridium substitute. The catalyst exhibits a low overpotential of 240 mV at 10 mA cm-2 and negligible activity decay after 1000 h of operation in an alkaline electrolyte. Incorporation of nitrogen dopants not only triggers the OER mechanism switched from the traditional adsorbate evolution route to the lattice oxygen oxidation route but also achieves oxygen nonbonding (ONB) states as electron donors, thereby preventing structural destabilization. In a practical anion-exchange membrane water electrolyzer, this catalyst at anode delivers a current density of 1000 mA cm-2 at 1.78 V and an electrical efficiency of 47.8 kW-hours per kilogram hydrogen.

The risk of treatment-related toxicities with PD-1/PD-L1 inhibitors in patients with lung cancer.

The risk of treatment-related toxicities with programmed cell death 1 and its ligand (PD-1/PD-L1) inhibitors in patients with lung cancer is unclear and inconclusive. PubMed, EMBASE, and the Cochrane Library databases were systematically searched without language restrictions from inception to May 31, 2024 to identify Phase 3 randomized controlled trials of lung cancer comparing PD-1/PD-L1 inhibitors versus placebo/best supportive care (alone or in combination with nontargeted chemotherapy) that had available data regarding treatment-related adverse events (TRAEs) or incidence and sample size. Random-effect models were employed to study the pooled relative risk (RR) and 95% confidence intervals (CIs). Finally, 36 trials, involving 19,693 participants, fulfilled the inclusion criteria. PD-1/PD-L1 inhibitors significantly augmented the likelihood of developing all-grade (RR, 1.03; 95% CI, 1.01-1.04, p < .01) and grade ≥3 TRAEs (RR, 1.16; 95% CI, 1.10 to 1.23, p < .01). PD-1/PD-L1 inhibitors substantially augmented the odds of developing treatment-related serious adverse events (SAEs) (RR, 1.48; 95% CI, 1.27-1.71, p < .01) and fatal adverse events (FAEs) (RR, 1.42; 95% CI, 1.11-1.82, p < .01). Subgroup analyses indicated that the RR of SAEs and FAEs were generally consistent, regardless of treatment type, tumor type, treatment setting, PD-1/PD-L1 inhibitors type and study design. The most common causes of FAEs were respiratory failure/insufficiency (33.3%), cardiac events (16.1%), and hematological disorders (10.1%). We demonstrated that PD-1/PD-L1 inhibitors were significantly correlated with higher possibility of developing treatment-related toxicities, especially SAEs and FAEs, compared with placebo/best supportive care controls.

Z-Scheme Heterojunction of Hierarchical Cu2S/CdIn2S4 Hollow Cubes to Boost Photoelectrochemical Performance.

The exaltation of light-harvesting efficiency and the inhibition of fast charge recombination are pivotal to the improvement of photoelectrochemical (PEC) performance. Herein, a direct Z-scheme heterojunction is designed of Cu2S/CdIn2S4 by in situ growth of CdIn2S4 nanosheets on the surface of hollow CuS cubes and then annealing at 400 °C. The constructed Z-scheme heterojunction is demonstrated with electron paramagnetic resonance and redox couple (p-nitrophenol/p-aminophenol) measurements. Under illumination, it shows the photocurrent 6 times larger than that of hollow Cu2S cubes, and affords outstanding PEC performance over the known Cu2S and CdIn2S4-based photocatalysts. X-ray photoelectron spectroscopy and density functional theory results demonstrate a strong internal electric field formed in Cu2S/CdIn2S4 Z-scheme heterojunction, which accelerates the Z-scheme charge migration, thereby promoting electron-hole separation and enhancing their utilization efficiency. Moreover, the hollow structure of Cu2S is conducive to shortening the charge transport distance and improving light-harvesting capability. In proof-of-concept PEC application, a PEC detection method for miRNA-141 based on the sensitivity of benzo-4-chloro-hexadienone to light absorption on Cu2S/CdIn2S4 modified electrode is developed with good selectivity and a limit of detection of 32 aM. This work provides a simple approach for designing photoactive materials with highly efficient PEC performance.

Protein tyrosine phosphatase PTPN22 negatively modulates platelet function and thrombus formation.

Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) is a protein tyrosine phosphatase that negatively regulates T-cell signaling. However, whether it is expressed and functions in platelets remains unknown. Here we investigated the expression and role of PTPN22 in platelet function. We reported PTPN22 expression in both human and mouse platelets. Using PTPN22-/- mice, we showed that PTPN22 deficiency significantly shortened tail-bleeding time and accelerated arterial thrombus formation without affecting venous thrombosis and the coagulation factors VIII and IX. Consistently, PTPN22-deficient platelets exhibited enhanced platelet aggregation, granule secretion, calcium mobilization, lamellipodia formation, spreading, and clot retraction. Quantitative phosphoproteomic analysis revealed the significant difference of phosphodiesterase 5A (PDE5A) phosphorylation in PTPN22-deficient platelets compared with wild-type platelets after collagen-related peptide stimulation, which was confirmed by increased PDE5A phosphorylation (Ser92) in collagen-related peptide-treated PTPN22-deficient platelets, concomitant with reduced level and vasodilator-stimulated phosphoprotein phosphorylation (Ser157/239). In addition, PTPN22 interacted with phosphorylated PDE5A (Ser92) and dephosphorylated it in activated platelets. Moreover, purified PTPN22 but not the mutant form (C227S) possesses intrinsic serine phosphatase activity. Furthermore, inhibition of PTPN22 enhanced human platelet aggregation, spreading, clot retraction, and increased PDE5A phosphorylation (Ser92). In conclusion, our study shows a novel role of PTPN22 in platelet function and arterial thrombosis, identifying new potential targets for future prevention of thrombotic or cardiovascular diseases.

Enhancing therapeutic efficacy in luminal androgen receptor triple-negative breast cancer: exploring chidamide and enzalutamide as a promising combination strategy.

Extensive exploration of the molecular subtypes of triple-negative breast cancer (TNBC) is critical for advancing precision medicine. Notably, the luminal androgen receptor (LAR) subtype has attracted attention for targeted treatment combining androgen receptor antagonists and CDK4/6 inhibitors. Unfortunately, this strategy has proven to be of limited efficacy, highlighting the need for further optimization. Using our center's comprehensive multiomics dataset (n = 465), we identified novel therapeutic targets and evaluated their efficacy through multiple models, including in vitro LAR cell lines, in vivo cell-derived allograft models and ex vivo patient-derived organoids. Moreover, we conducted flow cytometry and RNA-seq analysis to unveil potential mechanisms underlying the regulation of tumor progression by these therapeutic strategies. LAR breast cancer cells exhibited sensitivity to chidamide and enzalutamide individually, with a drug combination assay revealing their synergistic effect. Crucially, this synergistic effect was verified through in vivo allograft models and patient-derived organoids. Furthermore, transcriptomic analysis demonstrated that the combination therapeutic strategy could inhibit tumor progression by regulating metabolism and autophagy. This study confirmed that the combination of histone deacetylase (HDAC) inhibitors and androgen receptor (AR) antagonists possessed greater therapeutic efficacy than monotherapy in LAR TNBC. This finding significantly bolsters the theoretical basis for the clinical translation of this combination therapy and provides an innovative strategy for the targeted treatment of LAR TNBC.

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.

BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

Placebo and Nocebo Responses in Pharmacological Trials of Tic Disorders: A Meta-Analysis.

BACKGROUND: Clinical trials of new drugs for tic disorders (TD) often fail to yield positive results. Placebo and nocebo responses play a vital role in interpreting the outcomes of randomized controlled trials (RCTs), yet these responses in RCTs of TD remain unexplored. OBJECTIVE: The aim was to assess the magnitude of placebo and nocebo responses in RCTs of pharmacological interventions for TD and identify influencing factors. METHODS: A systematic search of the Embase, Medline, Cochrane Central Register of Controlled Trials, and PsycINFO databases was conducted. Eligible studies were RCTs that compared active pharmacological agents with placebos. Placebo response was defined as the change from baseline in TD symptom severity in the placebo group, and nocebo response as the proportion experiencing adverse events (AEs) in this group. Subgroup analysis and meta-regression were performed to explore modifying factors. RESULTS: Twenty-four trials involving 2222 participants were included in this study. A substantial placebo response in TD symptom severity was identified, with a pooled effect size of -0.79 (95% confidence interval [CI] -0.99 to -0.59; I2 = 67%). Forty-four percent (95% CI 27% to 63%; I2 = 92%) of patients experienced AEs while taking inert pills. Sample size, study design, and randomization ratio were correlated with changes in placebo and nocebo responses. CONCLUSION: There were considerable placebo and nocebo responses in TD clinical trials. These results are of great relevance for the design of future trials and for clinical practice in TD. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration ID CRD42023388397. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Clinical and genetic characterization of a Chinese family with pontocerebellar hypoplasia type 7.

