Deep learning classification of ex vivo human colon tissues using spectroscopic optical coherence tomography.

Screening for colorectal cancer (CRC) with colonoscopy has improved patient outcomes; however, it remains the third leading cause of cancer-related mortality, novel strategies to improve screening are needed. Here, we propose an optical biopsy technique based on spectroscopic optical coherence tomography (OCT). Depth resolved OCT images are analyzed as a function of wavelength to measure optical tissue properties and used as input to machine learning algorithms. Previously, we used this approach to analyze mouse colon polyps. Here, we extend the approach to examine human biopsied colonic epithelial tissue samples ex vivo. Optical properties are used as input to a novel deep learning architecture, producing accuracy of up to 97.9% in discriminating tissue type. SOCT parameters are used to create false colored en face OCT images and deep learning classifications are used to enable visual classification by tissue type. This study advances SOCT toward clinical utility for analysis of colonic epithelium.

Chronic stress induces wide-spread hyperalgesia: The involvement of spinal CCK1 receptors.

Chronic primary pain (CPP) occurs in the absence of tissue injury and includes temporomandibular disorders (TMD), fibromyalgia syndrome (FMS) and irritable bowel syndrome (IBS). CPP is commonly considered a stress-related chronic pain and often presents as wide-spread pain or comorbid pain conditions in different regions of the body. However, whether prolonged stress can directly result in the development of CPP comorbidity remains unclear. In the present study, we adapted a 21 day heterotypic stress paradigm in mice and examined whether chronic stress induced wide-spread hyperalgesia, modeling comorbid CPP in the clinic. We found that chronic stress induced anxiety- and depression-like behaviors, and resulted in long-lasting wide-spread hyperalgesia over several body regions such as the orofacial area, hindpaw, thigh, upper back and abdomen in female mice. We further found that the expression of cholecystokinin (CCK)1 receptors was significantly increased in the L4-L5 spinal dorsal horn of the female mice after 14 and 21 day heterotypic stress compared with the control animals. Intrathecal injection of the CCK1 receptor antagonist CR-1505 blocked pain hypersensitivity in the subcervical body including the upper back, thigh, hindpaw and abdomen. These findings suggest that the upregulation of spinal CCK1 receptors after chronic stress contributes to the central mechanisms underlying the development of wide-spread hyperalgesia, and may provide a potential and novel central target for clinical treatment of CPP.

Outcomes and Hospital Service Use Among Patients With COPD in a Nurse- and Allied Health-Led Clinic.

Importance: Multidisciplinary disease management efforts enable the improvement in lung function among patients with chronic obstructive pulmonary disease (COPD), but there is little evidence of its association with risks of adverse health outcomes and health care service use. Objective: To examine the association between the use of a nurse- and allied health-led primary care clinic for respiratory patients, namely the Nurse and Allied Health Clinic-Respiratory Care (NAHC-Respiratory), and their risks of mortality and morbidity and health care service use. Design, Setting, and Participants: This territory-wide, population-based, propensity-matched, retrospective cohort study used data from the electronic health records of all patients who used public health care services in Hong Kong, China, from January 1, 2010, to December 31, 2019. All patients with COPD treated in public outpatient clinics between January 1, 2010, and December 31, 2014, were included. Patients who attended NAHC-Respiratory and usual care only were propensity score-matched at a 1:2 ratio. Data analyses were conducted between August 2023 and April 2024. Exposure: Attendance at NAHC-Respiratory. Main Outcomes and Measures: All-cause and cause-specific mortality, incidence of COPD complications, and use of emergency department and inpatient services until the end of 2019 were compared between the NAHC-Respiratory and usual care participants using Cox proportional hazard regression, Poisson regression, and log-link gamma regression models after matching. Results: This study included 9048 eligible patients after matching, including 3093 in the exposure group (2814 [91.0%] men; mean [SD] age, 69.8 [9.5] years) and 5955 in the reference group (5431 [91.2%] men; mean [SD] age, 69.5 [11.7] years). Compared with patients in the usual care-only group (reference), patients in the exposure group had lower risks of all-cause mortality (hazard ratio [HR], 0.84; 95% CI, 0.78-0.90) as well as pneumonia-caused (HR, 0.85; 95% CI, 0.74-0.97), respiratory-caused (HR, 0.86; 95% CI, 0.77-0.96), and cardiovascular-caused (HR, 0.74; 95% CI, 0.59-0.93) mortality. Exposure was associated with reduced rates of emergency department visits (incidence rate ratio [IRR], 0.92; 95% CI, 0.86-0.98) and hospitalization through emergency department (IRR, 0.89; 95% CI, 0.83-0.95). Conclusions: In this cohort study, the use of a nurse- and allied health-led clinic in primary care settings was associated with reduced risks of mortality and use of hospital services among patients with COPD. These findings emphasize the important role of health care workers other than physicians in disease management in the primary care setting. The NAHC-Respiratory model and service components can be used to help improve primary care programs to benefit more patients with COPD.

