Neoadjuvant PARPi or chemotherapy in ovarian cancer informs targeting effector Treg cells for homologous-recombination-deficient tumors.

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD and neoadjuvant therapies, co-occurring with other tumor-reactive T cells, particularly terminally exhausted CD8+ T cells (Tex). TME-wide interferon signaling correlates with cancer cells upregulating MHC class II and co-inhibitory ligands, potentially driving Treg and Tex fates. Depleting eTregs in HRD mouse models, with or without PARP inhibition, significantly suppresses tumor growth without observable toxicities, underscoring the potential of eTreg-focused therapeutics for HGSOC and other HRD-related tumors.

Integrating multiregulatory analysis reveals the negative regulatory function of miR482a in the response of poplar to canker pathogen infection.

Canker disease caused by the bacterium Lonsdalea populi is one of the most destructive diseases affecting poplar stems. However, the detailed stress response mechanisms of poplar have not been widely characterized. To explore the diverse regulatory RNA landscape and the function of key regulators in poplar subjected to L. populi stress, we integrated time-course experiment with mock-inoculation (CK) and inoculation (IN) with L. populi at the first, third, and sixth day (IN1, IN3, IN6) on Populus × euramericana cv. '74/76' (107), small RNA-seq, whole transcriptome-wide analysis, degradome analysis and transgenic experiments. A total of 98 differentially expressed (DE) miRNA, 17 974 DEmRNA, and 807 DElncRNA were identified in poplar infected by L. populi, presenting dynamic changes over the infection course. Regulatory networks among RNAs were further constructed. Notably, a network centered on ptc-miR482a in CK-vs-IN3 contained most DEGs. We show that miR482a and miR1448 are located in one transcript as a polycistron. Overexpression of pre-miR482a-miR1448 (OX482-1448) and pre-miR482a (OX482) increased poplar susceptibility to canker pathogen with reduced accumulation of reactive oxygen species, while the suppression of miR482a (STTM482) conferred poplar disease resistance. PHA7 was validated as the target of miR482a with degradome sequencing and tobacco transient co-transformation, its expression being downregulated in OX482-1448 and OX482 lines. Additionally, a series of phasiRNAs were triggered by miR482a targeting PHA7, forming regulatory cascades with more RLP, NBS-LRR, and PK genes, further verifying the defense function of miR482a. These findings provide insights for understanding the roles of ncRNAs and regulatory networks involved in poplar immunity.

Dual electronic effects achieving a high-performance Ni(II) pincer catalyst for CO2 photoreduction in a noble-metal-free system.

A carbazolide-bis(NHC) NiII catalyst (1; NHC, N-heterocyclic carbene) for selective CO2 photoreduction was designed herein by a one-stone-two-birds strategy. The extended π-conjugation and the strong σ/π electron-donation characteristics (two birds) of the carbazolide fragment (one stone) lead to significantly enhanced activity for photoreduction of CO2 to CO. The turnover number (TON) and turnover frequency (TOF) of 1 were ninefold and eightfold higher than those of the reported pyridinol-bis(NHC) NiII complex at the same catalyst concentration using an identical Ir photosensitizer, respectively, with a selectivity of ∼100%. More importantly, an organic dye was applied to displace the Ir photosensitizer to develop a noble-metal-free photocatalytic system, which maintained excellent performance and obtained an outstanding quantum yield of 11.2%. Detailed investigations combining experimental and computational studies revealed the catalytic mechanism, which highlights the potential of the one-stone-two-birds effect.

LTF ameliorates cartilage endplate degeneration by suppressing calcification, senescence and matrix degradation through the JAK2/STAT3 pathway.

Intervertebral disc degeneration (IDD)-induced cervical and lumbar herniations are debilitating diseases. The function of intervertebral disc (IVD) mainly depends on the cartilage endplate (CEP), which provides support and waste removal. Therefore, IDD stems from the degeneration of CEP. Our study shows that the expression of lactotransferrin (LTF), an iron-binding protein, is significantly decreased in degenerated human and rat CEP tissues. In addition, we found that LTF knockdown promoted calcification, senescence, and extracellular matrix (ECM) degradation in human endplate chondrocytes. Furthermore, the in vivo experiment results confirmed that the JAK2/STAT3 pathway inhibitor AG490 significantly reversed these effects. In addition to investigating the role and mechanism of LTF in CEP degeneration, this study provides a theoretical basis and experimental evidence to improve IDD treatment.

