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1.
Front Plant Sci ; 15: 1409194, 2024.
Article in English | MEDLINE | ID: mdl-38966142

ABSTRACT

Introduction: Cotton yield estimation is crucial in the agricultural process, where the accuracy of boll detection during the flocculation period significantly influences yield estimations in cotton fields. Unmanned Aerial Vehicles (UAVs) are frequently employed for plant detection and counting due to their cost-effectiveness and adaptability. Methods: Addressing the challenges of small target cotton bolls and low resolution of UAVs, this paper introduces a method based on the YOLO v8 framework for transfer learning, named YOLO small-scale pyramid depth-aware detection (SSPD). The method combines space-to-depth and non-strided convolution (SPD-Conv) and a small target detector head, and also integrates a simple, parameter-free attentional mechanism (SimAM) that significantly improves target boll detection accuracy. Results: The YOLO SSPD achieved a boll detection accuracy of 0.874 on UAV-scale imagery. It also recorded a coefficient of determination (R2) of 0.86, with a root mean square error (RMSE) of 12.38 and a relative root mean square error (RRMSE) of 11.19% for boll counts. Discussion: The findings indicate that YOLO SSPD can significantly improve the accuracy of cotton boll detection on UAV imagery, thereby supporting the cotton production process. This method offers a robust solution for high-precision cotton monitoring, enhancing the reliability of cotton yield estimates.

2.
Water Res ; 261: 122012, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38968737

ABSTRACT

The complex hydrological conditions caused by the backwater effect at the confluence inevitably modify the geochemical processes of elements. However, there is still a lack of comprehensive understanding regarding the precise transformation mechanisms of nutrients in large river systems. This study aimed to investigate the hydrodynamic characteristics and their impact on phosphorus transfer in the lower Han River, which is influenced by backwater from the Yangtze River (the largest river in China). By establishing a hydrodynamic-water quality model, we have determined that the discharge ratio (the ratio of flow between the Han River discharge and the Yangtze River discharge) can be utilized as a representative indicator of the backwater effect from the Yangtze River on the Han River. Three distinct patterns were identified in this study: mixing, backwater, and intrusion. The corresponding discharge ratio values were categorized as >0.08, 0.01∼0.08, and <0.01 respectively. Additionally, the extent of the backwater zone was determined, revealing that the length of the backwater zone increased from 50 km (XG) to 100 km (FS) as the discharge ratio decreased from 0.08 to 0.01. Furthermore, it was observed that the water level at the confluence rose from 2.52 m to 6.83 m in accordance with these changes in discharge ratio values. The migration pattern of phosphorus primarily involved the settling and retention of particulate phosphorus, particularly the labile particulate organic phosphorus (LOP) and dissolved organic phosphorus (DOP). When the confluent patterns became the intrusion pattern, the backwater zone expanded to 150 m (XT), causing a 10.40 m increase in water level at the confluence. An intrusion zone formed, and its phosphorus concentrations were same as Yangtze River's. Above the intrusion area, a backwater region formed and its concentrations of LOP and DOP decreased, while the concentration of PO43- increased due to the release from resuspended particles. This release was induced by higher velocity of bottom water brought about by the water exchange of two rivers. The discharge ratio of 0.01-0.08 resulted in the sedimentation of LOP and DOP, causing the lower Han River to act as a "sink" for phosphorus, potentially exacerbating phosphorus pollution. Higher discharge ratios in spring led to phosphorus release from sediment, increasing dissolved phosphorus concentrations and raising the risk of algal blooms in the lower Han River. These findings have significant implications for larger rivers worldwide and provide insights into strategies for ecological management and prevention of algal blooms.

