Photo-Thermal Conversion and Raman Sensing Properties of Three-Dimensional Gold Nanostructure.

Three-dimensional plasma nanostructures with high light-thermal conversion efficiency show the prospect of industrialization in various fields and have become a research hotspot in areas of light-heat utilization, solar energy capture, and so on. In this paper, a simple chemical synthesis method is proposed to prepare gold nanoparticles, and the electrophoretic deposition method is used to assemble large-area three-dimensional gold nanostructures (3D-GNSs). The light-thermal water evaporation monitoring and surface-enhanced Raman scattering (SERS) measurements of 3D-GNSs were performed via theoretical simulation and experiments. We reveal the physical processes of local electric field optical enhancement and the light-thermal conversion of 3D-GNSs. The results show that with the help of the efficient optical trapping and super-hydrophilic surface properties of 3D-GNSs, they have a significant effect in accelerating water evaporation, which was increased by nearly eight times. At the same time, the three-dimensional SERS substrates based on gold nanosphere particles (GNSPs) and gold nanostar particles (GNSTs) had limited sensitivities of 10-10 M and 10-12 M to R6G molecules, respectively. Therefore, 3D-GNSs show strong competitiveness in the fields of solar-energy-induced water purification and the Raman trace detection of organic molecules.

Properties of phosphorus-boron co-doped c-Si quantum dots/SiNx:H thin film prepared by PECVD in-situ deposition.

Co-doping of phosphorus and boron elements into crystalline silicon quantum dot (c-Si QD) is an effective approach for enhancing the photoluminescence (PL) performance. In this paper, we report on the preparation of hydrogenated silicon nitride (SiNx:H) thin films embedded with phosphorus-boron co-doped c-Si QDs via plasma enhanced chemical vapor deposition route. Mixed dilution including hydrogen (H2) and argon (Ar) is applied in the in-situ deposition process for optimizing the deposition process. The P-B co-doped c-Si QD/SiNx:H thin films exhibit a wide range of PL spectra. The emission is greatly improved especially for the short-wavelength light when compared to the SiOx:H thin film containing P-B co-doped c-Si QDs. The effects of H2/Ar flow ratio on the structural and optical characteristics of thin films are systematically investigated through a series of characterizations. Experimental results show that various properties, such as crystallinity, QD size, optical band gap and doping concentrations, are effectively controlled by tuning H2/Ar flow ratio. Based on the red-shift of QCE-related PL peak, the successful P-B co-doping into Si QDs are verified. Finally, a comprehensive discussion has been made to analyze the influence of H2-Ar mixed dilution on the film growth and impurity doping in detail in this paper.

Compressible effect on the mutual interaction of two cavitation bubbles in radial oscillations and translational motion.

In this study, we considered the compressible effect on the mutual interaction of two cavitation bubbles by correcting the sound field emitted by one bubble in the radial equations of the other bubble to first order in the Mach number of the flow, and the effect is represented by the incident wave acting on bubbles. The results illustrates that the incident wave can enhance the resonance response at the redistributed resonance frequency, which leads to an increase in radial acceleration and the secondary Bjerknes force, and rapid approach of bubbles. Furthermore, the influence of incident wave on the interaction of bubbles driven at lower frequencies is more significant, due to resonance enhancement caused by the proximity of natural frequencies and frequency multiplications of the external sound field. Our findings reveal that the compressible effect is not only critical to interaction in radial oscillations, but also in translational motion.

Blockade of LAG-3 and PD-1 leads to co-expression of cytotoxic and exhaustion gene modules in CD8+ T cells to promote antitumor immunity.

Relatlimab (rela; anti-LAG-3) plus nivolumab (nivo; anti-PD-1) is safe and effective for treatment of advanced melanoma. We designed a trial (NCT03743766) where advanced melanoma patients received rela, nivo, or rela+nivo to interrogate the immunologic mechanisms of rela+nivo. Analysis of biospecimens from this ongoing trial demonstrated that rela+nivo led to enhanced capacity for CD8+ T cell receptor signaling and altered CD8+ T cell differentiation, leading to heightened cytotoxicity despite the retention of an exhaustion profile. Co-expression of cytotoxic and exhaustion signatures was driven by PRDM1, BATF, ETV7, and TOX. Effector function was upregulated in clonally expanded CD8+ T cells that emerged after rela+nivo. A rela+nivo intratumoral CD8+ T cell signature was associated with a favorable prognosis. This intratumoral rela+nivo signature was validated in peripheral blood as an elevated frequency of CD38+TIM3+CD8+ T cells. Overall, we demonstrated that cytotoxicity can be enhanced despite the retention of exhaustion signatures, which will inform future therapeutic strategies.