Basic helix-loop-helix (bHLH) gene family in rye (Secale cereale L.): genome-wide identification, phylogeny, evolutionary expansion and expression analyses.

BACKGROUND: Rye (Secale cereale), one of the drought and cold-tolerant crops, is an important component of the Triticae Dumortier family of Gramineae plants. Basic helix-loop-helix (bHLH), an important family of transcription factors, has played pivotal roles in regulating numerous intriguing biological processes in plant development and abiotic stress responses. However, no systemic analysis of the bHLH transcription factor family has yet been reported in rye. RESULTS: In this study, 220 bHLH genes in S. cereale (ScbHLHs) were identified and named based on the chromosomal location. The evolutionary relationships, classifications, gene structures, motif compositions, chromosome localization, and gene replication events in these ScbHLH genes are systematically analyzed. These 220 ScbHLH members are divided into 21 subfamilies and one unclassified gene. Throughout evolution, the subfamilies 5, 9, and 18 may have experienced stronger expansion. The segmental duplications may have contributed significantly to the expansion of the bHLH family. To systematically analyze the evolutionary relationships of the bHLH family in different plants, we constructed six comparative genomic maps of homologous genes between rye and different representative monocotyledonous and dicotyledonous plants. Finally, the gene expression response characteristics of 22 ScbHLH genes in various biological processes and stress responses were analyzed. Some candidate genes, such as ScbHLH11, ScbHLH48, and ScbHLH172, related to tissue developments and environmental stresses were screened. CONCLUSIONS: The results indicate that these ScbHLH genes exhibit characteristic expression in different tissues, grain development stages, and stress treatments. These findings provided a basis for a comprehensive understanding of the bHLH family in rye.

Aqueous Zinc-Iodine Pouch Cells with Long Cycling Life and Low Self-Discharge.

Aqueous zinc batteries are practically promising for large-scale energy storage because of cost-effectiveness and safety. However, application is limited because of an absence of economical electrolytes to stabilize both the cathode and anode. Here, we report a facile method for advanced zinc-iodine batteries via addition of a trace imidazolium-based additive to a cost-effective zinc sulfate electrolyte, which bonds with polyiodides to boost anti-self-discharge performance and cycling stability. Additive aggregation at the cathode improves the rate capacity by boosting the I2 conversion kinetics. Also, the introduced additive enhances the reversibility of the zinc anode by adjusting Zn2+ deposition. The zinc-iodine pouch cell, therefore, exhibits industrial-level performance evidenced by a ∼99.98% Coulombic efficiency under ca. 0.4C, a significantly low self-discharge rate with 11.7% capacity loss per month, a long lifespan with 88.3% of initial capacity after 5000 cycles at a 68.3% zinc depth-of-discharge, and fast-charging of ca. 6.7C at a high active-mass loading >15 mg cm-2. Highly significant is that this self-discharge surpasses commercial nickel-metal hydride batteries and is comparable with commercial lead-acid batteries, together with the fact that the lifespan is over 10 times greater than reported works, and the fast-charging performance is better than commercial lithium-ion batteries.

PNA-Functionalized, Silica Nanowires-Filled Glass Microtube for Ultrasensitive and Label-Free Detection of miRNA-21.

