Engineering a NanoBiT biosensor for detecting angiotensin-converting enzyme-2 (hACE2) interaction with SARS-CoV-2 spike protein and screening the inhibitors to block hACE2 and spike interaction.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated by its trimeric surface spike protein, which binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. This critical interaction facilitates viral entry and is a primary target for therapeutic intervention against COVID-19. However, it is difficult to fully optimize viral infection using existing protein-protein interaction methods. Herein, we introduce a nano-luciferase binary technology (NanoBiT)-based pseudoviral sensor designed to stimulate the dynamics of viral infection in both living cells and animals. Infection progression can be dynamically visualized via a rapid increase in luminescence within 3 h using an in vivo imaging system (IVIS). Inhibition of viral infection by baicalein and baicalin was evaluated using a NanoBiT-based pseudoviral sensor. These results indicate that the inhibitory efficacy of baicalein was strengthened by targeting the spike protein, whereas baicalin targeted the hACE2 protein. Additionally, under optimized conditions, baicalein and baicalin provided a synergistic combination to inhibit pseudoviral infection. Live bioluminescence imaging was used to evaluate the in vivo effects of baicalein and baicalin treatment on LgBiT-hACE2 mice infected with the BA.2-SmBiT spike pseudovirus. This innovative bioluminescent system functions as a sensitive and early-stage quantitative viral transduction in vitro and in vivo. This platform provides novel opportunities for studying the molecular biology of animal models.

Orthogonal Electrochemical Stability of Bulk and Surface in Lead Halide Perovskite Thin Films and Nanocrystals.

Lead halide perovskites have attracted significant attention for their wide-ranging applications in optoelectronic devices. A ubiquitous element in these applications is that charging of the perovskite is involved, which can trigger electrochemical degradation reactions. Understanding the underlying factors governing these degradation processes is crucial for improving the stability of perovskite-based devices. For bulk semiconductors, the electrochemical decomposition potentials depend on the stabilization of atoms in the lattice-a parameter linked to the material's solubility. For perovskite nanocrystals (NCs), electrochemical surface reactions are strongly influenced by the binding equilibrium of passivating ligands. Here, we report a spectro-electrochemical study on CsPbBr3 NCs and bulk thin films in contact with various electrolytes, aimed at understanding the factors that control cathodic degradation. These measurements reveal that the cathodic decomposition of NCs is primarily determined by the solubility of surface ligands, with diminished cathodic degradation for NCs in high-polarity electrolyte solvents where ligand solubilities are lower. However, the solubility of the surface ligands and bulk lattice of NCs are orthogonal, such that no electrolyte could be identified where both the surface and bulk are stabilized against cathodic decomposition. This poses inherent challenges for electrochemical applications: (i) The electrochemical stability window of CsPbBr3 NCs is constrained by the reduction potential of dissolved Pb2+ complexes, and (ii) cathodic decomposition occurs well before the conduction band can be populated with electrons. Our findings provide insights to enhance the electrochemical stability of perovskite thin films and NCs, emphasizing the importance of a combined selection of surface passivation and electrolyte.

Complementary Chinese Herbal Medicine Treatment is Associated with a Reduction of Surgical Rate in Patients with Dysfunctional Uterine Bleeding: A Propensity-Score Matched Cohort Study.

