Wheel-Running Exercise Alleviates Anxiety-Like Behavior via Down-Regulating S-Nitrosylation of Gephyrin in the Basolateral Amygdala of Male Rats.

Physical exercise has beneficial effect on anxiety disorders, but the underlying molecular mechanism remains largely unknown. Here, it is demonstrated that physical exercise can downregulate the S-nitrosylation of gephyrin (SNO-gephyrin) in the basolateral amygdala (BLA) to exert anxiolytic effects. It is found that the level of SNO-gephyrin is significantly increased in the BLA of high-anxiety rats and a downregulation of SNO-gephyrin at cysteines 212 and 284 produced anxiolytic effect. Mechanistically, inhibition of SNO-gephyrin by either Cys212 or Cys284 mutations increased the surface expression of GABAAR γ2 and the subsequent GABAergic neurotransmission, exerting anxiolytic effect in male rats. On the other side, overexpression of neuronal nitric oxide synthase in the BLA abolished the anxiolytic-like effects of physical exercise. This study reveals a key role of downregulating SNO-gephyrin in the anxiolytic effects of physical exercise, providing a new explanation for protein post-translational modifications in the brain after exercise.

Characteristics analysis of hepatitis B core-related antigen in children with hepatitis B e antigen-positive chronic viral hepatitis B infection.

BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups (P = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB (R2 = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

Melatonin Ameliorates Depressive-Like Behaviors in Ovariectomized Mice by Improving Tryptophan Metabolism via Inhibition of Gut Microbe Alistipes Inops.

Melatonin (N-acetyl-5-methoxytryptamine) is reported to improve mood disorders in perimenopausal women and gut microbiome composition is altered during menopausal period. The possible role of microbiome in the treatment effect of melatonin on menopausal depression remains unknown. Here, it is shown that melatonin treatment reverses the gut microbiota dysbiosis and depressive-like behaviors in ovariectomy (OVX) operated mice. This effect of melatonin is prevented by antibiotic cocktails (ABX) treatment. Transferring microbiota harvested from adolescent female mice to OVX-operated mice is sufficient to ameliorate depressive-like behaviors. Conversely, microbiota transplantation from OVX-operated mice or melatonin-treated OVX-operated mice to naïve recipient mice exhibits similar phenotypes to donors. The colonization of Alistipes Inops, which is abundant in OVX-operated mice, confers the recipient with depressive-like behaviors. Further investigation indicates that the expansion of Alistipes Inops induced by OVX leads to the degradation of intestinal tryptophan, which destroys systemic tryptophan availability. Melatonin supplementation restores systemic tryptophan metabolic disorders by suppressing the growth of Alistipes Inops, which ameliorates depressive-like behaviors. These results highlight the previously unrecognized role of Alistipes Inops in the modulation of OVX-induced behavioral disorders and suggest that the application of melatonin to inhibit Alistipes Inops may serve as a potential strategy for preventing menopausal depressive symptoms.

Comparative Anti-Cancer and Anti-Inflammatory Activities of Essential Oils from the Bark and Flower of Magnolia officinalis Rehd. et Wils.

This study was designed to compare the antioxidant, antitumor and anti-inflammatory effects of essential oils from the bark and flower of Magnolia officinalis Rehd. et Wils. Distillation extraction and steam distillation were used to extract EOs from the bark and flower. The results showed that the contents of EOs of SDE-F and SDE-B were much higher than that of SD-F and SD-B. EOs from the bark were rich in eudesmol (especially α-eudesmol) and exhibited a stronger antioxidant effect than the flower. The anti-tumor effects of SD-B and SD-F on HepG2 and MDA-MB-231 cells were better than that of SDE-B and SDE-F. The inhibitory rates of SD-B and SD-F on MDA-MB-231 cells were 59.21% and 48.27%, exceeding that of positive control 5-fluorouracil (47.04%) at 50 µg/mL. All four EOs exhibited excellent anti-inflammatory activities through the regulation of nitric oxide production and pro-inflammation cytokines in LPS-induced RAW 264.7 cells and they also remarkably suppressed the mRNA expressions of nitric oxide synthase, IL-6 and TNF-α at the concentration higher than that of positive control dexamethasone. These results indicated significant differences in the composition, and anti-inflammatory and anti-tumor activities of EOs extracted by different methods and provided a theoretical basis for their development and utilization.