MicroRNAs (miRNAs) are endogenous and noncoding single-stranded RNA molecules with a length of approximately 18-25 nucleotides, which play an undeniable role in early cancer screening. Therefore, it is very important to develop an ultrasensitive and highly specific method for detecting miRNAs. Here, we present a bottom-up assembly approach for modifying glass microtubes with silica nanowires (SiNWs) and develop a label-free sensing platform for miRNA-21 detection. The three-dimensional (3D) networks formed by SiNWs make them abundant and highly accessible sites for binding with peptide nucleic acid (PNA). As a receptor, PNA has no phosphate groups and exhibits an overall electrically neutral state, resulting in a relatively small repulsion between PNA and RNA, which can improve the hybridization efficiency. The SiNWs-filled glass microtube (SiNWs@GMT) sensor enables ultrasensitive, label-free detection of miRNA-21 with a detection limit as low as 1 aM at a detection range of 1 aM-100 nM. Noteworthy, the sensor can still detect miRNA-21 in the range of 102-108 fM in complex solutions containing 1000-fold homologous interference of miRNAs. The high anti-interference performance of the sensor enables it to specifically recognize target miRNA-21 in the presence of other miRNAs and distinguish 1-, 3-mismatch nucleotide sequences. Significantly, the sensor platform is able to detect miRNA-21 in the lysate of breast cancer cell lines (e.g., MCF-7 cells and MDA-MB-231 cells), indicating that it has good potential in the screening of early breast cancers.

Ion-Selective Micropipette Sensor for In Vivo Monitoring of Sodium Ion with Crown Ether-Encapsulated Metal-Organic Framework Subnanopores.

In vivo sensing of the dynamics of ions with high selectivity is essential for gaining molecular insights into numerous physiological and pathological processes. In this work, we report an ion-selective micropipette sensor (ISMS) through the integration of functional crown ether-encapsulated metal-organic frameworks (MOFs) synthesized in situ within the micropipette tip. The ISMS features distinctive sodium ion (Na+) conduction and high selectivity toward Na+ sensing. The selectivity is attributed to the synergistic effects of subnanoconfined space and the specific coordination of 18-crown-6 toward potassium ions (K+), which largely increase the steric hindrance and transport resistance for K+ to pass through the ISMS. Furthermore, the ISMS exhibits high stability and sensitivity, facilitating real-time monitoring of Na+ dynamics in the living rat brain during spreading of the depression events process. In light of the diversity of crown ethers and MOFs, we believe this study paves the way for a nanofluidic platform for in vivo sensing and neuromorphic electrochemical sensing.

Structural Engineering of Co-Metal-Organic Frameworks via Ce Incorporation for Improved Oxygen Evolution.

The rational design of metal-organic framework (MOF)-based electrocatalysts plays a key role in achieving high-efficiency oxygen evolution reaction (OER). Herein, a synergetic morphology and electronic structure engineering strategy are proposed to design a Co-MOF nanoflower grown on carbon paper via rare-earth cerium doping (CoCe-MOF/CP). Compared with Co-MOF/CP, the developed CoCe-MOF/CP exhibited superior OER performance with a low overpotential of 267 mV at 10 mA cm-2 and outstanding long-term stability over 100 h. Theoretical calculations show that the unique 4f valence electron structure of Ce induced charge redistribution of the Co-MOF surface through the strong Co 3d-O 2p-Ce 4f orbital electronic coupling below the Fermi level. Ce-doped plays a key role in the engineering of the electronic states of the Co sites to endow them with the optimal free energy landscape for enhanced OER catalytic activity. This work provides new insights into comprehending the RE-enhanced mechanism of electrocatalysis and provides an effective strategy for the design of MOF-based electrocatalysts.

Toxin genotypes, antibiotic resistance and their correlations in Clostridioides difficile isolated from hospitals in Xi'an, China.

BACKGROUND: Clostridioides difficile is the main pathogen of antimicrobial-associated diarrhoea and health care facility-associated infectious diarrhoea. This study aimed to investigate the prevalence, toxin genotypes, and antibiotic resistance of C. difficile among hospitalized patients in Xi'an, China. RESULTS: We isolated and cultured 156 strains of C. difficile, representing 12.67% of the 1231 inpatient stool samples collected. Among the isolates, tcdA + B + strains were predominant, accounting for 78.2% (122/156), followed by 27 tcdA-B + strains (27/156, 17.3%) and 6 binary toxin gene-positive strains. The positive rates of three regulatory genes, tcdC, tcdR, and tcdE, were 89.1% (139/156), 96.8% (151/156), and 100%, respectively. All isolates were sensitive to metronidazole, and the resistance rates to clindamycin and cephalosporins were also high. Six strains were found to be resistant to vancomycin. CONCLUSION: Currently, the prevalence rate of C. difficile infection (CDI) in Xi'an is 12.67% (156/1231), with the major toxin genotype of the isolates being tcdA + tcdB + cdtA-/B-. Metronidazole and vancomycin were still effective drugs for the treatment of CDI, but we should pay attention to antibiotic management and epidemiological surveillance of CDI.