Background: Many patients with dysfunctional uterine bleeding (DUB) seek traditional medicine consultations. This study intended to investigate the association of complementary Chinese herbal medicine (CHM) with the surgery rate in patients with DUB in Taiwan. Methods: We enrolled 43,027 patients with newly diagnosed DUB (ICD-9-CM codes 626.8) from the National Health Insurance Research Database in Taiwan during the period of 1997 to 2010. Among them, 38,324 were CHM users, and 4703 did not receive CHM treatment. After performing a 1:1 propensity-score match based on patients' age (per 5 years), comorbidities, conventional drugs, childbirth status, duration from the diagnosis year of DUB and index year, there were an equal number (n=4642) of patients in the CHM cohort and non-CHM cohort. The outcome measurement was the comparison of incidences of surgical events, including hysterectomy and endometrial ablation, in the two cohorts before the end of 2013. Results: CHM users had a lower incidence of surgery than non-CHM users (adjusted HR 0.27, 95% CI: 0.22-0.33). The cumulative incidence of surgery was significantly lower in the CHM cohort during the follow-up period (Log rank test, p < 0.001). A total of 146 patients in the CHM cohort (4.99 per 1000 person-years) and 485 patients in the non-CHM cohort (20.19 per 1000 person-years) received surgery (adjusted HR 0.27, 95% CI: 0.22-0.33). CHM also reduced the risk of surgery in DUB patients with or without comorbidities. Regardless of childbirth status or whether patients took NSAIDs, tranexamic acid or progesterone, fewer patients in the CHM cohort underwent surgery than in the non-CHM cohort. The most commonly prescribed single herb and formula were Yi-Mu-Cao (Herba Leonuri) and Jia-Wei-Xiao-Yao-San, respectively. Conclusion: The real-world data revealed that CHM is associated with a reduced surgery rate in DUB patients. This information may be provided for further clinical investigations and policy-making.

Failure patterns and individualized treatment plans of reirradiation for inoperable locally recurrent nasopharyngeal carcinoma.

Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.

Antihyperlipidemic drugs mitigate the elevated incidence of peptic ulcer disease caused by Hyperlipidemia: A cohort study.

BACKGROUND: Several risk factors for peptic ulcer disease (PUD) have been identified; however, the recurrence rates of PUD are still high even with standard ulcer treatments. A high cholesterol level has been proposed as a risk factor for PUD, but clinical evidence remains limited. Therefore, this database study investigated whether hyperlipidemia increases PUD risk and whether antihyperlipidemic drugs reduce this risk. METHODS: A long-term cohort design was adopted, and Taiwan's National Health Insurance Research Database was used to enroll patients diagnosed as having hyperlipidemia between 2000 and 2016. Patients without hyperlipidemia were randomly matched based on variables such as age and gender to establish a comparison cohort at a 1:1 ratio. Another cohort study was conducted to determine whether antihyperlipidemic drugs or red yeast rice prescriptions (LipoCol Forte®) can reduce the incidence of PUD in patients with hyperlipidemia. RESULTS: The overall incidence of PUD was 1.48 times higher in the hyperlipidemia cohort (203,235 patients) than in the nonhyperlipidemia cohort (adjusted hazard ratio, 1.48; 95% CI, 1.46-1.50; p < 0.001). Among the patients with hyperlipidemia, those who used antihyperlipidemic drugs with or without red yeast rice prescriptions exhibited a lower risk of developing PUD relative to those who did not use them; the adjusted hazard ratios were 0.33 (95% CI, 0.21-0.52) and 0.81 (95% CI, 0.78-0.84), respectively. When the cumulative exposure to antihyperlipidemic drugs and red yeast rice prescriptions increased, the risk of developing PUD showed a decreasing trend, which was statistically significant for antihyperlipidemic drugs but not for red yeast rice. CONCLUSION: Hyperlipidemia is associated with a higher risk of PUD, which can be reduced through antihyperlipidemic drugs with or without red yeast rice prescriptions administration.

Mycoplasma pneumoniae infection outbreak in Guangzhou, China after COVID-19 pandemic.

