Wide field-of-view laser-based white light transmitter for visible light communications.

The advancement demands of high-speed wireless data link ask for higher requirements on visible light communication (VLC), where wide coverage stands as a critical criterion. Here, we present the design and implementation of a transmitter structure capable of emitting a high-power wide-coverage white light laser. This laser source exhibits excellent stability, with an irradiation range extending to a half-angle of 20°. Its high brightness satisfies the needs of indoor illumination while maintaining excellent communication performance. Utilizing bit-loading discrete multi-tone modulation, a peak data transmission rate of 3.24 Gbps has been achieved, spanning 1 to 5 m. Remarkably, the data rates exceed 2.5 Gbps within a 40° range at a distance of 5 m, enabling a long-distance, wide coverage, high-speed VLC link for future mobile network applications.

Profiling the interplay and coevolution of Microcystis aeruginosa and cyanosiphophage Mic1.

The cyanosiphophage Mic1 specifically infects the bloom-forming Microcystis aeruginosa FACHB 1339 from Lake Chaohu, China. Previous genomic analysis showed that its 92,627 bp double-stranded DNA genome consists of 98 putative open reading frames, 63% of which are of unknown function. Here, we investigated the transcriptome dynamics of Mic1 and its host using RNA sequencing. In the early, middle, and late phases of the 10 h lytic cycle, the Mic1 genes are sequentially expressed and could be further temporally grouped into two distinct clusters in each phase. Notably, six early genes, including gp49 that encodes a TnpB-like transposase, immediately reach the highest transcriptional level in half an hour, representing a pioneer cluster that rapidly regulates and redirects host metabolism toward the phage. An in-depth analysis of the host transcriptomic profile in response to Mic1 infection revealed significant upregulation of a polyketide synthase pathway and a type III-B CRISPR system, accompanied by moderate downregulation of the photosynthesis and key metabolism pathways. The constant increase of phage transcripts and relatively low replacement rate over the host transcripts indicated that Mic1 utilizes a unique strategy to gradually take over a small portion of host metabolism pathways after infection. In addition, genomic analysis of a less-infective Mic1 and a Mic1-resistant host strain further confirmed their dynamic interplay and coevolution via the frequent horizontal gene transfer. These findings provide insights into the mutual benefit and symbiosis of the highly polymorphic cyanobacteria M. aeruginosa and cyanophages. IMPORTANCE: The highly polymorphic Microcystis aeruginosa is one of the predominant bloom-forming cyanobacteria in eutrophic freshwater bodies and is infected by diverse and abundant cyanophages. The presence of a large number of defense systems in M. aeruginosa genome suggests a dynamic interplay and coevolution with the cyanophages. In this study, we investigated the temporal gene expression pattern of Mic1 after infection and the corresponding transcriptional responses of its host. Moreover, the identification of a less-infective Mic1 and a Mic1-resistant host strain provided the evolved genes in the phage-host coevolution during the multiple-generation cultivation in the laboratory. Our findings enrich the knowledge on the interplay and coevolution of M. aeruginosa and its cyanophages and lay the foundation for the future application of cyanophage as a potential eco-friendly and bio-safe agent in controlling the succession of harmful cyanobacterial blooms.

Synthesis of Size-Adjustable CsPbBr3 Perovskite Quantum Dots for Potential Photoelectric Catalysis Applications.

As a direct band gap semiconductor, perovskite has the advantages of high carrier mobility, long charge diffusion distance, high defect tolerance and low-cost solution preparation technology. Compared with traditional metal halide perovskites, which regulate energy band and luminescence by changing halogen, perovskite quantum dots (QDs) have a surface effect and quantum confinement effect. Based on the LaMer nucleation growth theory, we have synthesized CsPbBr3 QDs with high dimensional homogeneity by creating an environment rich in Br- ions based on the general thermal injection method. Moreover, the size of the quantum dots can be adjusted by simply changing the reaction temperature and the concentration of Br- ions in the system, and the blue emission of strongly confined pure CsPbBr3 perovskite is realized. Finally, optical and electrochemical tests suggested that the synthesized quantum dots have the potential to be used in the field of photocatalysis.