Association between asthma and COVID-19 severity during Omicron epidemic: a retrospective cohort study using real-world data.

BACKGROUND: The available evidence presented inconsistencies and inconclusive findings regarding the associations between co-existing asthma and mortality among COVID-19 patients. The objective of the current study is to investigate the relationship between asthma and severe outcomes after SARS-CoV-2 Omicron infection in an infection-naïve population. METHODS: A retrospective cohort study using propensity score matching was conducted. The COVID-19 patients requiring hospitalisation in Hong Kong from January 1, 2022, to November 13, 2022, an Omicron-predominated period, were identified. Severe clinical outcomes were defined as ICU admission and inpatient death after the first positive PCR results as well as a composite outcome of both. RESULTS: Of the 74,396 hospitalised COVID-19 patients admitted, 1,290 asthma patients and 18,641 non-asthma patients were included in the matched cohort. The rates of death and the composite outcome were 15·3% and 17·2%, respectively, among the non-asthma patients,12·2% and 13·6%, respectively, among the asthma patients, with adjusted hazard ratios equal to 0·775 (95% CI: 0·660-0·909) and 0·770 (95% CI: 0·662-0·895), respectively. The negative association was more apparent in the elderly and female groups. Asthma remained a factor that lowered the risk of disease severity even though the patients were not fully vaccinated with at least two doses. CONCLUSIONS: We used real-world data to demonstrate that asthma was not a risk factor for COVID-19 severity of the infections of Omicron variant, even though the patients were not fully vaccinated.

Coaxial transceiving LiDAR based on a silicon photonic optical phased array.

A high performance optical phased array (OPA) combined with frequency-modulated continuous-wave (FMCW) technology is essential for coherent all-solid-state light detection and ranging (LiDAR). In this work, we propose and experimentally demonstrate a coaxial transceiver based on a single OPA for a LiDAR system, which releases the off-chip circulator and collimator. The proposed scheme is demonstrated on the commonly used silicon-on-insulator (SOI) platform. For realizing the long optical grating antenna with only one-step etching, the bound state in the continuum is harnessed to simplify the fabrication process and ease the fabrication precision. Experimental results indicate that the OPA is with 0.076° vertical beam divergence under a 1.5 mm-long grating antenna. The measured field of view (FOV) is 40° × 8° without grating lobes under a wavelength band of 60 nm. The coaxial transceiver of the single OPA is also demonstrated with the FMCW method for ranging measurement at different angles.

Preparation of a hydrolyzed yeast ß-glucan chromium(III) complex and evaluation of its hypoglycemic activity and sub-acute toxicity.