3.
Lancet Planet Health ; 8(7): e463-e475, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38969474

ABSTRACT

BACKGROUND: Nipah virus is a zoonotic paramyxovirus responsible for disease outbreaks with high fatality rates in south and southeast Asia. However, knowledge of the potential geographical extent and risk patterns of the virus is poor. We aimed to establish an integrated spatiotemporal and phylogenetic database of Nipah virus infections in humans and animals across south and southeast Asia. METHODS: In this geospatial modelling analysis, we developed an integrated database containing information on the distribution of Nipah virus infections in humans and animals from 1998 to 2021. We conducted phylodynamic analysis to examine the evolution and migration pathways of the virus and meta-analyses to estimate the adjusted case-fatality rate. We used two boosted regression tree models to identify the potential ecological drivers of Nipah virus occurrences in spillover events and endemic areas, and mapped potential risk areas for Nipah virus endemicity. FINDINGS: 749 people and eight bat species across nine countries were documented as being infected with Nipah virus. On the basis of 66 complete genomes of the virus, we identified two clades-the Bangladesh clade and the Malaysia clade-with the time of the most recent common ancestor estimated to be 1863. Adjusted case-fatality rates varied widely between countries and were higher for the Bangladesh clade than for the Malaysia clade. Multivariable meta-regression analysis revealed significant relationships between case-fatality rate estimates and viral clade (p=0·0021), source country (p=0·016), proportion of male patients (p=0·036), and travel time to health-care facilities (p=0·036). Temperature-related bioclimate variables and the probability of occurrence of Pteropus medius were important contributors to both the spillover and the endemic infection models. INTERPRETATION: The suitable niches for Nipah virus are more extensive than previously reported. Future surveillance efforts should focus on high-risk areas informed by updated projections. Specifically, intensifying zoonotic surveillance efforts, enhancing laboratory testing capacity, and implementing public health education in projected high-risk areas where no human cases have been reported to date will be crucial. Additionally, strengthening wildlife surveillance and investigating potential modes of transmission in regions with documented human cases is needed. FUNDING: The Key Research and Development Program of China.


Subject(s)
Henipavirus Infections , Nipah Virus , Nipah Virus/physiology , Henipavirus Infections/epidemiology , Henipavirus Infections/transmission , Humans , Animals , Chiroptera/virology , Asia, Southeastern/epidemiology , Phylogeny , Zoonoses/epidemiology , Zoonoses/virology
4.
Front Neurol ; 15: 1365860, 2024.
Article in English | MEDLINE | ID: mdl-38974682

ABSTRACT

Objectives: This study aimed to investigate the management of vascular risk factors, with a specific focus on understanding the various factors affecting risk factor control through an in-depth analysis of clinical data and a longitudinal follow-up of patients who have experienced ischemic strokes. Methods: A total of 1,572 participants were included in the analysis. We assessed thresholds for blood pressure (BP), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin (HbA1c) levels to uncover the contextual conditions and factors affecting vascular risk factor control. Moreover, the study also scrutinized medication compliance at intervals of 3, 6, and 12 months post-onset. Logistic regression was used to adjust for confounding factors. Results: At 3, 6, and 12 months, BP,LDL, hemoglobin control targets were achieved in 50.7, 51.8, and 50.6%; 51.5, 59.4, and 50.6%; 48.1, 44.0, and 48.4%,respectively. Notably, age was associated with the achievement of BP control (odds ratio [OR], 0.96; 95% confidence intervals [CI], 0.94-0.98; p < 0.0001). Ethnic minorities (OR, 4.23; 95% CI, 1.19-15.09; p = 0.02) and individuals with coronary heart disease (OR, 0.5; 95% CI, 0.3-1.0; p = 0.05) experienced decreased BP control ratios. A previous history of stroke (OR, 1.7; 95% CI, 1.0-2.8; p = 0.03) and unrestricted alcohol consumption (OR, 3.3; 95% CI, 1.0-11.1; p = 0.05) was significantly associated with the achievement of lipid control. Furthermore, lifestyle modifications were significantly correlated with the achievement of BP control (OR, 0.19; 95% CI, 0.12-0.30; p < 0.01), blood glucose control (OR, 0.03; 95% CI, 0.01-0.08; p < 0.01), and blood lipid control (OR, 0.26; 95% CI, 0.16-0.42; p < 0.01). The absence of regular physical activity was associated with lower rates of glycemic (OR, 0.14; 95% CI, 0.06-0.36; p < 0.01) and lipid controls (OR, 0.55; 95% CI, 0.33-0.90; p = 0.01). Over time, overall medication compliance declined. Conclusion: Within the cohort of patients under medication, the compliance rate concerning vascular risk factors remains unsatisfactory. Attention should be paid to compliance with secondary prevention medications and enhance the control of vascular risk factors, as compliance emerges as the key to effective prevention.