Characterization of humoral immune responses against SARS-CoV-2 accessory proteins in infected patients and mouse model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune response. However, their expressions in infected cells and immunogenicity in infected humans and mice are still not fully understood. In this study, we detected accessory protein-specific antibodies in COVID-19 patients' sera using various techniques, including Luciferase Immunoprecipitation System (LIPS), Immunofluorescence assay (IFA), and Western blot (WB). Proteins 3a, 3b, 7b, 8 and 9c specific antibodies can be detected by LIPS, but only protein 3a antibody was detected by IFA or WB. And antibodies against protein 3a and 7b only detected in ICU patients, which may serve as a marker for predicting the disease progression. Further, we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a, 6, 7a, 8, and 9b. We also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a, 6, 7a, 8, 9b and 9c were able to induce measurable antibody productions, but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 infection. Our findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response, providing a basis for the protein detection assays and their role in pathogenesis.

TPG-functionalized PLGA/PCL nanofiber membrane facilitates periodontal tissue regeneration by modulating macrophages polarization via suppressing PI3K/AKT and NF-κB signaling pathways.

Traditional fibrous membranes employed in guided tissue regeneration (GTR) in the treatment of periodontitis have limitations of bioactive and immunomodulatory properties. We fabricated a novel nTPG/PLGA/PCL fibrous membrane by electrospinning which exhibit excellent hydrophilicity, mechanical properties and biocompatibility. In addition, we investigated its regulatory effect on polarization of macrophages and facilitating the regeneration of periodontal tissue both in vivo and in vitro. These findings showed the 0.5%TPG/PLGA/PCL may inhibit the polarization of RAW 264.7 into M1 phenotype by suppressing the PI3K/AKT and NF-κB signaling pathways. Furthermore, it directly up-regulated the expression of cementoblastic differentiation markers (CEMP-1 and CAP) in periodontal ligament stem cells (hPDLSCs), and indirectly up-regulated the expression of cementoblastic (CEMP-1 and CAP) and osteoblastic (ALP, RUNX2, COL-1, and OCN) differentiation markers by inhibiting the polarization of M1 macrophage. Upon implantation into a periodontal bone defect rats model, histological assessment revealed that the 0.5%TPG/PLGA/PCL membrane could regenerate oriented collagen fibers and structurally intact epithelium. Micro-CT (BV/TV) and the expression of immunohistochemical markers (OCN, RUNX-2, COL-1, and BMP-2) ultimately exhibited satisfactory regeneration of alveolar bone, periodontal ligament. Overall, 0.5%TPG/PLGA/PCL did not only directly promote osteogenic effects on hPDLSCs, but also indirectly facilitated cementoblastic and osteogenic differentiation through its immunomodulatory effects on macrophages. These findings provide a novel perspective for the development of materials for periodontal tissue regeneration.

Efficacy and safety of oral ibrexafungerp in Chinese patients with vulvovaginal candidiasis: a phase III, randomized, double-blind study.

PURPOSE: To evaluate the efficacy and safety of oral ibrexafungerp (HS-10366) versus placebo in Chinese patients with vulvovaginal candidiasis (VVC). METHODS: A double-blind, placebo-controlled, randomized, multicenter phase III study was conducted in symptomatic VVC patients. Patients received (2:1) twice-daily oral ibrexafungerp 300 mg or matching placebo for 1 day. The primary endpoint was clinical cure (vulvovaginal signs and symptoms [VSS] score = 0) at test-of-cure (TOC) on day 11 ± 3. The secondary endpoints included mycological eradication, overall response, and clinical improvement (VSS score ≤ 1) at TOC, and vulvovaginal symptom resolution at follow-up on day 25 ± 4. RESULTS: In total, 360 patients were included in the modified intention-to-treat set (defined as positive Candida cultured and receiving at least one study drug; 239 for ibrexafungerp, 121 for placebo). Compared with placebo, patients receiving ibrexafungerp had a significantly higher proportion of clinical cure (51.0% vs. 25.6%), mycological eradication (55.6% vs. 18.2%), overall response (33.9%, vs. 8.3%) at TOC and complete symptom resolution (74.5% vs. 39.7%, all P < 0.001) at follow-up. Subgroup analysis of clinical cure indicated that patients with C. albicans could benefit from ibrexafungerp over placebo. A similar benefit trend was also observed in those with non-albicans Candida by post-hoc analysis. Further analyses revealed similar efficacy of ibrexafungerp between patients with fluconazole non-susceptible C. albicans and fluconazole susceptible C. albicans regarding clinical cure and mycological eradication. Ibrexafungerp was generally well tolerated. Adverse events were primarily gastrointestinal and were mainly mild in severity. CONCLUSIONS: As a first-in-class antifungal agent, ibrexafungerp demonstrated promising efficacy and favorable safety for VVC treatment in Chinese patients. CHINADRUGTRIALS.ORG. CN REGISTRY NUMBER: CTR20220918.