BACKGROUNDS: Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Throat swab samples were obtained from 5405 hospitalized patients with symptoms of acute respiratory infections to detect M. pneumoniae. Differences in epidemiological and clinical characteristics of M. pneumoniae: infections were investigated during 2020-2022 and after COVID-19 pandemic (2023). RESULTS: M. pneumoniae were detected in 849 (15.6%, 849/5405) patients. The highest annual positive rate was 29.4% (754/2570) in 2023, followed by 5.3% (72/1367) in 2022, 1.2% (12/1015) in 2021, and 2.0% (11/553) in 2020, with significantly increasing annual prevalence from 2020 to 2023. M. pneumoniae incidence peaked between July and December post-COVID-19 pandemic in 2023, with the highest monthly positive rate (56.4%, 165/293). Clinical characteristics and outcomes of patients with M. pneumoniae did not vary between periods during and after COVID-19 pandemic except that patients with M. pneumoniae post-COVID-19 pandemic were more likely to develop fever. Patients with severe M. pneumoniae pneumonia (SMPP) were more likely to develop respiratory complications, myocardial damage, and gastrointestinal dysfunction than those with non-SMPP. Patients with SMPP had lower lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP. Bronchoalveolar lavage fluid specimens from infected patients were obtained to identify macrolide resistance mutations. Macrolide-resistant M. pneumoniae (MRMP) proportion in 2023 was 91.1% (215/236). CONCLUSION: Outbreaks of M. pneumoniae: occurred in Guangzhou, China in 2023 upon Non-pharmaceutical interventions easing. Despite the increasing incidence of M. pneumoniae, the disease severity remained similar during and after the COVID-19 pandemic.

Evaluating the risk of new-onset glaucoma in chronic kidney disease patients: a nationwide cohort study.

BACKGROUND: A better understanding of the association between chronic kidney disease (CKD) and glaucoma is required to optimize clinical outcomes. Therefore, this study aimed to investigate the association of chronic kidney disease (CKD) with new diagnoses of glaucoma over time from January 2009 to December 2019. METHOD: This retrospective propensity-matched cohort study utilizing Taiwanese electronic health records examined the incidence of newly diagnosed glaucoma in patients with and without chronic kidney disease (CKD). The exposure variable was the diagnosis of CKD, identified through diagnostic codes. The primary outcome was the incidence of new-onset glaucoma. Subgroup analyses on glaucoma risk included age, gender, comorbidities, glaucoma subtypes, and dialysis status. Statistical analyses included Kaplan-Meier analysis, Cox proportional hazards models, and Poisson regression models, with the associated hazard ratios and confidence intervals reported. RESULTS: Seven hundred twenty-three thousand two hundred sixteen patients with CKD (42.3% female; mean [SD] age at index, 66.3 [15.6] years) and 723,216 patients without CKD (42.3% female; mean [SD] age at index, 66.3 [15.7]) were recruited. We showed a significantly increased risk of glaucoma irrespective of subtypes in CKD patients compared to those without CKD (HR: 1.29 [CI: 1.26-1.32], p < 0.001). Kaplan-Meier curves revealed a significantly increased glaucoma risk in both the dialytic subtype and non-dialytic CKD patients when compared to their non-CKD counterparts (p < 0.001). We also showed that all genders (aHR 1.17 [CI: 1.13-1.21] for females vs. aHR 1.39 [CI:1.35-1.43] for males), all ages (< = 49: aHR 1.49 [CI: 1.37-1.62]; 50-59: aHR 1.48 [CI: 1.40-1.56]; 60-69: aHR 1.30 [CI: 1.25-1.6]; 70-79: aHR 1.21 [CI: 1.17-1.26]; > 80: aHR 1.29 [CI: 1.21-1.37]); all income brackets and all urbanization status were associated with significantly increased risk of glaucoma from among the CKD cohort when compared to their respective non-CKD cohort (p < 0.001). CONCLUSIONS: Our cohort study spanning 12 years showed an elevated glaucoma risk following a CKD diagnosis compared to a frequency-matched non-CKD cohort. Our findings have relevance for the clinical practice of at-risk CKD patients. TRIAL REGISTRATION: Due to the retrospective nature of the study, no registration was necessary.

Short-Term Effects of an eHealth Care Experiential Learning Program Among Patients With Type 2 Diabetes: Randomized Controlled Trial.