Impact of third-order dispersion on the dynamics of dissipative solitons in an ultrafast fiber laser.

Dissipative solitons (DSs), due to the complex interplay among dispersion, nonlinear, gain and loss, illustrate abundant nonlinear dynamics behaviors. Especially, dispersion plays an important role in the research of DS dynamics in ultrafast fiber lasers. Previous studies have mainly focused on the effect of even-order dispersion, i.e., group velocity dispersion (GVD) and fourth-order dispersion. In fact, odd-order dispersions, such as third-order dispersion (TOD), also significantly influences the dynamics of DSs. However, due to the lack of dispersion engineering tools, few experimental researches in this domain have been reported. In this work, by employing a pulse shaper in ultrafast fiber laser, an in-depth exploration of the DS dynamics influenced by TOD was conducted. With the increase of TOD value, the stable single DS undergoes a splitting into two solitons and then enters explosion state, and ultimately evolves into a chaotic state. The laser operation state is correlated to dispersion profile, which could be controlled by TOD. Here, the positive dispersion at long-wavelength side will be gradually shifted to negative dispersion by increasing the TOD, where soliton effect will drive the transitions. These findings offer valuable insights into the nonlinear dynamics of ultrafast lasers and may also foster applications involving higher-order dispersion.

CCDC25 suppresses clear cell renal cell carcinoma progression by LATS1/YAP-mediated regulation of the hippo pathway.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent renal cancers, and the molecular mechanisms underlying its progression are still not fully understood. The expression of CCDC25, a notably underexpressed gene in many tumors, has been understudied in ccRCC. This research aims to explore the role of CCDC25 in ccRCC's clinical outcomes and uncover the molecular pathways influenced by it. METHODS: A multi-tiered approach was adopted involving bioinformatic analysis, tissue sample evaluation, in vitro and in vivo experiments. CCDC25 expression levels in tumor vs. normal tissues were quantified using Western blot and immunofluorescence studies. Cell proliferation and migration were analyzed using CCK8, EDU, Transwell assays, and wound healing assays. RNA sequencing was performed to elucidate the molecular pathways affected, followed by detailed protein-protein interaction studies and mouse xenograft models. RESULTS: CCDC25 was predominantly underexpressed in ccRCC tumors and associated with advanced clinical stages and poor prognosis. Overexpression of CCDC25 in renal cancer cell lines resulted in reduced proliferation and migration. RNA sequencing revealed significant alterations in the Hippo pathway. Overexpression of CCDC25 inhibited the expression of downstream Hippo pathway proteins ITGA3 and CCND1 and promoted YAP phosphorylation. Mechanistic studies showed that CCDC25 interacts with YAP and influences YAP phosphorylation through LATS1. In vivo, CCDC25 overexpression inhibited tumor growth and promoted apoptosis. CONCLUSION: CCDC25 acts as a potential tumor suppressor in ccRCC by inhibiting cell proliferation and migration, potentially through regulating the Hippo signaling pathway. These findings highlight the potential of CCDC25 as a therapeutic target in ccRCC treatment.

Birthweight influences liver structure, function and disease risk: Evidence of a causal association.