Linear relationships between aboveground biomass and plant species diversity during the initial stage of degraded grassland restoration projects.

The relationship between aboveground biomass and plant diversity has been extensively examined to understand the role of biodiversity in ecosystem functions and services. Degraded grassland restoration projects can enhance carbon sequestration. However, the relationship between biomass and diversity remains one of the most actively debated topics regarding grassland ecosystems in degraded grassland restoration projects. We speculated that establishing the linear relationships between aboveground biomass and plant species diversity could contribute to enhancing the efficacy of degraded grassland restoration projects. This study sought to determine whether these relationships were linear during the initial stages of the restoration projects of degraded grasslands in Xing'an League, China. The investigations were based on an examination of seventy-six 1 × 1 m2 plots distributed among 15 areas in which the degraded grassland was at the initial stages of restoration. To quantify the species diversity of the degraded grassland communities, we used the species richness, Shannon-Wiener, inverse Simpson's reciprocal, and Pielou's evenness indices. Our analyses revealed that aboveground biomass had clear positive linear relationships with species richness during the initial stages of degraded grassland restoration. However, there were less pronounced associations with species diversity as assessed using the Shannon and inverse Simpson indices, based on regression models. Furthermore, weed biomass was found to have significant negative effects on species richness and Pielou's evenness. The weak linear relationship between aboveground biomass and species richness could be ascribed to an increase in weed biomass. We concluded that aboveground biomass and plant species diversity could be enhanced during the initial stages of degraded grassland restoration projects and suggest that the extent of weed biomass could serve as a key indicator of the efficacy of restoration from the perspective of plant species diversity and aboveground biomass in carbon sequestration projects.

Effect of Common Cold on Serum Clozapine Concentrations in Hospitalized Patients with Schizophrenia.

Objective: The present study aims to investigate the effect of common cold on the serum clozapine concentrations in hospitalized patients with schizophrenia. Methods: A total of 65 schizophrenic patients with common cold receiving clozapine treatment were retrospectively enrolled. The demographic data, medication situation, clozapine concentration, and parameters of routine haematological and biochemical laboratory tests were obtained from the medical record system. The serum clozapine concentration and clozapine concentration/dose (C/D) ratios between the baseline period and cold period were compared by paired-sample t tests. Association between the changes in serum concentration and C/D ratios of clozapine and changes in white blood cell (WBC) and neutrophil (NE) counts was evaluated using Pearson correlation analysis. Results: The serum clozapine concentration (t = -9.856, P < 0.001) and clozapine C/D ratios (t = -10.071, P < 0.001) were found to be significantly elevated in the cold period compared to the baseline period. Moreover, the changes in the serum clozapine concentration were found to be significantly elevated in female patients compared to male patients (t = -2.483, P = 0.017). Furthermore, changes in the serum clozapine concentration were positively correlated to the changes in WBC (r = 0.303, P = 0.014) and NE (r = 0.315, P = 0.011) counts. Similarly, changes in clozapine C/D ratios were positively correlated to the changes in WBC (r = 0.275, P = 0.027) and NE (r = 0.328, P = 0.008) counts. Conclusion: The serum clozapine concentrations in patients with schizophrenia during the common cold period were increased, which might by related to the elevated WBC and NE counts.

The association between alcohol consumption and herpes simplex virus type 2: A cross-sectional study from national health and nutrition examination survey 2009-2016.