BACKGROUND: Type 2 diabetes is a chronic disease with a significant medical burden. eHealth care integrates medicine and technology to enhance the outcomes of such patients; however, adequate eHealth literacy (eHL) is necessary for that to happen. Fostering eHL is crucial for patients with diabetes to engage with eHealth care and receive quality care and timely support. Experiential learning theory can enhance patients' eHL and skills to use eHealth care technology in their daily care. OBJECTIVE: This study explored the effectiveness of an eHealth care experiential learning program in improving eHL, patient health engagement, and eHealth care use status among patients with type 2 diabetes in 3 months. METHODS: In this randomized controlled trial, patients under case management services from various clinics in Taiwan were randomly assigned to either the intervention group receiving the 6-session eHealth care experiential learning program or the control group receiving the usual care. Data were collected using structured questionnaires at 3 time points: pretest, postintervention, and 3 months after the intervention. Descriptive data were presented using frequency distribution, percentage, mean, and SD. The outcomes were analyzed using a generalized estimating equation method by intention-to-treat analysis. RESULTS: A total of 92 participants (46 in each group) were recruited in this study. Of these, 86 completed the course and follow-up evaluations with a mean age of 62.38 (SD 12.91) years. After completing the intervention, the intervention group had significantly higher posttest scores in eHL (ß=19.94, SE 3.52; P<.001), patient health engagement (ß=.28, SE 0.13; P=.04), and eHealth use (ß=3.96, SE 0.42; P<.001) than the control group. Furthermore, the intervention group maintained these significant improvements in eHL (ß=18.19, SE 3.82; P<.001) and eHealth use (ß=3.87, SE 0.49; P<.001) after 3 months. CONCLUSIONS: Participating in the eHealth care experiential learning program resulted in significant improvements in eHL, patient health engagement, and eHealth use among patients with type 2 diabetes. Our interventional program can inform future clinical practice and policies to strengthen self-management skills and facilitate the use of health technology in caring for patients with chronic diseases. TRIAL REGISTRATION: ClinicalTrials.gov NCT05180604; https://clinicaltrials.gov/ct2/show/NCT05180604.

Treatment with autophagic inhibitors enhances oligonol­induced apoptotic effects in nasopharyngeal carcinoma cells.

Although the combination of chemotherapy and radiotherapy has increased the survival rate of patients with nasopharyngeal carcinoma (NPC), certain patients do not respond well to the treatment and have a poor prognosis. Therefore, novel therapeutic drugs and strategies to improve prognosis of patients with NPC are required. As certain plant extracts can suppress the viability of cancer cells, the present study investigated whether oligonol, a polyphenolic compound primarily found in lychee fruit, exerts anticancer activities in NPC cells. MTT, ELISA and immunoblotting were performed to investigate cell survival, cytokeratin-18 fragment release, and the expression of apoptosis and autophagy markers, respectively. Oligonol decreased the viability of NPC-TW01 and NPC/HK1NPC cell lines. Oligonol increased the protein expression of several apoptosis markers, including cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment. Moreover, it also increased expression of autophagy markers Beclin 1 and LC3-II, as well as LC3-II/LC3-I ratio in both NPC cell lines. Furthermore, treatment with autophagy inhibitors 3-methyladenine or LY294002 significantly increased oligonol-induced viability inhibition in NPC-TW01 cells. Combined treatment of oligonol + LY294002 reduced LC3-II expression and the LC3II/LC3I ratio while increasing cleaved caspase-8 and -3, cleaved PARP and cytokeratin 18 fragment expression in NPC-TW01 cells. These findings indicated autophagy inhibitors could enhance viability inhibition and apoptotic effects induced by oligonol in NPC cells.

van der Waals-bonded graphene clusters enhance thermal conductivity of phase-change materials for advanced thermal energy management.