AIM: Low birthweight is an issue during pregnancy associated with an increased risk of developing liver disease later in life. Previous Mendelian randomisation (MR) studies which explored this issue have not isolated the direct impact of the foetus on birthweight. In the present study, MR was used to assess whether direct foetal effects on birthweight were causally associated with liver structure, function and disease risk independent of intrauterine effects. MATERIALS AND METHODS: We extracted single nucleotide polymorphisms (SNPs) from genome-wide association studies (GWAS) about direct foetal-affected birthweight (321 223 cases) to conduct univariable and multivariable MR analyses to explore the relationships between birthweight and 4 liver structure measures, 9 liver function measures and 18 liver diseases. A two-step MR analysis was used to further assess and quantify the mediating effects of the mediators. RESULTS: When isolating direct foetal effects, genetically predicted lower birthweight was associated with a higher risk of non-alcoholic fatty liver disease (NAFLD) (odds ratios [OR], 95% confidence interval [CI]: 1.61, 1.29-2.02, p < 0.001), higher magnetic resonance imaging [MRI] proton density fat fraction (PDFF) and higher serum gamma glutamyltransferase (GGT). Two-step MR identified two candidate mediators that partially mediate the direct foetal effect of lower birthweight on NAFLD, including fasting insulin (proportion mediated: 22.29%) and triglycerides (6.50%). CONCLUSIONS: Our MR analysis reveals a direct causal association between lower birthweight and liver MRI PDFF, as well as the development of NAFLD, which persisted even after accounting for the potential influence of maternal factors. In addition, we identified fasting insulin and triglycerides as mediators linking birthweight and hepatic outcomes, providing insights for early clinical interventions.

Development of Axially Chiral Pyridylidene Amine Ligands and their Application in Pd-Catalyzed Enantioselective Allylic Substitution.

A series of novel axially chiral pyridylidene amine (PYE) ligands has been developed, and their catalytic capability has been demonstrated in various highly efficient and enantioselective Pd-catalyzed asymmetric allylic substitutions. A density-functional theory (DFT) study explains the preferential enantiocontrol in the key transition states of the axially chiral PYE ligand-promoted Pd-catalyzed allylic alkylation.

Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study.

BACKGROUND: Little is known regarding the leading risk factors for dementia/Alzheimer's disease (AD) in individuals with and without APOE4. The identification of key risk factors for dementia/Alzheimer's disease (AD) in individuals with and without the APOE4 gene is of significant importance in global health. METHODS: Our analysis included 110,354 APOE4 carriers and 220,708 age- and sex-matched controls aged 40-73 years at baseline (between 2006-2010) from UK Biobank. Incident dementia was ascertained using hospital inpatient, or death records until January 2021. Individuals of non-European ancestry were excluded. Furthermore, individuals without medical record linkage were excluded from the analysis. Moderation analysis was tested for 134 individual factors. RESULTS: During a median follow-up of 11.9 years, 4,764 cases of incident all-cause dementia and 2065 incident AD cases were documented. Hazard ratios (95% CIs) for all-cause dementia and AD associated with APOE4 were 2.70(2.55-2.85) and 3.72(3.40-4.07), respectively. In APOE4 carriers, the leading risk factors for all-cause dementia included low self-rated overall health, low household income, high multimorbidity risk score, long-term illness, high neutrophil percentage, and high nitrogen dioxide air pollution. In non-APOE4 carriers, the leading risk factors included high multimorbidity risk score, low overall self-rated health, low household income, long-term illness, high microalbumin in urine, high neutrophil count, and low greenspace percentage. Population attributable risk for these individual risk factors combined was 65.1%, and 85.8% in APOE4 and non-APOE4 carriers, respectively. For 20 risk factors including multimorbidity risk score, unhealthy lifestyle habits, and particulate matter air pollutants, their associations with incident dementia were stronger in non-APOE4 carriers. For only 2 risk factors (mother's history of dementia, low C-reactive protein), their associations with incident all-cause dementia were stronger in APOE4 carriers. CONCLUSIONS: Our findings provide evidence for personalized preventative approaches to dementia/AD in APOE4 and non-APOE4 carriers. A mother's history of dementia and low levels of C-reactive protein were more important risk factors of dementia in APOE4 carriers whereas leading risk factors including unhealthy lifestyle habits, multimorbidity risk score, inflammation and immune-related markers were more predictive of dementia in non-APOE4 carriers.