Gender Differences in the Prevalence and Clinical Correlates of Metabolic Syndrome in First-Episode and Drug-Naïve Patients With Major Depressive Disorder.

OBJECTIVE: Major depressive disorder (MDD) is a severe psychiatric symptom worldwide, and the coexistence of MDD with metabolic syndrome (MetS) is common in clinical practice. However, gender differences in comorbid MetS in first-episode and drug-naïve (FEDN) MDD patients have not been reported. Here, we explored potential gender differences in the prevalence and clinical correlates of comorbid MetS in FEDN MDD patients. METHODS: A cross-sectional study of 1718 FEDN MDD patients was conducted. Demographic and clinical data were collected. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale, and Positive and Negative Syndrome Scale positive subscale were used to evaluate depression, anxiety, and psychotic symptoms, respectively. RESULTS: The prevalence of MetS was 1.645-fold higher in female MDD patients (38.50%) than in male patients (26.53%). Patients with MetS had higher HAMD score, Hamilton Anxiety Scale score, and Positive and Negative Syndrome Scale positive subscale score than patients without MetS (p values < .001). Furthermore, suicide attempts (male: odds ratio [OR] = 1.706, p = .034; female: OR = 1.639, p = .004) and HAMD score (male: OR = 1.251, p < .001; female: OR = 1.148, p < .001) were independently associated with MetS in male and female patients, whereas age of onset was independently associated with MetS only in female patients (OR = 1.744, p = .047). CONCLUSIONS: Our findings suggest significant gender differences in the prevalence and clinical correlates of comorbid MetS in FEDN MDD patients. Clinical variables (suicide attempts and HAMD scores) may be independently associated with MetS in MDD patients.

TIN2-mediated reduction of mitophagy induces RPE senescence under high glucose.

The telomere-associated protein TIN2 localizes to both telomeres and mitochondria. Nevertheless, the impact of TIN2 on retinal pigment epithelial (RPE) cells in diabetic retinopathy (DR) remains unclear. This research aims to examine the role of TIN2 in the senescence of RPE and its potential as a therapeutic target. Western blotting and immunofluorescence staining were utilized to identify TIN2 expression and mitophagy. RT-qPCR was employed to identify senescent associated secretory phenotype (SASP) in ARPE-19 cells infected with TIN2 overexpression. To examine mitochondria and the cellular senescence of RPE, TEM, SA-ß-gal staining, and cell cycle analysis were used. The impact of TIN2 was examined using OCT and immunohistochemistry in mice. DHE staining and ZO-1 immunofluorescence were applied to detect RPE oxidative stress and tight junctions. Our research revealed that increased mitochondria-localized TIN2 aggravated the cellular senescence of RPE cells both in vivo and in vitro under hyperglycemia. TIN2 overexpression stimulated the mTOR signaling pathway in ARPE-19 cells and exacerbated the inhibition of mitophagy levels under high glucose, which can be remedied through the mTOR inhibitor, rapamycin. Knockdown of TIN2 significantly reduced senescence and mitochondrial oxidative stress in ARPE-19 cells under high glucose and restored retinal thickness and RPE cell tight junctions in DR mice. Our study indicates that increased mitochondria-localized TIN2 induced cellular senescence in RPE via compromised mitophagy and activated mTOR signaling. These results propose that targeting TIN2 could potentially serve as a therapeutic strategy in the treatment of DR.