[Analysis of saliva and intestinal microbial community in children with severe caries based on 16S rDNA high-throughput sequencing technology].

PURPOSE: The characteristics of saliva and intestinal microbial community in children with high caries and no caries were analyzed by 16S rDNA high-throughput sequencing. METHODS: Among 431 children aged 3-5 years old in Zunyi City who were investigated previously by our team, 25 children in the high caries group and the same in the caries-free group were selected for fecal and saliva samples. 16S rDNA high-throughput sequencing was used to analyze the bacterial flora structure of the samples and identify the species with different relative abundance at the species level. SPSS 18.0 software package was used for data analysis. RESULTS: The diversity of intestinal flora in the high caries group was higher than that in the caries-free group, and the difference was statistically significant(P＜0.05). The diversity of salivary flora in the high caries group was more than that in the caries-free group, with no significant difference(P＞0.05). At phylum level,there was no significant difference in intestinal and salivary flora between children with high caries and children without caries. At gene level, Blautia, [Eubacterium] hallii group and [Eubacterium] eligens group in the intestine of caries-free group were significantly higher than those of high caries group(P＜0.05), while Parasutterella and Christensenellaceae R-7 group were significantly lower than those of high caries group(P＜0.05). At gene level, Peptostreptococcus in saliva of caries-free group was significantly higher than that in high caries group(P＜0.05). Dialister, Kingella, Escherichia-Shigella and Treponema in saliva of caries-free group were significantly lower than those in high caries group(P＜0.05). CONCLUSIONS: There are significant differences in species composition of intestinal flora but no in salivary flora between children with high caries and children without caries.

Ultrasound assessment of diaphragmatic dysfunction in non-critically ill patients: relevant indicators and update.

Diaphragm dysfunction (DD) can be classified as mild, resulting in diaphragmatic weakness, or severe, resulting in diaphragmatic paralysis. Various factors such as prolonged mechanical ventilation, surgical trauma, and inflammation can cause diaphragmatic injury, leading to negative outcomes for patients, including extended bed rest and increased risk of pulmonary complications. Therefore, it is crucial to protect and monitor diaphragmatic function. Impaired diaphragmatic function directly impacts ventilation, as the diaphragm is the primary muscle involved in inhalation. Even unilateral DD can cause ventilation abnormalities, which in turn lead to impaired gas exchange, this makes weaning from mechanical ventilation challenging and contributes to a higher incidence of ventilator-induced diaphragm dysfunction and prolonged ICU stays. However, there is insufficient research on DD in non-ICU patients, and DD can occur in all phases of the perioperative period. Furthermore, the current literature lacks standardized ultrasound indicators and diagnostic criteria for assessing diaphragmatic dysfunction. As a result, the full potential of diaphragmatic ultrasound parameters in quickly and accurately assessing diaphragmatic function and guiding diagnostic and therapeutic decisions has not been realized.

Effect of κ-carrageenan on the quality of crayfish surimi gels.

The demand for crayfish surimi products has grown recently due to its high protein content. This study examined the effects of varying κ-carrageenan (CAR) and crayfish surimi (CSM) concentrations on the gelling properties of CAR-CSM composite gel and its intrinsic formation process. Our findings demonstrated that with the increasing concentration of carrageenan, the quality of CAR-CSM exhibited rising trend followed by subsequently fall. Based on the textural qualities, the highest quality CAR-CSM was achieved at 0.3% carrageenan addition. With the exception of chewiness, and the cooking loss of the gel system was 1.62%, whiteness was 82.35%, and the percentage of ß-sheets increased to 57.18%. Further increase in CAR (0.4-0.5%) addition resulted in internal build-up of LCAR-CSM, conversion of intermolecular forces into disulfide bonds and gel breakage. This study exudes timely recommendations for extending the CAR application for the continuous development of crayfish surimi and its derivatives and its overall economic worth.

Development of a chloroplast expression system for Dunaliella salina.