5.
Aging Med (Milton) ; 7(3): 393-405, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38975310

ABSTRACT

Objective: Chronological age (CAge), biological age (BAge), and accelerated age (AAge) are all important for aging-related diseases. CAge is a known risk factor for benign prostatic hyperplasia (BPH); However, the evidence of association of BAge and AAge with BPH is limited. This study aimed to evaluate the association of CAge, Bage, and AAge with BPH in a large prospective cohort. Method: A total of 135,933 males without BPH at enrolment were extracted from the UK biobank. We calculated three BAge measures (Klemera-Doubal method, KDM; PhenoAge; homeostatic dysregulation, HD) based on 16 biomarkers. Additionally, we calculated KDM-BAge and PhenoAge-BAge measures based on the Levine method. The KDM-AAge and PhenoAge-AAge were assessed by the difference between CAge and BAge and were standardized (mean = 0 and standard deviation [SD] = 1). Cox proportional hazard models were applied to assess the associations of CAge, Bage, and AAge with incident BPH risk. Results: During a median follow-up of 13.150 years, 11,811 (8.690%) incident BPH were identified. Advanced CAge and BAge measures were associated with an increased risk of BPH, showing threshold effects at a later age (all P for nonlinearity <0.001). Nonlinear relationships between AAge measures and risk of BPH were also found for KDM-AAge (P = 0.041) and PhenoAge-AAge (P = 0.020). Compared to the balance comparison group (-1 SD < AAge < 1 SD), the accelerated aging group (AAge > 2 SD) had a significantly elevated BPH risk with hazard ratio (HR) of 1.115 (95% CI, 1.000-1.223) for KDM-AAge and 1.180 (95% CI, 1.068-1.303) for PhenoAge-AAge, respectively. For PhenoAge-AAge, subgroup analysis of the accelerated aging group showed an increased HR of 1.904 (95% CI, 1.374-2.639) in males with CAge <50 years and 1.233 (95% CI, 1.088-1.397) in those having testosterone levels <12 nmol/L. Moreover, AAge-associated risk of BPH was independent of and additive to genetic risk. Conclusions: Biological aging is an independent and modifiable risk factor for BPH. We suggest performing active health interventions to slow biological aging, which will help mitigate the progression of prostate aging and further reduce the burden of BPH.

6.
Surg Endosc ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38977497

ABSTRACT

OBJECTIVE: To investigate the significance of endoscopic grading (Hill's classification) of gastroesophageal flap valve (GEFV) in the examination of patients with gastroesophageal reflux disease (GERD). METHODS: One hundred and sixty-two patients undergoing gastroscopy in the Department of Gastroenterology, Xingyi People's Hospital between Apr. 2022 and Sept. 2022 were selected by convenient sampling, and data such as GEFV grade, and findings of esophageal high-resolution manometry (HRM) and esophageal 24-h pH/impedance reflux monitoring, and Los Angeles (LA) classification of reflux esophagitis (RE) were collected and compared. RESULTS: Statistically significant differences in age (F = 9.711, P < 0.001) and hiatal hernia (χ = 35.729, P < 0.001) were observed in patients with different GEFV grades. The resting LES pressures were 12.12 ± 2.79, 10.73 ± 2.68, 9.70 ± 2.29, and 8.20 ± 2.77 mmHg (F = 4.571, P < 0.001) and LES lengths were 3.30 ± 0.70, 3.16 ± 0.68, 2.35 ± 0.83, and 2.45 ± 0.62 (F = 3.789, P = 0.011), respectively, in patients with GEFV grades I-IV. DeMeester score (Z = 5.452, P < 0.001), AET4 (Z = 5.614, P < 0.001), acid reflux score (upright) (Z = 7.452, P < 0.001), weak acid reflux score (upright) (Z = 3.121, P = 0.038), liquid reflux score (upright) (Z = 3.321, P = 0.031), acid reflux score (supine) (Z = 6.462, P < 0.001), mixed reflux score (supine) (Z = 3.324, P = 0.031), gas reflux score (supine) (Z = 3.521, P = 0.024) were different in patients with different GEFV grades, with statistically significant differences. Pearson correlation analysis revealed a positive correlation between RE grade and LA classification of GERD (r = 0.662, P < 0.001), and the severity of RE increased gradually with the increase of the Hill grades of GEFV. CONCLUSION: The Hill grade of GEFV is related to age, hiatal hernia, LES pressure, and the consequent development and severity of acid reflux and RE. Evaluation of esophageal motility and reflux based on the Hill grade of GEFV is of significance for the diagnosis and treatment of GERD.