Organic phase-change materials possess immense application potential, but their low thermal conductivity (≤0.5 W m-1 K-1) severely limits the thermal energy charge/discharge rate, impeding their practical implementation in the field of advanced energy. While incorporating thermally conductive fillers into the phase-change matrix can address this issue, achieving a thermal conductivity exceeding 10 W m-1 K-1 at a filler content below 30 vol% remains challenging, attributed to the absence of a well-designed filler interface and structure. Herein, a strategy for developing planar graphene clusters and subsequently integrating them with phase-change microcapsules to fabricate composites using compression molding was demonstrated. The proposed graphene clusters are formed by closely aligned and overlapping graphene sheets that bond together through van der Waals forces, resulting in a significant decrease in junction thermal resistance within the composites. Combining this interface design with compression-induced construction of a highly oriented structure, the composites achieved a remarkable thermal conductivity of 103 W m-1 K-1 with ≈29 vol% filler addition, enhancing the thermal energy charge/discharge rate by over two orders of magnitude. Furthermore, we demonstrated that the composites possess the essential enthalpy values, competent strength, and ease of shaping, making them applicable across various domains of thermal energy management.

Do low skeletal muscle bulk and disturbed body fat mass impact tumor recurrence in stage I/II HCC undergoing surgery? An observational cohort study.

INTRODUCTION: The influence of deranged body composition on stage I/II HCC after surgery remains undetermined. The current study aimed to investigate the impact of low skeletal muscle bulk and disturbed body fat mass on the recurrence outcome of stage I/II HCC patients undergoing liver resection. The associated metabolomic alterations were also assessed. METHODS: From 2012 to 2021, stage I and II HCC patients who underwent liver resection at our institute were retrospectively reviewed. Their preoperative body composition including skeletal muscle mass and body fat volume was measured by computed tomography (CT). The recurrence outcome was recorded and analyzed. The preoperative serum was collected and subjected to metabolomic analysis. RESULTS: A total of 450 stage I and II HCC patients were included in the current study. Among them, 76% were male and around 60% had HBV infection. After stratified by normal cutoff values obtained from a healthy cohort, 6.4% of stage I/II HCC patients were found to have a low psoas muscle index (PMI), 17.8% a high subcutaneous adipose tissue (SAT) index, and 27.8% a high visceral adipose tissue (VAT) index. Cox regression multivariate analysis further demonstrated that low PMI and high SAT index were independent prognostic factors for time-to-recurrence (TTR) after surgery. Metabolomic analysis discovered that free fatty acid ß-oxidation was enhanced in with low PMI or high SAT index. CONCLUSION: The current study demonstrated that reduced psoas muscle mass may impair while elevated SAT may prolong the TTR of stage I/II HCC patients undergoing liver resections. VAT, on the other hand, was not associated with recurrence outcome after surgery. Further studies are warranted to validate our findings.

Bidirectional causal associations between aging and major mental disorders: A population-based study using the two-sample mendelian randomization method from the UK biobank (AM-SRNMA 002).

AIMS: While observational studies have suggested associations linking aging and mental disorders, the question of causality has remained unclear. This study aimed to explore the causal relationship between aging level and major mental disorders. METHODS: We utilized Two-Sample Mendelian randomization (2SMR) with mental disorders data and aging indicators information from an extensive genome-wide association study (GWAS) database. The GWAS database is a comprehensive resource that compiles genetic association data, encompassing a sample size of over 450,000 individuals. We employed five methods for 2SMR and single nucleotide polymorphisms were chosen as instrumental variables. RESULTS: Our analyses consistently supported a bidirectional causal association between the Frailty Index (FI) and Major Depressive Disorder (MDD). Furthermore, our findings indicated potential influences, such as Attention-Deficit/Hyperactivity Disorder (ADHD) and Bipolar Disorder (BD) affecting GrimAge, and Anxiety Disorder (AD) impacting Left Hand Grip Strength (LHGS). In contrast, we observed no significant correlations for other mental disorders on FI, Telomere Length (TL), GrimAge, Appendicular Lean Mass (ALM), and LHGS. In the reverse direction, FI showed a significant impact on the risk of MDD, AD, and ADHD, while LHGS affected the risk of MDD. Importantly, no significant associations were found between other factors and the risk of MDD, BD, AD, Schizophrenia (SZ), and ADHD. CONCLUSIONS: This 2SMR analysis has presented evidence for a bidirectional causal relationship between FI and MDD, while the relationship between ADHD, BD, and GrimAge should be more considered. Our study provides genetic evidence supporting a causal link between aging indicators and several mental illnesses.