Room-temperature fabrication of fluorinated covalent organic polymer @ Attapulgite composite for in-syringe membrane solid-phase extraction and analysis of domoic acid in aquatic products.

A novel fluorinated covalent organic polymer @ attapulgite composite (F-COP@ATP) was prepared at room temperature for in-syringe membrane solid-phase extraction (SM-SPE) of domoic acid (DA) in aquatic products. Natural ore ATP has the advantages of low cost, good mechanical strength and abundant hydroxyl group on its surface, and in-situ modified F-COP layer can provide abundant adsorption sites. F-COP@ATP combining the advantages of F-COP and ATP, becomes an ideal adsorbent for DA extracting. Moreover, a high-throughput sample preparation strategy was carried out by using the F-COP@ATP membrane as syringe filter and assembling syringes with a ten-channel injection pump. In addition, the experimental factors were optimized, such as pH of extract, amount of adsorbent, velocity of extraction and desorption, type and volume of desorption solvent. The DA analytical method was established by SM-SPE-HPLC/tandem mass spectrometry. The method had a wide linear range with low limit of detection (0.344 ng/kg) and low limit of quantification (1.14 ng/kg). F-COP@ATP membrane can be reused more than five times. The method realized the analysis of DA in scallop and razor clam samples, which shows its application prospect in practical analysis. This study provided an efficient, low-energy and mild idea for preparing other reusable natural mineral ATP-based composite materials for separation and enrichment, which reduces the experimental cost and is closer to environmental protection and green chemistry to a certain extent.

Allosteric regulation of nitrate transporter NRT via the signaling protein PII.

Coordinated carbon and nitrogen metabolism is crucial for bacteria living in the fluctuating environments. Intracellular carbon and nitrogen homeostasis is maintained by a sophisticated network, in which the widespread signaling protein PII acts as a major regulatory hub. In cyanobacteria, PII was proposed to regulate the nitrate uptake by an ABC (ATP-binding cassette)-type nitrate transporter NrtABCD, in which the nucleotide-binding domain of NrtC is fused with a C-terminal regulatory domain (CRD). Here, we solved three cryoelectron microscopy structures of NrtBCD, bound to nitrate, ATP, and PII, respectively. Structural and biochemical analyses enable us to identify the key residues that form a hydrophobic and a hydrophilic cavity along the substrate translocation channel. The core structure of PII, but not the canonical T-loop, binds to NrtC and stabilizes the CRD, making it visible in the complex structure, narrows the substrate translocation channel in NrtB, and ultimately locks NrtBCD at an inhibited inward-facing conformation. Based on these results and previous reports, we propose a putative transport cycle driven by NrtABCD, which is allosterically inhibited by PII in response to the cellular level of 2-oxoglutarate. Our findings provide a distinct regulatory mechanism of ABC transporter via asymmetrically binding to a signaling protein.

Distinct transcriptomes and autocrine cytokines underpin maturation and survival of antibody-secreting cells in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple autoantibody types, some of which are produced by long-lived plasma cells (LLPC). Active SLE generates increased circulating antibody-secreting cells (ASC). Here, we examine the phenotypic, molecular, structural, and functional features of ASC in SLE. Relative to post-vaccination ASC in healthy controls, circulating blood ASC from patients with active SLE are enriched with newly generated mature CD19-CD138+ ASC, similar to bone marrow LLPC. ASC from patients with SLE displayed morphological features of premature maturation and a transcriptome epigenetically initiated in SLE B cells. ASC from patients with SLE exhibited elevated protein levels of CXCR4, CXCR3 and CD138, along with molecular programs that promote survival. Furthermore, they demonstrate autocrine production of APRIL and IL-10, which contributed to their prolonged in vitro survival. Our work provides insight into the mechanisms of generation, expansion, maturation and survival of SLE ASC.