We report compound heterozygous variants in TOE1 in siblings of Chinese origin who presented with dyskinesia and intellectual disabilities. Our report provides further information regarding the etiology and pathogenesis of pontocerebellar hypoplasia type 7 syndrome (PCH7). Clinical manifestations were obtained, and genomic DNA was collected from family members. Whole-exome and Sanger sequencing were performed to identify associated genetic variants. Bioinformatics analysis was conducted to identify and characterize the pathogenicity of the heterozygous variants. Following long-term rehabilitation, both siblings showed minimal improvement, and their condition tended to progress. Whole-exome sequencing revealed two unreported heterozygous variants, NM_025077: c.C553T (p.R185W) and NM_025077: c.G562T (p.V188L), in the TOE1 gene mapped to 1p34.1. Sanger sequencing confirmed that the two variants in the proband and her brother were inherited from their parents. The NM_025077: c.C553T (p.R185W) variant was inherited from the father, and the NM_025077: c.G562T (p.V188L) variant was inherited from the mother. Although the two variants in the TOE1 gene have not been reported previously, they were associated with PCH7 based on integrated analysis. Thus, our report contributes to our knowledge regarding the etiology and phenotype of PCH 7.

Coralliovum pocilloporae gen. nov., sp. nov. and Sanyastnella coralliicola gen. nov., sp. nov. isolated from coral tissue: proposal of two new families, Coralliovaceae fam. nov. and Sanyastnellaceae fam. nov.

A genome-based polyphasic approach was used to determine the taxonomic status of two novel bacterial strains, SCSIO 12594T and SCSIO 12813T, isolated from tissues of a coral. Both strains were Gram-stain-negative and facultatively anaerobic. The genome sizes of strains SCSIO 12594T and SCSIO 12813T were 3.9 Mb and 4.1 Mb, respectively, and they possessed DNA G+C contents of 55.1 and 46.2 mol%, respectively . Both strains were found to be catalase- and oxidase-positive, while SCSIO 12594T also could hydrolyse starch. SCSIO 12594T was observed to grow at between 20 and 37 °C (optimally at 25 °C) and at a pH range from 6 to 7 and in the presence of 3-7 % (w/v) NaCl. The growth of SCSIO 12813T required seawater and occurred at 20-30 °C (optimum, 25 °C), pH 5-8 (optimum, pH 6-7) and in the presence of 3-3.7 % (w/v) NaCl. The results of 16S rRNA gene-based phylogenetic analysis indicated that SCSIO 12594T shared 92.97 % or less sequence similarity with its closest relatives Rhodobium gokarnense JA173T and other members of the order Hyphomicrobiales. The results of 16S rRNA sequences-based phylogenetic analysis of SCSIO 12813T indicated that Croceimicrobium hydrocarbonivorans A20-9T (89.34 %) was the most closely related species. SCSIO 12594T and SCSIO 12813T can be readily separated from their closest relatives, as indicated by the results of phylogenomic analysis, low average nucleotide indexes, average amino acid identity, digital DNA-DNA hybridisation (dDDH) similarities and associated phenotypic and chemical data. Consequently, the two coral isolates are considered to represent two novel genera and species for which the names Coralliovum pocilloporae gen. nov., sp. nov. and Sanyastnella coralliicola gen. nov., sp. nov. are proposed, the type strains are SCSIO 12594T (= JCM 35320T = GDMCC 1.3060T) and SCSIO 12813T (= JCM 35373T = GDMCC 1.3063T), respectively. In addition, two novel families, Coralliovaceae fam. nov. and Sanyastnellaceae fam. nov are proposed to accommodate Coralliovum pocilloporae gen. nov., sp. nov. and Sanyastnella coralliicola gen. nov., sp. nov., respectively.

Constructing a Z-Scheme Co3O4/BiOBr Heterojunction to Enhance Photocatalytic Peroxydisulfate Oxidation of High-Concentration Rhodamine B: Mechanism, Degradation Pathways, and Toxicological Evaluations.