Dunaliella salina is an innovative expression system due to its distinct advantages such as high salt tolerance, low susceptibility to contamination, and the absence of the cell wall. While nuclear transformation has been extensively studied, research on D. salina chloroplast transformation remains in the preliminary stages. In this study, we established an efficient chloroplast expression system for D. salina using Golden Gate assembly. We developed a D. salina toolkit comprising essential components such as chloroplast-specific promoters, terminators, homologous fragments, and various vectors. We confirmed its functionality by expressing the EGFP protein. Moreover, we detailed the methodology of the entire construction process. This expression system enables the specific targeting of foreign genes through simple homologous recombination, resulting in stable expression in chloroplasts. The toolkit achieved a relatively high transformation efficiency within a shorter experimental cycle. Consequently, the construction and utilization of this toolkit have the potential to enhance the efficiency of transgenic engineering in D. salina and advance the development of microalgal biofactories.

Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a prevalent chronic liver condition. However, the potential therapeutic benefits and underlying mechanism of nicotinate-curcumin (NC) in the treatment of NASH remain uncertain. METHODS: A rat model of NASH induced by a high-fat and high-fructose diet was treated with nicotinate-curcumin (NC, 20, 40 mg·kg- 1), curcumin (Cur, 40 mg·kg- 1) and metformin (Met, 50 mg·kg- 1) for a duration of 4 weeks. The interaction between NASH, Cur and Aldo-Keto reductase family 1 member B10 (AKR1B10) was filter and analyzed using network pharmacology. The interaction of Cur, NC and AKR1B10 was analyzed using molecular docking techniques, and the binding energy of Cur and NC with AKR1B10 was compared. HepG2 cells were induced by Ox-LDL (25 µg·ml- 1, 24 h) in high glucose medium. NC (20µM, 40µM), Cur (40µM) Met (150µM) and epalrestat (Epa, 75µM) were administered individually. The activities of ALT, AST, ALP and the levels of LDL, HDL, TG, TC and FFA in serum were quantified using a chemiluminescence assay. Based on the changes in the above indicators, score according to NAS standards. The activities of Acetyl-CoA and Malonyl-CoA were measured using an ELISA assay. And the expression and cellular localization of AKR1B10 and Acetyl-CoA carboxylase (ACCα) in HepG2 cells were detected by Western blotting and immunofluorescence. RESULTS: The results of the animal experiments demonstrated that NASH rat model induced by a high-fat and high-fructose diet exhibited pronounced dysfunction in liver function and lipid metabolism. Additionally, there was a significant increase in serum levels of FFA and TG, as well as elevated expression of AKR1B10 and ACCα, and heightened activity of Acetyl-CoA and Malonyl-CoA in liver tissue. The administration of NC showed to enhance liver function in rats with NASH, leading to reductions in ALT, AST and ALP levels, and decrease in blood lipid and significant inhibition of FFA and TG synthesis in the liver. Network pharmacological analysis identified AKR1B10 and ACCα as potential targets for NASH treatment. Molecular docking studies revealed that both Cur and NC are capable of binding to AKR1B10, with NC exhibiting a stronger binding energy to AKR1B10. Western blot analysis demonstrated an upregulation in the expression of AKR1B10 and ACCα in the liver tissue of NASH rats, accompanied by elevated Acetyl-CoA and Malonyl-CoA activity, and increased levels of FFA and TG. The results of the HepG2 cell experiments induced by Ox-LDL suggest that NC significantly inhibited the expression and co-localization of AKR1B10 and ACCα, while also reduced levels of TC and LDL-C and increased level of HDL-C. These effects are accompanied by a decrease in the activities of ACCα and Malonyl-CoA, and levels of FFA and TG. Furthermore, the impact of NC appears to be more pronounced compared to Cur. CONCLUSION: NC could effectively treat NASH and improve liver function and lipid metabolism disorder. The mechanism of NC is related to the inhibition of AKR1B10/ACCα pathway and FFA/TG synthesis of liver.

Analysis of tumor microenvironment alterations in partially responsive rectal cancer patients treated with neoadjuvant chemoradiotherapy.