Yeast ß-glucan (BYG) possesses extremely low solubility that has limited its applications. In this study, we hydrolyzed BYG using snail enzyme to obtain hydrolyzed yeast ß-glucan (HBYG) with desirable water solubility and hypoglycemic activity. On the basis of HBYG, HBYG­chromium(III) complex (HBYG-Cr) was synthesized. The molecular weight of the complex was 4.41 × 104 Da, and the content of trivalent chromium was 8.95 %. The hydroxyl groups of HBYG participated in the coordination and formed the chromium complex. The space conformations of HBYG exhibited remarkable changes after complex formation. HBYG-Cr existed mainly in an amorphous state and presented good dispersibility, and the surface was uneven. The hypoglycemic activity of HBYG-Cr was studied in db/db and C57 mice. The results showed that HBYG-Cr had good hypoglycemic activity. Histopathological studies demonstrated that the liver, kidney, pancreas, and skeletal muscle in the treatment group were significantly improved compared with those in the diabetic model group. The sub-acute toxicity of HBYG-Cr was studied in KM mice and the results indicated that the complex did not cause adverse reactions or toxic side effects. This study broadened the application of yeast ß-glucan and provided an important reference for the development of hypoglycemic functional foods and drugs.

Effectiveness of azvudine against severe outcomes among hospitalized COVID-19 patients in Xinjiang, China: a single-center, retrospective, matched cohort study.

BACKGROUND: Since the end of 2022, Azvudine was widely used to treat hospitalized coronavirus disease 2019 (COVID-19) patients in China. However, data on the real-world effectiveness of Azvudine against severe outcomes and post-COVID-19-conditions (PCC) among patients infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants was limited. This study evaluates the effectiveness of Azvudine in hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominance period. METHODS: From 1 November 2022 to 1 July 2023, an SARS-CoV-2 Omicron BA.5 dominant period, we conducted a single-center retrospective cohort study based on hospitalized patients with laboratory-confirmed SARS-CoV-2 infection from a tertiary hospital in Shihezi, China. Patients treated with Azvudine and usual care were propensity-score matched (PSM) at a 1:1 ratio to a control group in which patients received usual care only, with matching based on covariates such as sex, age, ethnicity, number of preexisting conditions, antibiotic use at admission, and baseline complete blood cell count. The primary outcomes were all-cause death and short-term (60 days) PCC post discharge. The secondary outcomes included the initiation of invasive mechanical ventilation and PCC at long-term post discharge (120 days). Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) of Azvudine treatment for both all-cause death and invasive mechanical ventilation, and logistic regression models were used to estimate the odds ratios (OR) for short-term and long-term PCC. Subgroup analyses were performed based on a part of the matched covariates. RESULTS: A total of 2,639 hospitalized patients with SARS-CoV-2 infection were initially identified, and 2,069 ineligible subjects were excluded from analyses. After matching, 297 Azvudine recipients and 297 matched controls were eligible for analyses. The incidence rate of all-cause death was relatively lower in the Azvudine group than in control group (0.007 per person, 95% confidence interval [CI]: 0.001, 0.024 vs 0.128, 95% CI: 0.092, 0.171), and the use of Azvudine was associated with a significantly lower risk of death (HR: 0.049, 95% CI: 0.012, 0.205). Subgroup analyses suggested protection of Azvudine against the risks of all-cause death among men, age over 65, patients without the preexisting conditions, and patients with antibiotics dispensed at admission. Statistical differences were not observed between the Azvudine group and the control group for the risks of invasive mechanical ventilation or short and long-term PCC. CONCLUSIONS: Our findings indicated that Azvudine was associated with lower risk of all-cause death among hospitalized patients with Omicron BA.5 infection in a real-world setting. Further investigation is needed to explore the effectiveness of Azvudine against the PCC after discharge.

This study aims to evaluate the real-world effectiveness of Azvudine among hospitalized COVID-19 patients during a SARS-CoV-2 Omicron BA.5 dominant epidemic phase. Cox proportional hazards (PH) regression models were employed to estimate the hazard ratios (HR) for all-cause death. We found that the use of Azvudine was associated with a significantly reduced risk of all-cause death among hospitalized patients with SARS-CoV-2 infection.