7.
Am J Hematol ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980207

ABSTRACT

Patients with steroid-resistant or relapsed immune thrombocytopenia (ITP) suffer increased bleeding risk and impaired quality of life. Baricitinib, an oral Janus-associated kinases (JAK) inhibitor, could alleviate both innate and adaptive immune disorders without inducing thrombocytopenia in several autoimmune diseases. Accordingly, an open-label, single-arm, phase 2 trial (NCT05446831) was initiated to explore the safety and efficacy of baricitinib in ITP. Eligible patients were adults with primary ITP who were refractory to corticosteroids and at least one subsequent treatment, and had platelet counts below 30 × 109/L at enrolment. Participants received baricitinib 4 mg daily for 6 months. The primary endpoint was durable response at the 6-month follow-up. A total of 35 patients were enrolled. Durable response was achieved in 20 patients (57.1%, 95% confidence interval, 39.9 to 74.4), and initial response in 23 (65.7%) patients. For patients responding to baricitinib, the median time to response was 12 (IQR 6-20) days, and the median peak platelet count was 94 (IQR 72-128) × 109/L. Among the 27 patients undergoing extend observation, 12 (44.4%) remained responsive for a median duration of approximately 20 weeks after baricitinib discontinuation. Adverse events were reported in 11 (31.4%) patients, including infections in 6 (17.1%) patients during the treatment period. Treatment discontinuation due to an adverse event was reported in 2 (5.7%) patients. Evidence from this pilot study suggested that baricitinib might be a novel candidate for the armamentarium of ITP-modifying agents. Future studies are warranted to validate the safety, efficacy, and optimal dosing of baricitinib in patients with ITP.

8.
Small ; : e2403570, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38966891

ABSTRACT

In organic solar cells (OSCs), electron acceptors have undergone multiple updates, from the initial fullerene derivatives, to the later acceptor-donor-acceptor type non-fullerene acceptors (NFAs), and now to Y-series NFAs, based on which efficiencies have reached over 19%. However, the key property responsible for further improved efficiency from molecular structure design is remained unclear. Herein, the material properties are comprehensively scanned by selecting PC71BM, IT-4F, and L8-BO as the representatives for different development stages of acceptors. For comparison, asymmetric acceptor of BTP-H5 with desired loosely bounded excitons is designed and synthesized. It's identified that the reduction of intrinsically exciton binding energy (Eb) and the enhancement of exciton delocalization capability act as the key roles in boosting the performance. Notably, 100 meV reduction in Eb has been observed from PC71BM to BTP-H5, correspondingly, electron-hole pair distance of BTP-H5 is almost two times over PC71BM. As a result, efficiency is improved from 40% of S-Q limit for PC71BM-based OSC to 60% for BTP-H5-based one, which achieves an efficiency of 19.07%, among the highest values for binary OSCs. This work reveals the confirmed function of exciton delocalization capability quantitatively in pushing the efficiency of OSCs, thus providing an enlightenment for future molecular design.