Overexpression of CENPU promotes cancer growth and metastasis and is associated with poor survival in patients with nasopharyngeal carcinoma.

Background: Centromere protein U (CENPU) is key for mitosis in the carcinogenesis of cancers. However, the roles of CENPU have not been inspected in nasopharyngeal carcinoma (NPC). Thus, we aimed to explore the functions and mechanisms of CENPU in NPC. Methods: Expression of CENPU was evaluated by real-time quantitative polymerase chain reaction, western blotting and immunohistochemistry. The biological functions of CENPU were evaluated in vitro and in vivo. Gene chip analysis, ingenuity pathway analysis, and coimmunoprecipitation experiments were used to explore the mechanisms of CENPU. Results: CENPU was highly expressed in NPC. High expression of CENPU was associated with advanced tumor, node and metastasis (TNM) stage and poor overall survival. Cox regression analysis demonstrated that CENPU expression was an independent prognostic factor in NPC. Knockdown of CENPU inhibited proliferation and migration in vitro and in vivo. Knockdown of CENPU upregulated dual specificity phosphatase 6 (DUSP6) expression. The expression of CNEPU was inversely correlated with the expression of DUSP6 in NPC tissues. Mechanistic studies confirmed that CENPU increased the activation of the ERK1/2 and p38 signaling pathways by suppressing the expression of DUSP6. Conclusions: CENPU acts as an oncogene in NPC by interacting with DUSP6, and may represent a promising prognostic biomarker for patients with NPC.

Thermosensitive Hydrogels as Targeted and Controlled Drug Delivery Systems: Potential Applications in Transplantation.

Drug delivery in transplantation plays a vital role in promoting graft survival, preventing rejection, managing complications, and contributing to positive patient outcomes. Targeted and controlled drug delivery can minimize systemic effects. Thermosensitive hydrogels, due to their unique sol-gel transition properties triggered by thermo-stimuli, have attracted significant research interest as a potential drug delivery system in transplantation. This review describes the current status, characteristics, and recent applications of thermosensitive hydrogels for drug delivery. Studies aimed at improving allotransplantation outcomes using thermosensitive hydrogels are then elaborated on. Finally, the challenges and opportunities associated with their use are discussed. Understanding the progress of research will serve as a guide for future improvements in their application as a means of targeted and controlled drug delivery in translational therapeutic applications for transplantation.

Colon perforation with severe peritonitis caused by erotic toy insertion and treated using vacuum-assisted closure: A case report.

BACKGROUND: Colorectal foreign bodies are commonly encountered during surgery. They are frequently observed in men 20 to 90 years of age and have bimodal age distribution. Surgical management is necessary for cases of rectal perforation. However, surgical site infections are the most common complications after colorectal surgery. CASE SUMMARY: We discuss a case of rectal perforation in a patient who presented to our hospital 2 d after its occurrence. The perforation occurred as a result of the patient inserting a sex toy in his rectum. Severe peritonitis was attributable to delayed presentation. CONCLUSION: Vacuum-assisted closure was performed to treat the wound, which healed well after therapy. No complications were noted.

Risk Factors and Nomogram Model for Hepatocellular Carcinoma Development in Chronic Hepatitis B Patients with Low-Level Viremia.