Association between meteorological variations and the superspreading potential of SARS-CoV-2 infections.

BACKGROUND: While many investigations examined the association between environmental covariates and COVID-19 incidence, none have examined their relationship with superspreading, a characteristic describing very few individuals disproportionally infecting a large number of people. METHODS: Contact tracing data of all the laboratory-confirmed COVID-19 cases in Hong Kong from February 16, 2020 to April 30, 2021 were used to form the infection clusters for estimating the time-varying dispersion parameter (kt), a measure of superspreading potential. Generalized additive models with identity link function were used to examine the association between negative-log kt (larger means higher superspreading potential) and the environmental covariates, adjusted with mobility metrics that account for the effect of social distancing measures. RESULTS: A total of 6,645 clusters covering 11,717 cases were reported over the study period. After centering at the median temperature, a lower ambient temperature at 10th percentile (18.2 °C) was significantly associated with a lower estimate of negative-log kt (adjusted expected change: -0.239 [95 % CI: -0.431 to -0.048]). While a U-shaped relationship between relative humidity and negative-log kt was observed, an inverted U-shaped relationship with actual vapour pressure was found. A higher total rainfall was significantly associated with lower estimates of negative-log kt. CONCLUSIONS: This study demonstrated a link between meteorological factors and the superspreading potential of COVID-19. We speculated that cold weather and rainy days reduced the social activities of individuals minimizing the interaction with others and the risk of spreading the diseases in high-risk facilities or large clusters, while the extremities of relative humidity may favor the stability and survival of the SARS-CoV-2 virus.

Research Progress of Baihe Gujin Decoction in the Treatment of Lung Cancer.

Baihe Gujin decoction is one of the most commonly used decoction in traditional Chinese medicine for the treatment of lung cancer. It can nourish yin and moisten the lung as well as prevent phlegm from forming and stop coughing. On the one hand, Baihe Gujin decoction is characterized with extensive application, proven efficacy, a long history, and high safety. On the other hand, Baihe Gujin decoction can induce apoptosis of tumor cells, improve immune function and inhibit inflammation. The main anti-tumor components of this include kaempferol, quercetin, isorhamnetin, glycyrrhizin and ß-sitosterol. Clinically, Baihe Gujin decoction can improve the adverse reactions caused by radiotherapy, chemotherapy and immunotherapy for lung cancer, enhance the quality of life of patients, and prolong their survival time. At present, there are a large number of clinical and basic researches on the treatment of lung cancer with Baihe Gujin decoction. In this paper, we mainly discussed the treatment of lung cancer with Baihe Gujin decoction through analyzing basic and clinical researches at home and abroad in the past 20 years. Through the discussion, we aimed to probe deeper into Baihe Gujin decoction for the treatment of lung cancer, thereby providing a broader idea for clinical diagnosis and treatment of lung cancer.

Association of nirmatrelvir-ritonavir with post-acute sequelae and mortality in patients admitted to hospital with COVID-19: a retrospective cohort study.