PURPOSE: Achieving a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT) remains a challenge for most patients with rectal cancer. Exploring the potential of combining NCRT with immunotherapy or targeted therapy for those achieving a partial response (PR) offers a promising avenue to enhance treatment efficacy. This study investigated the impact of NCRT on the tumor microenvironment in locally advanced rectal cancer (LARC) patients who exhibited a PR. METHODS: This was a retrospective, observational study. Five patients demonstrating a PR after neoadjuvant treatment for LARC were enrolled in the study. Biopsy samples before treatment and resected specimens after treatment were stained with a panel of 26 antibodies targeting various immune and tumor-related markers, each labeled with distinct metal tags. The labeled samples were then analyzed using the Hyperion imaging system. RESULTS: Heterogeneity within the tumor microenvironment was observed both before and after NCRT. Notably, tumor-associated macrophages, CD4 + T cells, CD8 + T cells, CD56 + natural killer cells, tumor-associated neutrophils, cytokeratin, and E-cadherin exhibited slight increase in abundance within the tumor microenvironment following treatment (change ratios = 0.78, 0.2, 0.27, 0.32, 0.17, 0.46, 0.32, respectively). Conversely, the number of CD14 + monocytes, CD19 + B cells, CD45 + CD4 + T cells, collagen I, α-smooth muscle actin, vimentin, and ß-catenin proteins displayed significant decreases post-treatment (change ratios = 1.73, 1.92, 1.52, 1.25, 1.52, 1.12, 2.66, respectively). Meanwhile, Foxp3 + regulatory cells demonstrated no significant change (change ratio = 0.001). CONCLUSIONS: NCRT has diverse effects on various components of the tumor microenvironment in LARC patients who achieve a PR after treatment. Leveraging combination therapies may optimize treatment outcomes in this patient population.

The Anti-Neuroinflammatory Effect of Extra-Virgin Olive Oil in the Triple Transgenic Mouse Model of Alzheimer's Disease.

Background: Chronic intake of extra virgin olive oil is beneficial for brain health and protects from age-related cognitive decline and dementia, whose most common clinical manifestation is Alzheimer's disease. Besides the classical pathologic deposits of amyloid beta peptides and phosphorylated tau proteins, another frequent feature of the Alzheimer's brain is neuroinflammation. Objective: In the current study, we assessed the effect that extra virgin olive oil has on neuroinflammation when administered to a mouse model of the disease. Methods: Triple transgenic mice were randomized to receive a diet enriched with extra virgin olive oil or regular diet for 8 weeks. At the end of this treatment period the expression level of several inflammatory biomarkers was assessed in the central nervous system. Results: Among the 79 biomarkers measured, compared with the control group, mice receiving the extra virgin olive oil had a significant reduction in MIP-2, IL-17E, IL-23, and IL-12p70, but an increase in IL-5. To validate these results, specific ELISA kits were used for each of them. Confirmatory results were obtained for MIP-2, IL-17E, IL-23, and IL-12-p70. No significant differences between the two groups were observed for IL-5. Conclusions: Our results demonstrate that chronic administration of extra virgin olive oil has a potent anti-neuroinflammatory action in a model of Alzheimer's disease. They provide additional pre-clinical support and novel mechanistic insights for the beneficial effect that this dietary intervention has on brain health and dementia.

Carboxymethylated Lycium barbarum seed dreg dietary fiber alleviates high fat diet-induced hyperlipidemia in mice via intestinal regulation.

In this study, we investigated the ameliorative gut modulatory effect of carboxymethylated Lycium barbarum seed dreg insoluble dietary fiber (LBSDIDF) on hyperlipidemic mice. After seven weeks of insoluble dietary fiber (IDF) intervention, the results demonstrated that IDFs effectively inhibited body weight gain, with slimming and hypolipidemic effects, and improved liver histopathology by decreasing ALT, AST, TNF-α and IL-6, and increasing short-chain fatty acid (SCFA) levels in hyperlipidemic mice. With the increasing diversity and abundance of intestinal bacteria and decreasing ratio of Firmicutes to Bacteroidetes, intestinal flora facilitated cholesterol lowering effects in hyperlipidemic mice. Our research offers a novel concept for the use of LBSDIDF as a prebiotic to improve intestinal dysbiosis or as a preventive measure against obesity and dyslipidemia.