Predictive Factors for Residual Low Back Pain Following Percutaneous Endoscopic Lumbar Discectomy in Patients with Lumbar Disc Herniation.

BACKGROUND Percutaneous endoscopic lumbar discectomy (PELD) is a mature and popular surgery for treatment of lumbar disc herniation (LDH). The main objective of our study was to identify risk factors for residual low back pain after PELD and to improve postoperative management. MATERIAL AND METHODS We retrospectively analyzed the clinical and imaging data of 251 patients who underwent PELD for LDH. We defined residual LBP as visual analog scale (VAS) score for LBP ≥3 at 2 years postoperatively, and severe LBP was defined as VAS for LBP ≥7.5. The clinical and imaging data were analyzed by comparing patients with VAS scores ≥3 and <3, and univariate analysis and multivariable logistic regression analysis were applied to predict the risk factors for residual LBP. RESULTS There were 56 (22.3%) patients with LBP VAS ≥3 at 2 years postoperatively. Multivariable logistic regression analysis demonstrated that severe baseline VAS for LBP (P<0.001), MCs type I (P=0.006), and severe fatty infiltration of the paravertebral muscles (P<0.001) were independent risk factors for residual LBP after PELD. CONCLUSIONS In patients with LDH, MCs type I, severe baseline LBP, and fatty infiltration of the paravertebral muscles were predictive factors for residual LBP after PELD. Our study suggests that spine surgeons should pay more attention to these imaging parameters, which may be a helpful indicator for the choice of surgical modality.

Enterococcus faecium inhibits NF-κB/NLRP3/Caspase-1 signaling pathway to antagonize enterotoxigenic Escherichia coli-mediated inflammatory response.

Enterotoxigenic Escherichia coli (ETEC) can cause intestinal inflammation and diarrhea in yaks, which has a negative impact on their economic value. In recent years, probiotics have gained increasing attention as a pure, natural, nontoxic, harmless, and residue-free additive. However, the underlying mechanisms by which probiotics safeguard against ETEC are not completely elucidated. This study aimed to investigate the protective effect of Enterococcus faecium (E. faecium) against ETEC infection in mice through oral gavage. Morphological changes were examined through light microscopy. The expressions of inflammatory cytokines (IL-1ß, IL-6, TNF-α, IL-10, NF-κB, and NLRP3), tight junction protein (ZO-1, Claudin-1), and pyroptosis (Caspase-1, Caspase-4, and gasdermin D (GSDMD)) were detected using immunohistochemistry and quantitative real-time PCR. The results indicate that ETEC infection triggers the activation of inflammation-related pathways (NF-κB) and NLRP3 inflammasome, leading to the expression of a large number of inflammatory cytokines. Additionally, the activation of NLRP3 leads to the release of GSDMD activation through Caspase-1, ultimately resulting in inflammatory injury and pyroptosis. Feeding mice E. faecium early resulted in an increase in the expression of tight junction protein, a reduction in inflammatory cytokines, and alleviation of inflammatory injury and pyroptosis in intestinal tissues. Our research indicates that E. faecium has the ability to antagonize ETEC and provide protection to the gastrointestinal mucosa in mice.

Neurosurgical clipping versus endovascular coiling for patients with ruptured anterior circulation aneurysms: A systematic review and meta-analysis.

To compare the safety and efficacy of clipping and coiling in patients with ruptured anterior circulation aneurysms. A systematic search of four databases (PubMed, Web of Science, Cochrane Library, and Embase) was conducted to identify comparative articles on endovascular coiling and surgical clipping in patients with ruptured anterior circulation aneurysms. Meta-analyses were conducted using random-effects models. Nineteen studies, including 1983 patients, were included. The meta-analysis showed that neurosurgical clipping was associated with a lower incidence of retreatment (OR:0.28, 95% CI (0.11, 0.70), P = 0.006) than endovascular coiling, which seemed to be a result of incomplete occlusion (OR:0.22, 95% CI (0.11, 0.45), P < 0.001). Neurosurgical clipping was associated with lower mortality (OR:0.45, 95% CI (0.25, 0.82), P = 0.009) at short-term follow-up than endovascular coiling. However, neurosurgical clipping showed a higher incidence of ischemic infarction (OR:2.28, 95% CI (1.44, 3.63), P < 0.001) and a longer length of stay (LOS) (WMD:6.12, 95% CI (4.19, 8.04), P < 0.001) after surgery than endovascular coiling. Furthermore, the pooled results showed no statistically significant differences between the two groups regarding poor outcome, long-term mortality, rebleeding, vasospasm, and hydrocephalus. Evidence from this systematic review illustrates that neurosurgical clipping may be superior to endovascular coiling for ruptured anterior circulation aneurysms. Large-scale RCTs should be conducted to verify these outcomes and provide results according to patient status.