BACKGROUND: Studies have established the short-term efficacy of nirmatrelvir-ritonavir in managing COVID-19, yet its effect on post-COVID-19 condition, especially in patients admitted to hospital, remains understudied. This study aimed to examine the effect of nirmatrelvir-ritonavir on post-COVID-19 condition among patients admitted to hospital in Hong Kong. METHODS: This retrospective cohort study used real-world, territory-wide inpatient records, vaccination records, and confirmed COVID-19 case data from the Hong Kong Hospital Authority and Department of Health, The Government of the Hong Kong Special Administrative Region. Patients aged 18 years and older who tested positive for SARS-CoV-2 between March 11, 2022, and Oct 10, 2023, and who were admitted to hospital with COVID-19 were included. The treatment group included patients prescribed nirmatrelvir-ritonavir within 5 days of symptom onset, excluding those prescribed molnupiravir within 21 days, and the control group had no exposure to either nirmatrelvir-ritonavir or molnupiravir. The outcomes were post-acute inpatient death and 13 sequelae (congestive heart failure, atrial fibrillation, coronary artery disease, deep vein thrombosis, chronic pulmonary disease, acute respiratory distress syndrome, interstitial lung disease, seizure, anxiety, post-traumatic stress disorder, end-stage renal disease, acute kidney injury, and pancreatitis). These outcomes were evaluated starting at 21 days after the positive RT-PCR date in each respective cohort constructed for the outcome. Standardised mortality ratio weights were applied to balance covariates, and Cox proportional hazards regression was used to investigate the relationship between nirmatrelvir-ritonavir and outcomes. FINDINGS: 136 973 patients were screened for inclusion, among whom 50 055 were eligible and included in the analysis (24 873 [49·7%] were female and 25 182 [50·3%] were male). 15 242 patients were prescribed nirmatrelvir-ritonavir during acute COVID-19 and 23 756 patients were included in the control group; 11 057 patients did not meet our definition for the exposed and unexposed groups. Patients were followed up for a median of 393 days (IQR 317-489). In the nirmatrelvir-ritonavir group compared with the control group, there was a significantly lower hazard of post-acute inpatient death (hazard ratio 0·62 [95% CI 0·57-0·68]; p<0·0001), congestive heart failure (0·70 [0·58-0·85]; p=0·0002), atrial fibrillation (0·63 [0·52-0·76]; p<0·0001), coronary artery disease (0·71 [0·59-0·85]; p=0·0002), chronic pulmonary disease (0·68 [0·54-0·86]; p=0·0011), acute respiratory distress syndrome (0·71 [0·58-0·86]; p=0·0007), interstitial lung disease (0·17 [0·04-0·75]; p=0·020), and end-stage renal disease (0·37 [0·18-0·74]; p=0·0049). There was no evidence indicating difference between the groups in deep vein thrombosis, seizure, anxiety, post-traumatic stress disorder, acute kidney injury, and pancreatitis. INTERPRETATION: This study showed extended benefits of nirmatrelvir-ritonavir for reducing the risk of post-acute inpatient death as well as cardiovascular and respiratory complications among patients admitted to hospital with COVID-19. Further research is essential to uncover the underlying mechanisms responsible for these observed negative associations and to devise effective strategies for preventing the onset of post-acute sequelae. FUNDING: Health and Medical Research Fund, Research Grants Council theme-based research schemes, and Research Grants Council Collaborative Research Fund.

Transmission risks of Omicron BA.5 following inactivated COVID-19 vaccines among children and adolescents in China.

BACKGROUND: As SARS-CoV-2 Omicron variants circulating globally since 2022, assessing the transmission characteristics, and the protection of vaccines against emerging Omicron variants among children and adolescents are needed for guiding the control and vaccination policies. METHODS: We conducted a retrospective cohort study for SARS-CoV-2 infections and close contacts aged <18 years from an outbreak seeded by Omicron BA.5 variants. The secondary attack rate (SAR) was calculated and the protective effects of two doses of inactivated vaccine (mainly Sinopharm /BBIBP-CorV) within a year versus one dose or two doses above a year after vaccination against the transmission and infection of Omicron BA.5 were estimated. RESULTS: A total of 3442 all-age close contacts of 122 confirmed SARS-CoV-2 infections aged 0-17 years were included. The SAR was higher in the household setting and for individuals who received a one-dose inactivated vaccine or those who received a two-dose for more than one year, with estimates of 28.5% (95% credible interval [CrI]: 21.1, 37.7) and 55.3% (95% CrI: 24.4, 84.8), respectively. The second dose of inactivated vaccine conferred substantial protection against all infection and transmission of Omicron BA.5 variants within a year. CONCLUSIONS: Our findings support the rollout of the second dose of inactivated vaccine for children and adolescents during the Omciron BA.5 predominant epidemic phase. Given the continuous emergence of SARS-CoV-2 variants, monitoring the transmission risk and corresponding vaccine effectiveness against SARS-CoV-2 variants among children and adolescents is important to inform control strategy.