BACKGROUND: The current prevalence of Herpes simplex virus type 2 (HSV-2) infection is notably high, with individuals afflicted by HSV-2 facing recurrent outbreaks, challenges in achieving remission, and an elevated risk of HIV infection. This study aims to investigate the relationship between alcohol consumption and HSV-2 infection. METHODS: The data for this study were sourced from 7257 participants who took part in the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2016. The target population consisted of adults with reliable HSV-2 plasma results, and alcohol consumption was assessed using self-report methods. We evaluated the odds ratio (OR) and 95% confidence interval (CI) for the association between alcohol consumption and HSV-2 infection. These estimations were derived from a logistic regression model that was adjusted for key confounding factors. Subgroup analysis specifically focused on alcohol consumption, and the interaction between HSV-2 infection, alcohol consumption, and other variables was assessed through stratified analysis. RESULTS: Among the 7,257 participants included, 89.8% (6,518/7,257) reported varying levels of alcohol consumption history. Compared to individuals who never drinkers, the adjusted odds ratios (ORs) for former drinkers, light drinkers, moderate drinkers, and heavy drinkers were 1.79 (95% CI: 1.34-2.4, p < 0.001), 1.38 (95% CI: 1.07-1.77, p = 0.012), 1.49 (95% CI: 1.15-1.94, p = 0.003), and 1.47 (95% CI: 1.14-1.9, p = 0.003), respectively. The results remained stable in subgroup analyses and sensitivity analyses. CONCLUSION: Current research indicates that individuals with a history of alcohol consumption exhibit a higher risk of HSV-2 infection compared to those who have never drinkers.

Evaluation of plasma-derived extracellular vesicles miRNAs and their connection with hippocampal mRNAs in alcohol use disorder.

Alcohol use disorder (AUD) is a common mental illness with high morbidity and disability. The discovery of laboratory biomarkers has progressed slowly, resulting in suboptimal diagnosis and treatment of AUD. This study aimed to identify promising biomarkers, as well as the potential miRNA-mRNA networks associated with AUD pathogenesis. RNA sequencing was performed on plasma-derived small extracellular vesicles (sEVs) from AUD patients and healthy controls (HCs) to harvest miRNAs expression profiles. Machine learning (ML) models were built to screen characteristic miRNAs, whose target mRNAs were analyzed using TargetScan, miRanda and miRDB databases. Gene Expression Omnibus (GEO) datasets (GSE181804 and GSE180722) providing postmortem hippocampal gene expression profiles of AUD subjects were mined. A total of 247 differentially expressed (DE) plasma-derived sEVs miRNAs and 122 DE hippocampal mRNAs were obtained. Then, 22 overlapping sEVs miRNAs with high importance scores were gained by intersecting 5 ML models. As a result, we established a putative sEVs miRNA-hippocampal mRNA network that can effectively distinguish AUD patients from HCs. In conclusion, we proposed 5 AUD-representative sEVs miRNAs (hsa-miR-144-5p, hsa-miR-182-5p, hsa-miR-142-5p, hsa-miR-7-5p, and hsa-miR-15b-5p) that may participate in the pathogenesis of AUD by modulating downstream target hippocampal genes. These findings may provide novel insights into the diagnosis and treatment of AUD.

Effect of duloxetine on changes in serum proinflammatory cytokine levels in patients with major depressive disorder.

OBJECTIVE: Accumulating evidence supports the idea that inflammation may contribute to the pathophysiology of major depressive disorder (MDD). Duloxetine, a serotonin-norepinephrine reuptake inhibitor, exhibits anti-inflammatory effects both in vitro and in vivo. In this study, we investigated the impact of duloxetine on changes in serum proinflammatory cytokine levels among individuals diagnosed with MDD. METHODS: A cohort of 23 drug-naïve individuals diagnosed with MDD and 23 healthy controls were included in this study. The severity of depressive symptoms was evaluated using the 24-item Hamilton Depression Scale (HAMD-24). A panel of 7 proinflammatory cytokines, including interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), were quantified using multiplex Luminex assays. The levels of serum cytokines in healthy controls and patients with MDD were compared at baseline. All patients received duloxetine at a dosage range of 40-60 mg/day for a duration of 4 weeks. The HAMD-24 scores and serum cytokine levels were compared before and after duloxetine treatment. RESULTS: Compared with healthy controls, patients with MDD had significantly greater levels of IL-2, IL-6, IL-8, IL-12, TNF-α, and IFN-γ (P < 0.05). Moreover, there was a significant decrease in HAMD-24 scores observed pre- and post-treatment (t = 13.161, P < 0.001). Furthermore, after 4 weeks of treatment, the serum levels of IL-8 (t = 3.605, P = 0.002), IL-12 (t = 2.559, P = 0.018), and IFN-γ (t = 3.567, P = 0.002) decreased significantly. However, there were no significant differences in other cytokines, including IL-1ß, IL-2, IL-6, and TNF-α, before and after treatment (P > 0.05). CONCLUSIONS: These findings present compelling evidence, potentially for the first time, indicating that duloxetine treatment may effectively reduce the serum concentrations of IL-8, IL-12, and IFN-γ in individuals diagnosed with MDD. However, the precise mechanisms underlying this effect remain unclear and warrant further investigation.