Various effects of feeding level on ammonia tolerance in Carassius auratus under different ammonia exposure stress and the underlying mechanisms.

Elevated ammonia levels in aquaculture systems could reduce fish growth and survival rates and produce a range of physiological problems. Ammonia toxicity in aquatic environments was regulated by various factors. Feeding was usually reported to help in the detoxification of fish, thereby increasing their capacity to tolerate ammonia nitrogen. However, the impact of different feeding amounts on fish in relation to ammonia exposure stress remains to be determined. To determine how feeding levels affected fish's responses to different ammonia nitrogen concentrations, two acute toxicity experiments were conducted with Carassius auratus gibelio, the major strain of gibel carp in aquaculture systems in China. In Test I, fed Carassius auratus gibelio (3 % body weight) showed a higher survival rate under a specific ammonia exposure stress. 96-h LC50 of NH3-N to 3 %F gibel carp was 1.1 times greater than that for NF (no feeding). In Test II, all fed groups (2 %F and 4 %F) under low and high ammonia stress exhibited improved ammonia detoxification, evidenced by higher liver GSase, GDH, and glutamine concentrations compared with the NF treatment. Muscle glycogen levels in feeding treatments were higher than those in NF, indicating that fed fish have more energy for ammonia detoxification. While compared with low ammonia treatment (2.70 mg L-1 TAN; NH3 0.06 mg L-1), fish exposed to high ammonia levels (26.03 mg L-1 TAN; NH3 0.57 mg L-1) demonstrated a decrease in food consumption, severe histopathological alterations in their liver, gill, and kidney, and decreased GSase, GDH, and glutamine production in the liver and brain. The results partly supported our hypothesis and suggested that increasing feeding enhances gibel carp's tolerance to ammonia nitrogen. The highest detoxification metabolism was observed under low ammonia stress. While excessive ammonia exposure could inhibit feeding and damage the detoxification organs of fish, and thus reduce the detoxification metabolism of gibel carp.

Benthic primary production decreases internal phosphorus loading from lake sediments under light supplement.

In aquatic ecosystems, light penetrating the sediment surface in shallow lakes may regulate the internal phosphorus (P) release through benthic primary production, which subsequently affects oxidation, pH levels, and alkaline phosphatase activity in the upper sediment. To study the effects of light exposure on the P dynamics at the sediment-water interface under eutrophic conditions, a two-month mesocosm experiment was conducted in twelve cement tanks (1000 L each). The tanks were equipped with Light-Emitting Diode (LED) lights, and surface sediments collected from eutrophic Lake Nanhu (China) were exposed to four different light intensities (0, 50, 100, 200 µmol m-2 s-1). The results revealed that: 1) Both the total phosphorus concentration and the phosphorus release flux from the sediment were lower in the light treatments (mean value, 0.59-0.71 mg L-1 and 0.00-0.01 mg m-2 d-1, respectively) than in the control treatment (0.77 mg L-1 and 0.01 mg m-2 d-1, respectively), indicating that light supplement could decrease the internal P release. 2) Benthic primary production promoted by light directly absorbed soluble reactive phosphorus and decreased the internal P release. The resulting improved production could also increase dissolved oxygen concentrations at the sediment-water interface, thus indirectly inhibiting internal P release. 3) The relative contributions of direct absorption and indirect inhibition on the internal P release ranged between 23% to 69% and 31% to 77% depending on the light intensity.