Children and adolescents have reported suffering less severe outcomes from the SARS-CoV-2 Omicron variant. However, the risk of transmission and vaccine effectiveness among this population group is not well studied. Here, we used contact tracing data that was collected during an Omicron BA.5 outbreak from Urumqi, China, before the exit of "zero-COVID" measures, to evaluate the spread of SARS-CoV-2 infection among those age under 18 years, and the effectiveness of inactivated vaccine regimens. Our findings indicate there is a high rate of transmission among children and adolescents in a household setting and receiving two doses of inactivated COVID-19 vaccination within a year was more effective than a single dose or two doses given more than a year apart. These findings highlight the importance of tracking transmission and vaccine effectiveness of novel SARS-CoV-2 variants in younger populations to inform control strategies.

Pseudorabies virus hijacks the Rab6 protein to promote viral assembly and egress.

Pseudorabies virus (PRV) is recognized as the aetiological agent responsible for Aujeszky's disease, or pseudorabies, in swine populations. Rab6, a member of the small GTPase family, is implicated in various membrane trafficking processes, particularly exocytosis regulation. Its involvement in PRV infection, however, has not been documented previously. In our study, we observed a significant increase in the Rab6 mRNA and protein levels in both PK-15 porcine kidney epithelial cells and porcine alveolar macrophages, as well as in the lungs and spleens of mice infected with PRV. The overexpression of wild-type Rab6 and its GTP-bound mutant facilitated PRV proliferation, whereas the GDP-bound mutant form of Rab6 had no effect on viral propagation. These findings indicated that the GTPase activity of Rab6 was crucial for the successful spread of PRV. Further investigations revealed that the reduction in Rab6 levels through knockdown significantly hampered PRV proliferation and disrupted virus assembly and egress. At the molecular level, Rab6 was found to interact with the PRV glycoproteins gB and gE, both of which are essential for viral assembly and egress. Our results collectively suggest that PRV exploits Rab6 to expedite its assembly and egress and identify Rab6 as a promising novel target for therapeutic treatment for PRV infection.

Daily Low-Level Red Light for Spherical Equivalent Error and Axial Length in Children With Myopia: A Randomized Clinical Trial.

Importance: Treatments are needed to slow progression of or reduce incidence of myopia. Objective: To evaluate the efficacy and safety of daily 650-nm low-level red light (LLRL) for myopia treatment. Design, Setting, and Participants: Single-masked, randomized clinical trial at 1 site in China. Baseline measurements were completed from August to September 2021. Participants were children aged 6 to 12 years with spherical equivalent error (SER) of -6 diopters (D) to 3 D. Data were analyzed from March to July 2023. Interventions: Irradiation daily with 650-nm LLRL for 3 minutes twice daily 4 or more hours apart or no intervention. Main Outcomes and Measures: Primary outcomes were changes in cycloplegia SER and axial length (AL) at 6- and 12-month follow-up visits. Safety was assessed on masked fundus photograph evaluations. Results: A total of 336 children were randomly allocated into the LLRL group or control group in a 1:1 ratio. The control group contained 86 female patients (51.2%), and the treatment group contained 90 female patients (53.6%). The mean (SD) age, SER, and AL were 9.0 (1.9) years, -1.3 (1.5) D, and 23.8 (1.0) mm for all patients. A total of 161 (95.8%) in the LLRL group and 159 (94.6%) in the control group returned for the 6-month follow-up. A total of 157 (93.5%) in the LLRL group and 152 (90.5%) in the control group returned for the 12-month follow-up. Mean (SD) changes in SER were 0.15 (0.16) D and -0.26 (0.21) D for the LLRL group and the control group, respectively (difference, -0.41 D; 95% CI, -0.48 to -0.34 D; P < .001), at 6 months and 0.24 (0.27) D and -0.65 (0.33) D for the LLRL group and the control group, respectively (difference, -0.89 D; 95% CI, -0.95 to -0.83 D; P < .001), at 12 months. Mean (SD) changes in AL were -0.06 (0.08) mm and 0.13 (0.12) mm for the LLRL group and control group, respectively (difference, 0.19 mm; 95% CI, 0.16 to 0.22 mm; P < .001), at 6 months and -0.11 (0.10) mm and 0.26 (0.16) mm for the LLRL group and control group, respectively (difference, 0.37 mm; 95% CI, 0.34 to 0.40 mm; P < .001). Masked fundus photograph review did not identify retinal changes in either group. Conclusions and relevance: These findings suggest daily use of 650-nm LLRL for 1 year can slow progression of SER and AL without safety concerns identified. Confirmation of these findings at independent sites seems warranted, as well as determining whether these effects can be sustained with or without continued treatment and whether LLRL has any effect on pathological myopia. Trial Registration: ChiCTR2200058963.