[Evaluation of the effect of MTF-S on the removal of impacted mandibular wisdom teeth with complete or partial crown impaction].

PURPOSE: To evaluation the effect of modified triangular flap-secondary healing (MTF-S) on the treatment of mandibular impacted wisdom teeth with full or partial bone impaction. METHODS: A total of 207 patients with mandibular impacted wisdom teeth were selected in Shaoxing Stomatological Hospital from June 2022 to June 2023. Among them, 86 patients had completely impacted wisdom teeth (group A), and 121 patients had partially impacted wisdom teeth (group B). All patients had bilateral impacted wisdom teeth. One of the wisdom teeth was removed first and was sutured with triangular flap-primary healing (TF-P). The other wisdom tooth was removed two weeks later and was sutured with MTF-S. Patients in groups A and B were divided into two subgroups based on suture methods, with TF-P used for group A1 and B1, and MTF-S used for groups A2 and B2. Perioperative indicators, including surgical time, root loss rate, and completeness of extraction sockets were recorded; Postoperative complications of four groups, including pain, swelling, and limited mouth opening were compared. SPSS 22.0 software package was used for statistical analysis. RESULTS: The surgical time of group A1, A2, B1 and B2 was (17.69±3.28), (18.22±3.06), (12.37±3.72) and (12.64±4.13) minutes, respectively. The surgical time of group A1 and A2 was significantly longer than that of group B1 and B2 (P＜0.05). Seven days after surgery, the VAS scores of group A1, A2, B1 and B2 were (1.17±0.34), (0.93±0.29), (0.48±0.15) and (0.76±0.21), respectively. The VAS scores of group B1 and B2 were lower than those of group A1 and A2, and group A2 was lower than group A1 and B2 was higher than group B1 group(P＜0.05). On the 1st day, 3rd day, and 7th day after surgery, the swelling degree in group A1 was greater than that in group B1, and the swelling degree in group B1 was greater than that in group A2 and B2(P＜0.05); while the limitation of mouth opening mouth in group A2 and B2 was lower than that in group A1 and B1, and the limitation of opening mouth in group B2 was lower than that in group A2(P＜0.05). CONCLUSIONS: Compared with partially impacted wisdom teeth, the extraction of completely impacted wisdom teeth has a longer surgical time. For completely impacted wisdom teeth, MTF-S is beneficial for reducing postoperative pain, swelling and mouth opening limitations. For partially impacted wisdom teeth, MTF-S is beneficial for reducing postoperative swelling and mouth opening limitations, but the effect is not significant in reducing patient pain.

Prognostic and immunotherapeutic potential of regulatory T cell-associated signature in ovarian cancer.

Tumour-induced immunosuppressive microenvironments facilitate oncogenesis, with regulatory T cells (Tregs) serving as a crucial component. The significance of Treg-associated genes within the context of ovarian cancer (OC) remains elucidated insufficiently. Utilizing single-cell RNA sequencing (scRNA-Seq) for the identification of Treg-specific biomarkers, this investigation employed single-sample gene set enrichment analysis (ssGSEA) for the derivation of a Treg signature score. Weighted gene co-expression network analysis (WGCNA) facilitated the identification of Treg-correlated genes. Machine learning algorithms were employed to determine an optimal prognostic model, subsequently exploring disparities across risk strata in terms of survival outcomes, immunological infiltration, pathway activation and responsiveness to immunotherapy. Through WGCNA, a cohort of 365 Treg-associated genes was discerned, with 70 implicated in the prognostication of OC. A Tregs-associated signature (TAS), synthesized from random survival forest (RSF) and Least Absolute Shrinkage and Selection Operator (LASSO) algorithms, exhibited robust predictive validity across both internal and external cohorts. Low TAS OC patients demonstrated superior survival outcomes, augmented by increased immunological cell infiltration, upregulated immune checkpoint expression, distinct pathway enrichment and differential response to immunotherapeutic interventions. The devised TAS proficiently prognosticates patient outcomes and delineates the immunological milieu within OC, offering a strategic instrument for the clinical stratification and selection of patients.