A Cysteinyl-tRNA Synthetase Mutation Causes Novel Autosomal-Dominant Inheritance of a Parkinsonism/Spinocerebellar-Ataxia Complex.

This study aimed to identify possible pathogenic genes in a 90-member family with a rare combination of multiple neurodegenerative disease phenotypes, which has not been depicted by the known neurodegenerative disease. We performed physical and neurological examinations with International Rating Scales to assess signs of ataxia, Parkinsonism, and cognitive function, as well as brain magnetic resonance imaging scans with seven sequences. We searched for co-segregations of abnormal repeat-expansion loci, pathogenic variants in known spinocerebellar ataxia-related genes, and novel rare mutations via whole-genome sequencing and linkage analysis. A rare co-segregating missense mutation in the CARS gene was validated by Sanger sequencing and the aminoacylation activity of mutant CARS was measured by spectrophotometric assay. This pedigree presented novel late-onset core characteristics including cerebellar ataxia, Parkinsonism, and pyramidal signs in all nine affected members. Brain magnetic resonance imaging showed cerebellar/pons atrophy, pontine-midline linear hyperintensity, decreased rCBF in the bilateral basal ganglia and cerebellar dentate nucleus, and hypo-intensities of the cerebellar dentate nuclei, basal ganglia, mesencephalic red nuclei, and substantia nigra, all of which suggested neurodegeneration. Whole-genome sequencing identified a novel pathogenic heterozygous mutation (E795V) in the CARS gene, meanwhile, exhibited none of the known repeat-expansions or point mutations in pathogenic genes. Remarkably, this CARS mutation causes a 20% decrease in aminoacylation activity to charge tRNACys with L-cysteine in protein synthesis compared with that of the wild type. All family members carrying a heterozygous mutation CARS (E795V) had the same clinical manifestations and neuropathological changes of Parkinsonism and spinocerebellar-ataxia. These findings identify novel pathogenesis of Parkinsonism-spinocerebellar ataxia and provide insights into its genetic architecture.

Antiviral C-geranylated flavonoids from Artocarpus communis.

Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.

Neurophysiological features of STN LFP underlying sleep fragmentation in Parkinson's disease.

BACKGROUND: Sleep fragmentation is a persistent problem throughout the course of Parkinson's disease (PD). However, the related neurophysiological patterns and the underlying mechanisms remained unclear. METHOD: We recorded subthalamic nucleus (STN) local field potentials (LFPs) using deep brain stimulation (DBS) with real-time wireless recording capacity from 13 patients with PD undergoing a one-night polysomnography recording, 1 month after DBS surgery before initial programming and when the patients were off-medication. The STN LFP features that characterised different sleep stages, correlated with arousal and sleep fragmentation index, and preceded stage transitions during N2 and REM sleep were analysed. RESULTS: Both beta and low gamma oscillations in non-rapid eye movement (NREM) sleep increased with the severity of sleep disturbance (arousal index (ArI)-betaNREM: r=0.9, p=0.0001, sleep fragmentation index (SFI)-betaNREM: r=0.6, p=0.0301; SFI-gammaNREM: r=0.6, p=0.0324). We next examined the low-to-high power ratio (LHPR), which was the power ratio of theta oscillations to beta and low gamma oscillations, and found it to be an indicator of sleep fragmentation (ArI-LHPRNREM: r=-0.8, p=0.0053; ArI-LHPRREM: r=-0.6, p=0.0373; SFI-LHPRNREM: r=-0.7, p=0.0204; SFI-LHPRREM: r=-0.6, p=0.0428). In addition, long beta bursts (>0.25 s) during NREM stage 2 were found preceding the completion of transition to stages with more cortical activities (towards Wake/N1/REM compared with towards N3 (p<0.01)) and negatively correlated with STN spindles, which were detected in STN LFPs with peak frequency distinguishable from long beta bursts (STN spindle: 11.5 Hz, STN long beta bursts: 23.8 Hz), in occupation during NREM sleep (ß=-0.24, p<0.001). CONCLUSION: Features of STN LFPs help explain neurophysiological mechanisms underlying sleep fragmentations in PD, which can inform new intervention for sleep dysfunction. TRIAL REGISTRATION NUMBER: NCT02937727.