A prognostic model for SARS-CoV-2 breakthrough infection: Analyzing a prospective cellular immunity cohort.

BACKGROUND: Following the COVID-19 pandemic, studies have identified several prevalent characteristics, especially related to lymphocyte subsets. However, limited research is available on the focus of this study, namely, the specific memory cell subsets among individuals who received COVID-19 vaccine boosters and subsequently experienced a SARS-CoV-2 breakthrough infection. METHODS: Flow cytometry (FCM) was employed to investigate the early and longitudinal pattern changes of cellular immunity in patients with SARS-CoV-2 breakthrough infections following COVID-19 vaccine boosters. XGBoost (a machine learning algorithm) was employed to analyze cellular immunity prior to SARS-CoV-2 breakthrough, aiming to establish a prognostic model for SARS-CoV-2 breakthrough infections. RESULTS: Following SARS-CoV-2 breakthrough infection, naïve T cells and TEMRA subsets increased while the percentage of TCM and TEM cells decreased. Naïve and non-switched memory B cells increased while switched and double-negative memory B cells decreased. The XGBoost model achieved an area under the curve (AUC) of 0.78, with an accuracy rate of 81.8 %, a sensitivity of 75 %, and specificity of 85.7 %. TNF-α, CD27-CD19+cells, and TEMRA subsets were identified as high predictors. An increase in TNF-α, cTfh, double-negative memory B cells, IL-6, IL-10, and IFN-γ prior to SARS-CoV-2 infection was associated with enduring clinical symptoms; conversely, an increase in CD3+ T cells, CD4+ T cells, and IL-2 was associated with clinical with non-enduring clinical symptoms. CONCLUSION: SARS-CoV-2 breakthrough infection leads to disturbances in cellular immunity. Assessing cellular immunity prior to breakthrough infection serves as a valuable prognostic tool for SARS-CoV-2 infection, which facilitates clinical decision-making.

Fluctuating light induces a significant photoinhibition of photosystem I in maize.

In nature, light intensity usually fluctuates and a sudden shade-sun transition can induce photodamage to photosystem I (PSI) in many angiosperms. Photosynthetic regulation in fluctuating light (FL) has been studied extensively in C3 plants; however, little is known about how C4 plants cope FL to prevent PSI photoinhibition. We here compared photosynthetic responses to FL between maize (Zea mays, C4) and tomato (Solanum lycopersicum, C3) grown under full sunlight. Maize leaves had significantly higher cyclic electron flow (CEF) activity and lower photorespiration activity than tomato. Upon a sudden shade-sun transition, maize showed a significant stronger transient PSI over-reduction than tomato, resulting in a significant greater PSI photoinhibition in maize after FL treatment. During the first seconds upon shade-sun transition, CEF was stimulated in maize at a much higher extent than tomato, favoring the rapid formation of trans-thylakoid proton gradient (ΔpH), which was helped by a transient down-regulation of chloroplast ATP synthase activity. Therefore, modulation of ΔpH by regulation of CEF and chloroplast ATP synthase adjusted PSI redox state at donor side, which partially compensated for the deficiency of photorespiration. We propose that C4 plants use different photosynthetic strategies for coping with FL as compared with C3 plants.

[Research progress of artificial intelligence technology in early diagnosis of sepsis].

Sepsis is caused by infection, which can ultimately lead to multiple organ dysfunction and even life-threatening. Early recognition and early treatment can significantly improve the prognosis of sepsis patients. However, the effect of using a single biomarker for early diagnosis of sepsis is still not ideal. In recent years, researchers have turned their attention to artificial intelligence technology for early diagnosis of sepsis. This paper briefly introduces the advantages and disadvantages of sepsis related inflammatory indicators, biomarkers, and scoring systems of disease severity for early identification of sepsis, and focuses on the research progress and limitations of artificial intelligence technology for early diagnosis of sepsis, aiming to seek new methods and ideas for early diagnosis of sepsis.

PFKFB3 in neovascular eye disease: unraveling mechanisms and exploring therapeutic strategies.