Projection of dengue fever transmissibility under climate change in South and Southeast Asian countries.

Vector-borne infectious disease such as dengue fever (DF) has spread rapidly due to more suitable living environments. Considering the limited studies investigating the disease spread under climate change in South and Southeast Asia, this study aimed to project the DF transmission potential in 30 locations across four South and Southeast Asian countries. In this study, weekly DF incidence data, daily mean temperature, and rainfall data in 30 locations in Singapore, Sri Lanka, Malaysia, and Thailand from 2012 to 2020 were collected. The effects of temperature and rainfall on the time-varying reproduction number (Rt) of DF transmission were examined using generalized additive models. Projections of location-specific Rt from 2030s to 2090s were determined using projected temperature and rainfall under three Shared Socioeconomic Pathways (SSP126, SSP245, and SSP585), and the peak DF transmissibility and epidemic duration in the future were estimated. According to the results, the projected changes in the peak Rt and epidemic duration varied across locations, and the most significant change was observed under middle-to-high greenhouse gas emission scenarios. Under SSP585, the country-specific peak Rt was projected to decrease from 1.63 (95% confidence interval: 1.39-1.91), 2.60 (1.89-3.57), and 1.41 (1.22-1.64) in 2030s to 1.22 (0.98-1.51), 2.09 (1.26-3.47), and 1.37 (0.83-2.27) in 2090s in Singapore, Thailand, and Malaysia, respectively. Yet, the peak Rt in Sri Lanka changed slightly from 2030s to 2090s under SSP585. The epidemic duration in Singapore and Malaysia was projected to decline under SSP585. In conclusion, the change of peak DF transmission potential and disease outbreak duration would vary across locations, particularly under middle-to-high greenhouse gas emission scenarios. Interventions should be considered to slow down global warming as well as the potential increase in DF transmissibility in some locations of South and Southeast Asia.

Exploring the molecular biology of ischemic cardiomyopathy based on ferroptosis­related genes.

Ischemic cardiomyopathy (ICM) is a serious cardiac disease with a very high mortality rate worldwide, which causes myocardial ischemia and hypoxia as the main damage. Further understanding of the underlying pathological processes of cardiomyocyte injury is key to the development of cardioprotective strategies. Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of lipid hydroperoxides to lethal levels, resulting in oxidative damage to the cell membrane. The current understanding of the role and regulation of ferroptosis in ICM is still limited, especially in the absence of evidence from large-scale transcriptomic data. Through comprehensive bioinformatics analysis of human ICM transcriptome data obtained from the Gene Expression Omnibus database, the present study identified differentially expressed ferroptosis-related genes (DEFRGs) in ICM. Subsequently, their potential biological mechanisms and cross-talk were analyzed, and hub genes were identified by constructing protein-protein interaction networks. Ferroptosis features such as reactive oxygen species generation, changes in ferroptosis marker proteins, iron ion aggregation and lipid oxidation, were identified in the H9c2 anoxic reoxygenation injury model. Finally, the diagnostic ability of Gap junction alpha-1 (GJA1), Solute carrier family 40 member 1 (SLC40A1), Alpha-synuclein (SNCA) were identified through receiver operating characteristic curves and the expression of DEFRGs was verified in an in vitro model. Furthermore, potential drugs (retinoic acid) that could regulate ICM ferroptosis were predicted based on key DEFRGs. The present article presents new insights into the role of ferroptosis in ICM, investigating the regulatory role of ferroptosis in the pathological process of ICM and advocating for ferroptosis as a potential novel therapeutic target for ICM based on evidence from the ICM transcriptome.