Cytokine profile in first-episode drug-naïve major depressive disorder patients with or without anxiety.

OBJECTIVE: It is known that cytokines play a role in both depression and anxiety. This study aimed to compare the levels of multiple cytokines in patients with first-episode drug-naive major depressive disorder (MDD) with or without anxiety and analyze the correlation between the level of depression or anxiety and the serum cytokine levels. METHODS: The study involved 55 patients with first-episode drug-naive MDD. To assess anxiety symptoms, the 14-item HAMA was used. MDD patients were divided into two groups: 23 MDD patients without anxiety and 32 MDD patients with anxiety. The measurement of 37 cytokines was conducted. Serum cytokine levels between patients with MDD without anxiety and anxiety were compared. In multiple linear regression models, the relationship between the group and abnormal cytokines was explored. The receiver operating characteristic (ROC) curve analysis was performed to estimate diagnostic performance of serum cytokines in discriminating MDD patients with anxiety from MDD patients without anxiety. A correlation was evaluated between the scores of HAMD or HAMA and the serum cytokine levels. RESULTS: In MDD patients with anxiety, IL-17 C and CCL17 levels were significantly lower than in MDD patients without anxiety (all P < 0.05). Multiple measurements were corrected with Benjamini-Hochberger corrections, but none of these differences persisted (all P > 0.05). The results of multiple linear regression models revealed that after controlling for other independent variables, group was not a significant independent predictor of serum IL-17 C or CCL17 (all P > 0.05). The AUC values of IL-17 C and CCL17 were 0.643 and 0.637, respectively, in discriminating MDD patients with anxiety from MDD patients without anxiety. The results of partial correlation analyses showed the scores of HAMD were negatively correlated with the IL-17 C (r = -0.314, P = 0.021) levels with sex as a covariate. CONCLUSIONS: The findings suggest that there is a potential absence of disparity in the levels of circulating cytokines among individuals diagnosed with first-episode drug-naïve MDD, regardless of the presence or absence of comorbid anxiety.

Serum indoleamine 2, 3-dioxygenase and tryptophan-2, 3-dioxygenase: potential biomarkers for the diagnosis of major depressive disorder.

OBJECTIVE: The objective of this study was to observe the changes in the levels of indoleamine 2, 3-dioxygenase (IDO) and tryptophan-2, 3-dioxygenase (TDO) in patients with major depressive disorder (MDD) and investigate their potential role as novel biomarkers for diagnosing MDD. METHODS: A total of 55 MDD patients and 55 healthy controls (HC) were enrolled in the study. The severity of MDD was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24) before and after treatment. The serum concentrations of IDO and TDO were measured at baseline and after treatment. The correlations between the serum levels of IDO and TDO and HAMD-24 scores were evaluated using Pearson's correlation test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the area under the curve (AUC) of serum levels of IDO and TDO for discriminating MDD patients from HC. RESULTS: The serum IDO and TDO concentrations were significantly higher in patients with MDD at baseline than in healthy controls, and decreased significantly after 2 weeks or 1 month of treatment. The levels of IDO and TDO were significantly positively correlated with HAMD-24 scores. Furthermore, the AUC values for IDO and TDO were 0.999 and 0.966, respectively. CONCLUSION: The study suggests that serum IDO and TDO may serve as novel biomarkers for diagnosing MDD. These findings may lead to a better understanding of the pathogenesis of MDD and the development of new therapeutic targets.

REG3A promotes proliferation and DDP resistance of ovarian cancer cells by activating the PI3K/Akt signaling pathway.