Photocatalytic coupling technologies have emerged as popular strategies to increase the treatment efficiency of dye-containing wastewater. Herein, the Z-scheme Co3O4/BiOBr heterojunction (Z-CBH) was constructed and developed as a photocatalytic peroxydisulfate (PDS) activator for the degradation of high-concentration Rhodamine B (RhB). Multiple testing techniques were employed to confirm the formation of Z-CBHs. When 0.1 g·L-1 of Z-CBH20 and 1.0 mmol·L-1 of PDS were added simultaneously under simulated sunlight irradiation, the RhB degradation efficiency could approach 91.3%. Its reaction rate constant (0.01231 min-1) was much beyond the sum of those in the Z-CBH20/light system (0.00436 min-1) and the PDS/light system (0.0062 min-1). h+, •OH, •O2-, SO4•-, and 1O2 were detected as the dominant reactive species for RhB degradation. The potential mechanism of photocatalytic PDS oxidation was proposed. The possible intermediates were determined by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry assisted with density functional theory and Fukui theory. The possible degradation pathways of RhB degradation were put forward. The toxicological properties of RhB and its intermediates were evaluated by quantitative structure-activity relationship prediction. This work will not only provide a reference for developing photocatalytic persulfate activators but also gain an insight into the degradation pathways of RhB and the toxicity of its intermediates.

Elucidating the Mechanism on the Transition-Metal Ion-Synergetic-Catalyzed Oxidation of SO2 with Implications for Sulfate Formation in Beijing Haze.

Currently, atmospheric sulfate aerosols cannot be predicted reliably by numerical models because the pathways and kinetics of sulfate formation are unclear. Here, we systematically investigated the synergetic catalyzing role of transition-metal ions (TMIs, Fe3+/Mn2+) in the oxidation of SO2 by O2 on aerosols using chamber experiments. Our results showed that the synergetic effect of TMIs is critically dependent on aerosol pH due to the solubility of Fe(III) species sensitive to the aqueous phase acidity, which is effective only under pH < 3 conditions. The sulfate formation rate on aerosols is 2 orders of magnitude larger than that in bulk solution and increases significantly on smaller aerosols, suggesting that such a synergetic-catalyzed oxidation occurs on the aerosol surface. The kinetic reaction rate can be described as R = k*[H+]-2.95[Mn(II)][Fe(III)][S(IV)] (pH ≤ 3.0). We found that TMI-synergetic-catalyzed oxidation is the dominant pathway of sulfate formation in Beijing when haze particles are very acidic, while heterogeneous oxidation of SO2 by NO2 is the most important pathway when haze particles are weakly acidic. Our work for the first time clarified the role and kinetics of TMI-synergetic-catalyzed oxidation of SO2 by O2 in haze periods, which can be parameterized into models for future studies of sulfate formation.

Arsenic Reduces Methane Emissions from Paddy Soils: Insights from Continental Investigation and Laboratory Incubations.

Arsenic (As) contamination and methane (CH4) emissions co-occur in rice paddies. However, how As impacts CH4 production, oxidation, and emission dynamics is unknown. Here, we investigated the abundances and activities of CH4-cycling microbes from 132 paddy soils with different As concentrations across continental China using metagenomics and the reverse transcription polymerase chain reaction. Our results revealed that As was a crucial factor affecting the abundance and distribution patterns of the mcrA gene, which is responsible for CH4 production and anaerobic CH4 oxidation. Laboratory incubation experiments showed that adding 30 mg kg-1 arsenate increased 13CO2 production by 10-fold, ultimately decreasing CH4 emissions by 68.5%. The inhibition of CH4 emissions by As was induced through three aspects: (1) the toxicity of As decreased the abundance and activity of the methanogens; (2) the adaptability and response of methanotrophs to As is beneficial for CH4 oxidation under As stress; and (3) the more robust arsenate reduction would anaerobically consume more CH4 in paddies. Additionally, significant positive correlations were observed between arsC and pmoA gene abundance in both the observational study and incubation experiment. These findings enhance our understanding of the mechanisms underlying the interactions between As and CH4 cycling in soils.

Long-Term Efficacy Analysis of Surgical Resection of 70 Primary Right Heart Tumors.