Background and aim: Patients with chronic hepatitis B patients (CHB) with low-level viremia (LLV) are not necessarily at low risk of developing hepatocellular carcinoma (HCC). The question of whether CHB patients with LLV require immediate antiviral agent (AVT) or long-term AVT remains controversial. The study aims to investigate the risk of HCC development and the risk factors in CHB patients with LLV and construct a nomogram model predicting the risk of HCC. Methods: We conducted a retrospective cohort study that enrolled 16,895 CHB patients from January 2008 to December 2020. The patients were divided into three groups for comparison: the LLV group, maintained virological response (MVR) group and HBV-DNA>2000 group. The cumulative incidence of progression to HCC was assessed. Cox regression analysis was performed to determine the final risk factors, and a nomogram model was constructed. The 10-fold Cross-Validation method was utilized for internal validation. Results: A total of 408 new cases of HCC occurred during the average follow-up period of 5.78 years. The 3, 5, and 10-year cumulative HCC risks in the LLV group were 3.56%, 4.96%, and 9.51%, respectively. There was a significant difference in the cumulative risk of HCC between the HBV-DNA level > 2000 IU/mL and LLV groups (p = 0.049). Independent risk factors for HCC development in LLV group included male gender, age, presence of cirrhosis, and platelets count. The Area Under the Curve (AUC) values for the 3-year and 5-year prediction from our HCC risk prediction model were 0.75 and 0.76, respectively. Conclusion: Patients with LLV and MVR are still at risk for developing HCC. The nomogram established for CHB patient with LLV, incorporating identified significant risk factors, serves as an effective tool for predicting HCC-free outcomes. This nomogram model provides valuable information for determining appropriate surveillance strategies and prescribing AVT.

The weight of weights: Causal impact of overweight on major depressive disorder and its disparate association with suicide attempts in over 450,000 individuals of European ancestry (AM-SRNMA 003).

AIM: Some studies and societal discussions have suggested a potential link between overweight and a higher risk of mental disorders and suicidal ideation. However, the causal relationships between these factors remain unclear. This study aims to assess the bidirectional causal associations between overweight and mental disorders, including suicidal attempts. METHOD: We conducted a Two-Sample Mendelian Randomization study utilizing data from over 450,000 individuals of European ancestry sourced from a comprehensive Genome-Wide Association Study database. We chose single-nucleotide polymorphisms as instrumental variables. RESULTS: Our analyses consistently supported a unidirectional causal association of overweight with the increased risk of major depressive disorder (MDD, ß = 0.152, se = 0.069, P = 0.027), bipolar affective disorders (BD, ß = 0.197, se = 0.092, P = 0.033), and attention-deficit / hyperactivity disorder (ADHD, ß = 0.308, se = 0.080, P = 1.366 × 10-4). We observed no significant causal relationships for the exposure of overweight to anxiety disorder (AD), manic episode (MA), panic disorder (PD), schizophrenia (SZ), substance use disorder (SUD), autism spectrum disorder (ASD), ever attempted suicide, recent thoughts of suicide or self-harm, and suicide or other intentional self-harm events. CONCLUSION: This study has provided evidence for the causal relationship between overweight and MDD, BD, ADHD, with no observed relationship between overweight and AD, MA, PD, SZ, SUD, ASD, ever attempted suicide, recent thoughts of suicide or self-harm, and suicide or other intentional self-harm events.

Prognostic value of CMTM6 protein in hepatocellular carcinoma involving the regulation of the immune microenvironment.

There have been notable irregularities in CMTM6 expression observed in hepatocellular carcinoma (HCC), with an evident correlation between CMTM6 dysregulation and patient prognosis. The cell cycle progression came to a halt at the G2/M phase. In-depth RNA-sequencing analysis of CMTM6 knockdown Hep3B cells revealed that the most prominent effect of CMTM6 perturbation was on the expression of CXCL8, a chemokine involved in immune responses, particularly through the interleukin-17F (IL-17F) signaling pathway. By carefully examining the RNA-sequencing data obtained from CMTM6 knockdown Hep3B cells and cross-referencing it with the TCGA-LIHC database, we were able to discern that CMTM6 and programmed death-ligand 1 (PD-L1) collaboratively partake in immune regulation within T cells. Furthermore, CMTM6 exerted an influential role in modulating the infiltration of CD4+ and CD8+ T cells in the HCC microenvironment, thereby impacting the overall immune response. Our investigation found that HCC cases characterized by an elevated co-expression of CMTM6 and PD-L1, along with augmented CD4+ T cell infiltration, demonstrated comparatively longer overall and progression-free survival rates when contrasted with those displaying lower CD4+ T cell infiltration.