This study explored the effect of Regenerating Islet-Derived 3-Alpha (REG3A) on ovarian cancer (OC) progression. REG3A expression was scrutinized in clinical tissues of 97 OC cases by quantitative real-time polymerase chain reaction (qRT-PCR). REG3A expression in OC cells and cisplatin (DDP) resistance OC cells was regulated by transfection. LY294002 (10 µM, inhibitor of the PI3K/Akt signaling pathway) was used to treat OC cells and DDP resistance OC cells. Cell counting kit-8 and methyl-thiazolyl-tetrazolium assays were applied for proliferation and DDP resistance detection. Flow cytometry was utilized for cell cycle and apoptosis analysis. The effect of REG3A on the OC cell in vivo growth was researched by establishing xenograft tumor model via using nude mice using nude mice. The expression of genes in clinical samples, cells and xenograft tumor tissues was investigated by qRT-PCR, Western blot and immunohistochemistry. As a result, REG3A was over-expressed in OC patients and cells, associating with dismal prognosis of patients. REG3A knockdown repressed proliferation, DDP resistance, induced cell cycle arrest and apoptosis of OC cells, and reduced the expression MDR-1, Cyclin D1, Cleaved caspase 3 proteins and the PI3K/Akt signaling pathway activity in OC cells. LY294002 treatment abrogated the promotion effect of REG3A on OC cell proliferation, apoptosis inhibition and DDP resistance. REG3A knockdown suppressed the in vivo growth of OC cells. Thus, REG3A promoted proliferation and DDP resistance of OC cells by activating the PI3K/Akt signaling pathway. REG3A might be a promising target for the clinical treatment of OC.

Develop an undergraduate curriculum for nursing engineering with Delphi method / 现代临床护理

Objective To develop an undergraduate curriculum for nursing engineering hence to provide a reference for establishing an innovative thinking of nursing undergraduates and cultivating innovative talents with interdisciplinary knowledge in nursing and engineering.Methods Based on literatures review,the primary undergraduate curriculum for nursing engineering was drafted through the expert focus method.With the Delphi method,20 experts were engaged in two rounds of correspondence consultation to finalise the curriculum.Results The response rate from two rounds of expert consultation was 100.00%,with an expert authority coefficient of 0.855.Of the first and second round of consultations,the coefficient of variation of each item was 0.09-0.28 and 0.08-0.24,respectively,and the Kendall coordination coefficient was 0.130-0.210 and 0.152-0.350,respectively(all P<0.01).The average importance of each item for the first round of consultation was 3.45 to 4.68,with a standard deviation from 0.51 to 1.14,and it was 3.80 to 4.85 for the second round with a standard deviation from 0.37 to 0.99.Finally,the undergraduate curriculum for nursing engineering was finalised.It included 4 primary indicators,10 secondary indicators and 38 tertiary indicators.Conclusions The developed undergraduate curriculum for nursing engineering meets the requirement of clinical medicine and development in nursing science.The curriculum is authoritative and scientific,therefore it can provide a reference for the training of innovative talents with interdisciplinary knowledge of nursing and engineering in China.

[Research progress on the biological effects of HIF-1α on follicle development and ovulation].

Hypoxia inducible factor-1α (HIF-1α), as a hypoxia inducible factor, affects women's reproductive function by regulating the development and excretion of follicles. HIF-1α induces glycolysis and autophagy in the granule cells by promoting oocyte development, regulating the secretion of related angiogenic factors, and improving follicle maturity. In addition, HIF-1α promotes the process of luteinization of follicular vesicles, maintains luteal function, and finally completes physiological luteal atrophy through cumulative oxidative stress. Dysfunction of HIF-1α will cause a series of pathological consequences, such as angiogenesis defect, energy metabolism abnormality, excessive oxidative stress and dysregulated autophagy and apoptosis, resulting in ovulation problem and infertility. This article summarizes the previous studies on the regulation of follicle development and excretion and maintenance of luteal function and structural atrophy by HIF-1α. We also describe the effective intervention mechanism of related drugs or bioactive ingredients on follicular dysplasia and ovulation disorders through HIF-1α, in order to provide a systematic and in-depth insights for solving ovulation disorder infertility.

Integrated BATF transcriptional network regulates suppressive intratumoral regulatory T cells.