Effect of negative pressure therapy on the treatment response to scar thickness and viscoelasticity.

Patients with scars face a grave threat to their mental and physical health. Negative pressure has been used for scar therapy in medical care and provides a microenvironment conducive to scar healing while stimulating cell regeneration. Negative pressure may disrupt scar tissue regeneration when the pressure is too high or too low, so finding a suitable negative pressure is important. We hypothesized that different negative pressure magnitudes would affect scar tissue properties differently. This research aimed to provide practical recommendations for scar therapy. This study used three negative pressures (-105 mmHg, -125 mmHg, and -145 mmHg) to compare scar material properties. We measured scar tissue thickness and viscoelasticity with a motor-driven ultrasound indentation system. According to the results of this study, scar thickness is most effectively reduced at a negative pressure of -105 mmHg. In comparison, scar viscoelasticity continuously increases at a negative pressure of -125 mmHg. Negative pressure therapy can be recommended to scar care clinics based on the results of this study.

Network analysis reveals context-dependent structural complexity of social calls in serrate-legged small treefrogs.

Vocal communication plays an important role in survival, reproduction, and animal social association. Birds and mammals produce complex vocal sequence to convey context-dependent information. Vocalizations are conspicuous features of the behavior of most anuran species (frogs and toads), and males usually alter their calling strategies according to ecological context to improve the attractiveness/competitiveness. However, very few studies have focused on the variation of vocal sequence in anurans. In the present study, we used both conventional method and network analysis to investigate the context-dependent vocal repertoire, vocal sequence, and call network structure in serrate-legged small treefrogs Kurixalus odontotarsus. We found that male K. odontotarsus modified their vocal sequence by switching to different call types and increasing repertoire size in the presence of a competitive rival. Specifically, compared with before and after the playback of advertisement calls, males emitted fewer advertisement calls, but more aggressive calls, encounter calls, and compound calls during the playback period. Network analysis revealed that the mean degree, mean closeness, and mean betweenness of the call networks significantly decreased during the playback period, which resulted in lower connectivity. In addition, the increased proportion of one-way motifs and average path length also indicated that the connectivity of the call network decreased in competitive context. However, the vocal sequence of K. odontotarsus did not display a clear small-world network structure, regardless of context. Our study presents a paradigm to apply network analysis to vocal sequence in anurans and has important implications for understanding the evolution and function of sequence patterns.

A Single-Arm Multi-Center Phase II Clinical Trial of Cadonilimab (anti-PD-1/CTLA-4) in Combination with or without Conventional Second-Line Treatment for Patients with Extensive Stage Small Cell Lung Cancer.

BACKGROUND: Cadonilimab (AK104) is a bispecific IgG-single-chain Fv fragment (ScFv) antibody that binds to PD-1 and CTLA-4. Cadonilimab has shown encouraging anti-tumour activity and a favourable safety profile in several tumour types. In second-line treatment, there is no defined standard of care for patients with extensive-stage small-cell lung cancer (ES-SCLC). Cadonilimab is expected to show substantial clinical efficacy. OBJECTIVE: To assess the antitumor activity and safety of cadonilimab monotherapy or combination with conventional therapy in ES-SCLC patients who failed first-line treatment. METHODS: In this multicenter, open-label, phase II study, ES-SCLC patients who had failed first-line treatment, also aged 18 years to 70 years with histologically or cytologically confirmed ES-SCLC, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2 were eligible. Patients will receive cadonilimab 10 mg/kg every three weeks (Q3 W) among 24 months until progressive disease (PD) or adverse events (AE) discovery. The primary endpoint is progression-free survival (PFS). TRIAL REGISTRATION: NCT05901584.

Interfacial Engineering of MoS2@CoS2 Heterostructure Electrocatalysts for Effective pH-Universal Hydrogen Evolution Reaction.

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.