Inclusion of blood pressure parameter increases predictive capability of severe obstructive sleep apnea: A decision tree approach.

Few studies included objective blood pressure (BP) to construct the predictive model of severe obstructive sleep apnea (OSA). This study used binary logistic regression model (BLRM) and the decision tree method (DTM) to constructed the predictive models for identifying severe OSA, and to compare the prediction capability between the two methods. Totally 499 adult patients with severe OSA and 1421 non-severe OSA controls examined at the Sleep Medicine Center of a tertiary hospital in southern Taiwan between October 2016 and April 2019 were enrolled. OSA was diagnosed through polysomnography. Data on BP, demographic characteristics, anthropometric measurements, comorbidity histories, and sleep questionnaires were collected. BLRM and DTM were separately applied to identify predictors of severe OSA. The performance of risk scores was assessed by area under the receiver operating characteristic curves (AUCs). In BLRM, body mass index (BMI) ≥27 kg/m2, and Snore Outcomes Survey score ≤55 were significant predictors of severe OSA (AUC 0.623). In DTM, mean SpO2 <96%, average systolic BP ≥135 mmHg, and BMI ≥39 kg/m2 were observed to effectively differentiate cases of severe OSA (AUC 0.718). The AUC for the predictive models produced by the DTM was higher in older adults than in younger adults (0.807 vs. 0.723) mainly due to differences in clinical predictive features. In conclusion, DTM, using a different set of predictors, seems more effective in identifying severe OSA than BLRM. Differences in predictors ascertained demonstrated the necessity for separately constructing predictive models for younger and older adults.

Accurate Collisional Cross Section Measurement by Multipass Cyclic Ion Mobility Spectrometry.

Ion mobility-mass spectrometry (IM-MS) is a powerful analytical tool for structural characterization. IM measurement provides collision cross section (CCS) values that facilitate analyte identification. While CCS values can be directly calculated from mobility measurements obtained using drift tube ion mobility spectrometry (DT-IMS), this method has limited mobility resolution due to the practical constraints on the length of the ion drift path. Consequently, DT-IMS cannot differentiate analytes with similar mobilities or resolve fine mobility features of individual ions. Cyclic IMS (cIMS) instruments leverage a cyclic path enabled by traveling wave ion mobility (TWIM) technology and offer increased mobility solution to address this challenge. While TWIM devices must first be calibrated to enable CCS measurements, current calibration strategies are primarily tailored for single-pass analyses. This preference is partly attributed to the challenges associated with multipass calibration methods, which require both calibrants and analytes to experience the same number of passes. Achieving this consistency can be complicated due to factors like peak splitting and diffusion, and may not be feasible for online IM-MS analyses. A recent report employed average ion velocities obtained from multiple measurements under different separation pathlengths as a path length-independent metric for CCS calibration. However, the ability to exploit this averaging approach is limited by observed variation in ion drift time/velocity in these measurements. In this study, we introduce a novel calibration strategy designed for multipass cIMS analyses, directly targeting the root cause for the path length- and mobility-dependent variations in ion drift time. With this method, we demonstrate that CCS values derived from multipass measurements closely align with those obtained from single-pass analyses, with an average deviation of 0.1%. We apply this method to characterize four isomeric trisaccharides. Our approach not only results in excellent agreement between our measured cIMSCCS values and the reported DTCCS values, with an average difference of only 0.5%, but also allows us to effectively identify subtle mobility characteristics of each compound and determine their respective CCS values. This level of detail and accuracy was previously unattainable using DT-IMS or single-pass cIMS measurements. We developed an algorithm for reconstructing arrival time distribution in cases where wrap-around has resulted in peak splitting. Collectively, the new calibration strategy and the reconstruction procedure maintain reproducibility and precision in CCS measurements while largely eliminating the need for meticulous selection of separation times. We expect that our method will empower researchers to harness the high mobility resolution offered by multipass cIMS analyses without compromising the accuracy of CCS measurement, making it appropriate for straightforward use across a wide range of applications.