Association of glycogen synthase kinase-3ß with cognitive impairment in type 2 diabetes patients: a six-year follow-up study.

Background: Our previous multicenter case-control study showed that aging, up-regulation of platelet glycogen synthase kinase-3ß (GSK-3ß), impaired olfactory function, and ApoE ϵ4 genotype were associated with cognitive decline in type 2 diabetes mellitus (T2DM) patients. However, the causal relationship between these biomarkers and the development of cognitive decline in T2DM patients remains unclear. Methods: To further investigate this potential relationship, we designed a 6-year follow-up study in 273 T2DM patients with normal cognitive in our previous study. Baseline characteristics of the study population were compared between T2DM patients with and without incident mild cognitive impairment (MCI). We utilized Cox proportional hazard regression models to assess the risk of cognitive impairment associated with various baseline biomarkers. Receiver operating characteristic curves (ROC) were performed to evaluate the diagnostic accuracy of these biomarkers in predicting cognitive impairment. Results: During a median follow-up time of 6 years (with a range of 4 to 9 years), 40 patients (16.13%) with T2DM developed MCI. Participants who developed incident MCI were more likely to be older, have a lower education level, have more diabetic complications, a higher percentage of ApoE ϵ4 allele and a higher level of platelet GSK-3ß activity (rGSK-3ß) at baseline (P<0.05). In the longitudinal follow-up, individuals with higher levels of rGSK-3ß were more likely to develop incident MCI, with an adjusted hazard ratio (HR) of 1.60 (95% confidence interval [CI] 1.05, 2.46), even after controlling for potential confounders. The AUC of the combination of age, rGSK-3ß and ApoEϵ4 allele predicted for incident MCI was 0.71. Conclusion: Platelet GSK-3ß activity could be a useful biomarker to predict cognitive decline, suggesting the feasibility of identifying vulnerable population and implementing early prevention for dementia.

Soybean steroids improve crop abiotic stress tolerance and increase yield.

Sterols have long been associated with diverse fields, such as cancer treatment, drug development, and plant growth; however, their underlying mechanisms and functions remain enigmatic. Here, we unveil a critical role played by a GmNF-YC9-mediated CCAAT-box transcription complex in modulating the steroid metabolism pathway within soybeans. Specifically, this complex directly activates squalene monooxygenase (GmSQE1), which is a rate-limiting enzyme in steroid synthesis. Our findings demonstrate that overexpression of either GmNF-YC9 or GmSQE1 significantly enhances soybean stress tolerance, while the inhibition of SQE weakens this tolerance. Field experiments conducted over two seasons further reveal increased yields per plant in both GmNF-YC9 and GmSQE1 overexpressing plants under drought stress conditions. This enhanced stress tolerance is attributed to the reduction of abiotic stress-induced cell oxidative damage. Transcriptome and metabolome analyses shed light on the upregulation of multiple sterol compounds, including fucosterol and soyasaponin II, in GmNF-YC9 and GmSQE1 overexpressing soybean plants under stress conditions. Intriguingly, the application of soybean steroids, including fucosterol and soyasaponin II, significantly improves drought tolerance in soybean, wheat, foxtail millet, and maize. These findings underscore the pivotal role of soybean steroids in countering oxidative stress in plants and offer a new research strategy for enhancing crop stress tolerance and quality from gene regulation to chemical intervention.