INTRODUCTION: The aim of the study was to investigate the clinical characteristics, surgical treatment, and long-term efficacy of primary right heart tumors. METHODS: This study is retrospective analysis of the clinical data of 70 patients with primary right heart tumors admitted to our department between 1980 and 2022 (observation group) and 70 patients with left heart tumors during the same period (control group). The surgical treatment was performed under cardiopulmonary bypass after differential diagnosis by echocardiography, cardiac CTA, and PET-CT before the surgery. The perioperative characteristics, recurrence rate, and long-term survival rates of right heart tumor versus left heart tumor were compared. RESULTS: The most common pathological types of right heart tumors were myxoma (60%), lipoma (8.57%), and papillary elastofibroma (7.14%). During the perioperative period, there were 1 case of systemic embolism in the observation group, compared with 6 in the control group (p = 0.026), 13 cases of malignant tumor in the observation group versus 1 in the control group (p = 0.01). During the follow-up period, there were 15 cases of tumor recurrence and 17 cases of death in the observation group versus 4 (p = 0.002) and 7 in the control group (p = 0.006), comparatively. CONCLUSION: Compared with left heart tumors, primary right heart tumors had a higher incidence of malignant tumors and a lower risk of systemic embolism during perioperative period. During the follow-up period, primary right heart tumors had a higher rate of tumor recurrence and a lower long-term survival rate.

Bacteria undergo significant shifts while archaea maintain stability in Pocillopora damicornis under sustained heat stress.

Global warming reportedly poses a critical risk to coral reef ecosystems. Bacteria and archaea are crucial components of the coral holobiont. The response of archaea associated with warming is less well understood than that of the bacterial community in corals. Also, there have been few studies on the dynamics of the microbial community in the coral holobiont under long-term heat stress. In order to track the dynamic alternations in the microbial communities within the heat-stressed coral holobiont, three-week heat-stress monitoring was carried out on the coral Pocillopora damicornis. The findings demonstrate that the corals were stressed at 32 °C, and showed a gradual decrease in Symbiodiniaceae density with increasing duration of heat stress. The archaeal community in the coral holobiont remained relatively unaltered by the increasing temperature, whereas the bacterial community was considerably altered. Sustained heat stress exacerbated the dissimilarities among parallel samples of the bacterial community, confirming the Anna Karenina Principle in animal microbiomes. Heat stress leads to more complex and unstable microbial networks, characterized by an increased average degree and decreased modularity, respectively. With the extension of heat stress duration, the relative abundances of the gene (nifH) and genus (Tistlia) associated with nitrogen fixation increased in coral samples, as well as the potential pathogenic bacteria (Flavobacteriales) and opportunistic bacteria (Bacteroides). Hence, our findings suggest that coral hosts might recruit nitrogen-fixing bacteria during the initial stages of suffering heat stress. An environment that is conducive to the colonization and development of opportunistic and pathogenic bacteria when the coral host becomes more susceptible as heat stress duration increases.

Recent progress of non-linear topological structure polymers: synthesis, and gene delivery.

Currently, many types of non-linear topological structure polymers, such as brush-shaped, star, branched and dendritic structures, have captured much attention in the field of gene delivery and nanomedicine. Compared with linear polymers, non-linear topological structural polymers offer many advantages, including multiple terminal groups, broad and complicated spatial architecture and multi-functionality sites to enhance gene delivery efficiency and targeting capabilities. Nevertheless, the complexity of their synthesis process severely hampers the development and applications of nonlinear topological polymers. This review aims to highlight various synthetic approaches of non-linear topological architecture polymers, including reversible-deactivation radical polymerization (RDRP) including atom-transfer radical polymerization (ATRP), nitroxide-mediated polymerization (NMP), reversible addition-fragmentation chain transfer (RAFT) polymerization, click chemistry reactions and Michael addition, and thoroughly discuss their advantages and disadvantages, as well as analyze their further application potential. Finally, we comprehensively discuss and summarize different non-linear topological structure polymers for genetic materials delivering performance both in vitro and in vivo, which indicated that topological effects and nonlinear topologies play a crucial role in enhancing the transfection performance of polymeric vectors. This review offered a promising guideline for the design and development of novel nonlinear polymers and facilitated the development of a new generation of polymer-based gene vectors.