Human regulatory T cells (Tregs) are crucial regulators of tissue repair, autoimmune diseases, and cancer. However, it is challenging to inhibit the suppressive function of Tregs for cancer therapy without affecting immune homeostasis. Identifying pathways that may distinguish tumor-restricted Tregs is important, yet the transcriptional programs that control intratumoral Treg gene expression, and that are distinct from Tregs in healthy tissues, remain largely unknown. We profiled single-cell transcriptomes of CD4+ T cells in tumors and peripheral blood from patients with head and neck squamous cell carcinomas (HNSCC) and those in nontumor tonsil tissues and peripheral blood from healthy donors. We identified a subpopulation of activated Tregs expressing multiple tumor necrosis factor receptor (TNFR) genes (TNFR+ Tregs) that is highly enriched in the tumor microenvironment (TME) compared with nontumor tissue and the periphery. TNFR+ Tregs are associated with worse prognosis in HNSCC and across multiple solid tumor types. Mechanistically, the transcription factor BATF is a central component of a gene regulatory network that governs key aspects of TNFR+ Tregs. CRISPR-Cas9-mediated BATF knockout in human activated Tregs in conjunction with bulk RNA sequencing, immunophenotyping, and in vitro functional assays corroborated the central role of BATF in limiting excessive activation and promoting the survival of human activated Tregs. Last, we identified a suite of surface molecules reflective of the BATF-driven transcriptional network on intratumoral Tregs in patients with HNSCC. These findings uncover a primary transcriptional regulator of highly suppressive intratumoral Tregs, highlighting potential opportunities for therapeutic intervention in cancer without affecting immune homeostasis.

Central sleep apnea treated by a constant low-dose CO2 supplied by a novel device.

CO2 inhalation has been previously reported as a treatment for central sleep apnea both when associated with heart failure or where the cause is unknown. Here, we evaluated a novel CO2 supply system using a novel open mask capable of comfortably delivering a constantly inspired fraction of CO2 ([Formula: see text]) during sleep. We recruited 18 patients with central sleep apnea (13 patients with cardiac disease, and 5 patients idiopathic) diagnosed by diaphragm electromyogram (EMG) recordings made during overnight full polysomnography (PSG) (night 1). In each case, the optimal [Formula: see text] was determined by an overnight manual titration with PSG (night 2). Titration commenced at 1% CO2 and increased by 0.2% increments until central sleep apnea (CSA) disappeared. Patients were then treated on the third night (night 3) with the lowest therapeutically effective concentration of CO2 derived from night 2. Comparing night 1 and night 3, both apnea-hypopnea index (AHI; 31 ± 14 vs. 6 ± 3 events/h, P < 0.01) and arousal index (22 ± 8 vs. 15 ± 8 events/h, P < 0.01) were significantly improved during CO2 treatment. Sleep efficiency improved from 71 ± 18 to 80 ± 11%, P < 0.05, and sleep latency was shorter (23 ± 18 vs. 10 ± 10 min, P < 0.01). Heart rate was not different between night 1 and night 3. Our data confirm the feasibility of our CO2 delivery system and indicate that individually titrated CO2 supplementation with a novel device including a special open mask can reduce sleep disordered breathing severity and improve sleep quality. Randomized controlled studies should now be undertaken to assess therapeutic benefit for patients with CSA.NEW & NOTEWORTHY A novel device using a special mask was developed and proved that CO2 therapy using the device could eliminate central sleep apnea (CSA) events and improve sleep quality including reducing arousal index in patients with heart failure. The device would become a useful clinical treatment for heart failure patients with CSA.

[Effects of moxibustion at "Tianshu"（ST25） and "Shangjuxu" （ST37） on colonic metabolites and inflammatory factors in rats with Crohn's disease].