BACKGROUND: Neovascular eye disease is characterized by pathological neovascularization, with clinical manifestations such as intraocular exudation, bleeding, and scar formation, ultimately leading to blindness in millions of individuals worldwide. Pathologic ocular angiogenesis often occurs in common fundus diseases including proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (VEGF) targets the core pathology of ocular angiogenesis. MAIN BODY: In recent years, therapies targeting metabolism to prevent angiogenesis have also rapidly developed, offering assistance to patients with a poor prognosis while receiving anti-VEGF therapy and reducing the side effects associated with long-term VEGF usage. Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme in targeted metabolism, has been shown to have great potential, with antiangiogenic effects and multiple protective effects in the treatment of neovascular eye disease. In this review, we summarize the mechanisms of common types of neovascular eye diseases; discuss the protective effect and potential mechanism of targeting PFKFB3, including the related inhibitors of PFKFB3; and look forward to the future exploration directions and therapeutic prospects of PFKFB3 in neovascular eye disease. CONCLUSION: Neovascular eye disease, the most common and severely debilitating retinal disease, is largely incurable, necessitating the exploration of new treatment methods. PFKFB3 has been shown to possess various potential protective mechanisms in treating neovascular eye disease. With the development of several drugs targeting PFKFB3 and their gradual entry into clinical research, targeting PFKFB3-mediated glycolysis has emerged as a promising therapeutic approach for the future of neovascular eye disease.

Natural Sweetener Glycyrrhetinic Acid Monoglucuronide Improves Glucose Homeostasis in Healthy Mice.

Noncaloric or low-caloric sweeteners have become popular worldwide, although debates persist regarding their impact on health. To investigate whether the sweeteners are favorable for glucose homeostasis, our study assessed the effects of glycyrrhetinic acid monoglucuronide (GAMG) and several commonly used sweeteners [glycyrrhetinic acid (GA), stevioside, erythritol, sucralose, and aspartame] on glycometabolism and elucidated the underlying mechanisms. The C57BL/6J male mice were exposed to different sweeteners for 10 weeks, and our results showed that GAMG significantly reduced fasting blood glucose (FBG) levels (FBG-control: 3.81 ± 0.42 mmol/L; FBG-GAMG: 3.37 ± 0.38 mmol/L; p < 0.05) and the blood glucose levels 15 and 30 min after sucrose or maltose loading (p < 0.05). Furthermore, it improved glucose tolerance (p = 0.028) and enhanced insulin sensitivity (p = 0.044), while the other sweeteners had negligible or adverse effects on glucose homeostasis. Subsequent experiments showed that GAMG inhibited α-glucosidases potently (IC50 = 0.879 mg·mL-1), increased three SCFA-producing bacteria and SCFAs levels (p < 0.05), and promoted the gene expression of SCFA receptor GPR43 (p = 0.018). These results suggest that GAMG may regulate blood glucose by inhibiting α-glucosidases and modulating gut microbial SCFAs. Our findings prove that GAMG, beneficial to blood glucose regulation, is a promising natural sweetener for future utilization.

LAIR1-mediated resistance of hepatocellular carcinoma cells to T cells through a GSK-3ß/ß-catenin/MYC/PD-L1 pathway.