OBJECTIVE: To observe the effects of moxibustion at "Tianshu"（ST25） and "Shangjuxu"（ST37） on the colonic metabolites and inflammatory factors in rats with Crohn's disease（CD）, so as to explore the mechanisms of moxibustion in protecting colon of CD rats based on metabolomics. METHODS: Twelve rats were first randomly selected from 36 male SD rats as a normal group（NG）. The CD model was induced by 2, 4, 6 trinitrobenzene sulfonic acid（TNBS） enema on the rest 24 rats. After successful modeling, rats were randomly divided into model（TNBS） and moxibustion（TNBS+MOX） groups（n=10 rats/group）. Moxibustion was applied at bilateral ST25 and ST37 for 30 min, once daily for 7 consecutive days in the TNBS+MOX group, while rats in the NG and TNBS groups did not receive any interventions. Body weight of rats was recorded and disease activity index（DAI） was assessed during the experiment. After interventions, HE staining was performed to observe pathological damage of colon. Serum levels of inflammatory factors were measured by ELISA. NMR hydrogen spectroscopy was used to detect colonic metabolites of each group, and orthogonal partial least squares discriminant analysis（OPLS-DA） was used to screen differential colonic metabolites between groups, followed by pathway analysis using MetaboAnalyst 5.0 platform. RESULTS: After modeling, compared with the NG group, the body weight of the rats in the TNBS group was significantly decreased（P<0.05）, the DAI score was increased （P<0.05）, the colon had obvious inflammatory damage and the pathological injury index was increased（P<0.05）, and levels of serum tumor necrosis factor-α（TNF-α）, interleukin（IL）-1ß and interferon-γ（IFN-γ） were significantly increased（P<0.05）. After moxibustion intervention, compared with the TNBS group, the body weight was significantly increased（P<0.05）, while the levels of serum TNF-α, IL-1ß, IFN-γ, and DAI score of the rats in the TNBS+MOX group were significantly decreased（P<0.05）, with alleviated colonic inflammatory injury detected by HE staining. Compared with the NG group, the relative expressions of colonic hypoxanthine, betaine, creatine, inositol, taurine, uracil, and methanol of the TNBS group were decreased（P<0.05）, while the relative expressions of histidine, leucine, proline, lysine, isoleucine, phenylalanine, tyrosine, propionic acid, and valine were increased（P<0.05） in the TNBS group, among which, relative expressions of hypoxanthine, leucine, lysine, isoleucine, betaine, tyrosine, and taurine were reversed in the TNBS+MOX group relevant to the TNBS group, mainly involving phenylalanine, tyrosine and tryptophan biosynthesis, and taurine and subtaurine metabolism pathway. CONCLUSION: The mechanism of moxibustion at ST25 and ST37 for CD may be related to improving colon metabolic disorder state by regulating multiple metabolic metabolites and metabolic pathways, and reducing the level of inflammatory factors, so as to maintain intestinal immune homeostasis.

Peripheral Complement Factor-Based Biomarkers for Patients with First-Episode Schizophrenia.

Objective: Schizophrenia (SCZ) is a severe, protracted neurological disorder that causes disruptive conduct in millions of individuals globally. Discovery of potential biomarkers in clinical settings would lead to the development of efficient diagnostic techniques and an awareness of the disease's pathogenesis and prognosis. The aim of the present study was to discover and identify serum complement factor-based biomarkers in discriminating patients with first-episode SCZ from healthy controls. Methods: Eighty-nine patients with first-episode SCZ and 89 healthy controls were included in this study. Psychiatric symptom severity of patients with SCZ was measured with the Brief Psychiatric Rating Scale-18 Item Version (BPRS) and the Scales for the Assessment of Negative/Positive Symptoms (SANS/SAPS). A total of 5 complement factors including complement component 1 (C1), C2, C3, C4, and 50% hemolytic complement (CH50) were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. The levels of serum complement factors in the SCZ and control groups were compared, and the receiver operating characteristic (ROC) curve method was used to assess the diagnostic values of various complement factors for separating SCZ patients from healthy controls. Pearson's correlation test was used to assess the relationships between serum complement factor concentrations and the psychiatric symptom severity. Results: There was an increase in serum levels of C1, C2, C3, C4, and CH50 among patients with SCZ. Moreover, based on ROC curve analysis, the AUC value of a combined panel of C1, C2, C3, C4, and CH50 was 0.857 when used to discriminate patients with SCZ from healthy controls. Furthermore, serum C2, C3, and CH50 levels were positively correlated to the scores of SANS, SAPS, and BPRS in patients with SCZ, respectively. Conclusion: These results suggested that circulating complement factors including C1, C2, C3, C4, and CH50 may have potential in discovering biomarkers for diagnosing first-episode SCZ.