BACKGROUND: An increasing number of studies have reported the involvement of oncogenes in the regulation of the immune system. LAIR1 is an immunosuppressive molecule and its role in immune-related diseases has been mainly reported. To date, it is unclear whether LAIR1 in tumor cells is involved in immune regulation. Therefore, the aim of this study was to investigate the role of LAIR1 in the immune microenvironment of hepatocellular carcinoma (HCC) to seek the novel therapeutic discoveries. METHODS: Tumor Immune Dysfunction and Exclusion database was used to predict the response of LAIR1 expression to immune checkpoint blockade. CD8+ T cells were co-cultured with HCC cells, and the killing efficiency of leukocytes on HCC cells was detected by flow cytometry. Flow cytometry was also used to detect the expression of inhibitory receptors. In addition, Western blot, immunofluorescence, and nucleus/cytoplasm fractionation experiments were performed to explore the molecular mechanisms by which LAIR1 created a suppressive tumor microenvironment. RESULTS: LAIR1 expression in HCC was associated with worse immune prognosis and T-cell dysfunction. HCC cells overexpressing LAIR1 co-cultured with CD8+ T cells induced exhaustion of latter. Mechanism studies indicated that LAIR1 in HCC cells up-regulated the phosphorylation of ß-catenin by inducing the phosphorylation of GSK-3ß, leading to the impairment of the expression and the nuclear localization signal of ß-catenin. Low ß-catenin expression and nuclear localization signal inhibited MYC-mediated PD-L1 expression. Therefore, PD-L1 up-regulated by LAIR1 caused the exhaustion of infiltrating CD8+ T cells in HCC, which aggravated the malignant progression of HCC. CONCLUSION: LAIR1 increased PD-L1 expression through the GSK-3ß/ß-catenin/MYC/PD-L1 pathway and promoted immune evasion of HCC cells. Targeted inhibition of LAIR1 helped to enhance the immune killing effect of CD8+ T cells in HCC.

Effective disinfecting of negative pressure pipelines of DCUs reduces the risk of cross infection in dental care.

Objectives: Microbial contamination of various accessory parts of the dental chair units (DCUs) is an essential source of cross infection, while the accessories of the crucial suction function are usually overlooked. In this study, we aim to find an effective disinfectant and a cost-effective method to remove bacterioplankton and bacterial biofilm deposited in the negative pressure suction pipelines to control cross infection during dental treatment. Methods: Double-chain quaternary ammonium salt disinfectant (Orotol Plus®), 3% hydrogen peroxide solution plus multi-enzyme cleaning agent and chlorine disinfectant are used to clean and disinfect the negative pressure pipelines of DCUs. Microbiological examinations, air condition detection, corrosion tests and gene sequencing are performed. Results: Little bacteria grow in the pipelines disinfected with double-chain quaternary ammonium salt disinfectants, destruction of biofilms in these pipelines appears, and multi-resistant bacteria cannot be detected. Minimal damage to metal sheets and fittings is caused by double-chain quaternary ammonium salt disinfectants. Conclusion: Double-chain quaternary ammonium salt disinfectant has excellent bactericidal ability and anti-biofilm effect, and it is less corrosive to the fittings of the pipelines. Thus, the double-chain quaternary ammonium salt disinfectant is a potential novel disinfectant for negative pressure suction pipelines of DCUs to control cross infection during dental treatment. Clinical significance: It is essential to add all these data to our dental practice to control cross infection with a broader landscape.

Prevalence and risk factors for subclinical hypothyroidism in older patients with major depressive disorder.

BACKGROUND: Subclinical hypothyroidism (SCH) is highly correlated with major depressive disorder (MDD). However, the prevalence and risk factors for SCH in older patients with MDD have rarely been reported in China. METHODS: This cross-sectional study included 266 older MDD patients with SCH was performed. Clinical and anthropometric, biochemical, and thyroid function data were collected. Depression, anxiety, and psychotic symptoms were assessed using the Hamilton Depression Scale, the Hamilton Anxiety Scale, and the Positive and Negative Syndrome Scale positive subscale, respectively. RESULTS: Among older patients with MDD, the prevalence of SCH was 64.7% (172/266). Compared to patients without SCH, older MDD patients with SCH had a longer disease course and higher TSH, A-TG, A-TPO, HDL-C, LDL-C, TC, FPG, and systolic pressure levels (all P ≤ 0.002). Furthermore, disease progression (OR 1.082, 95% CI 1.020-1.147, P = 0.009), A-TG (OR 1.005, 95% CI 1.001-1.009, P = 0.017), TC (OR 2.024, 95% CI 1.213-3.377, P = 0.007), FPG (OR 2.916, 95% CI 1.637-5.194, P < 0.001), systolic pressure (OR 1.053, 95% CI 1.008-1.100, P = 0.022) were independently associated with SCH, in older patients with MDD. CONCLUSIONS: Our findings suggest a high prevalence of SCH in older patients with MDD. Several demographic and clinical variables were independently associated with SCH in older patients with MDD.