9.
Clin Transplant ; 38(7): e15396, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38967600

ABSTRACT

INTRODUCTION: Central nervous system leukemia (CNSL) remains a serious complication in patients with acute myeloid leukemia (AML) and an ambiguous prognostic factor for those receiving allo-geneic hematopoiesis stem cell transplantation (allo-HSCT). It is unknown whether using more sensitive tools, such as multiparameter flow cytometry (MFC), to detect blasts in the cerebrospinal fluid (CSF) would have an impact on outcome. METHODS: We retrospectively analyzed the clinical outcomes of 1472 AML patients with or without cytology or MFC positivity in the CSF before transplantation. Abnormal CSF (CSF+) was detected via conventional cytology and MFC in 44 patients at any time after diagnosis. A control group of 175 CSF-normal (CSF-) patients was generated via propensity score matching (PSM) analyses according to sex, age at transplant, and white blood cell count at diagnosis. RESULTS: Compared to those in the CSF-negative group, the conventional cytology positive and MFC+ groups had comparable 8-year nonrelapse mortality (NRM) (4%, 4%, and 6%, p = 0.82), higher cumulative incidence of relapse (CIR) (14%, 31%, and 32%, p = 0.007), lower leukemia-free survival (LFS) (79%, 63%, and 64%, p = 0.024), and overall survival (OS) (83%, 63%, and 68%, p = 0.021), with no significant differences between the conventional cytology positive and MFC+ groups. Furthermore, multivariate analysis confirmed that CSF involvement was an independent factor affecting OS and LFS. CONCLUSION: Our results indicate that pretransplant CSF abnormalities are adverse factors independently affecting OS and LFS after allotransplantation in AML patients.


Subject(s)
Flow Cytometry , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Transplantation, Homologous , Humans , Female , Male , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/cerebrospinal fluid , Leukemia, Myeloid, Acute/mortality , Retrospective Studies , Adult , Prognosis , Middle Aged , Follow-Up Studies , Adolescent , Hematopoietic Stem Cell Transplantation/adverse effects , Survival Rate , Young Adult , Graft vs Host Disease/etiology , Graft vs Host Disease/cerebrospinal fluid , Graft vs Host Disease/diagnosis , Graft vs Host Disease/mortality , Aged , Child , Cytology
10.
Adv Sci (Weinh) ; : e2406333, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38981044

ABSTRACT

Mortality rates due to lung cancer are high worldwide. Although PD-1 and PD-L1 immune checkpoint inhibitors boost the survival of patients with non-small-cell lung cancer (NSCLC), resistance often arises. The Warburg Effect, which causes lactate build-up and potential lysine-lactylation (Kla), links immune dysfunction to tumor metabolism. The role of non-histone Kla in tumor immune microenvironment and immunotherapy remains to be clarified. Here, global lactylome profiling and metabolomic analyses of samples from patients with NSCLC is conducted. By combining multi-omics analysis with in vitro and in vivo validation, that intracellular lactate promotes extracellular lipolysis through lactyl-APOC2 is revealed. Mechanistically, lactate enhances APOC2 lactylation at K70, stabilizing it and resulting in FFA release, regulatory T cell accumulation, immunotherapy resistance, and metastasis. Moreover, the anti-APOC2K70-lac antibody that sensitized anti-PD-1 therapy in vivo is developed. This findings highlight the potential of anti lactyl-APOC2-K70 approach as a new combination therapy for sensitizing immunotherapeutic responses.

11.
Int J Biol Macromol ; 275(Pt 1): 133675, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38971287

ABSTRACT

With growing concerns about postharvest spoilage of fruits, higher requirements have been placed on high-performance and sustainable active packaging materials. In this study, we prepared curcumin-based functional composite films using chitosan (CS) and Tenebrio molitor larvae protein (TMP) as the substrates. The effects of curcumin concentration on the structural and physicochemical properties of the composite films were determined. Curcumin was equally distributed in the polymer film through physical interactions. Furthermore, the curcumin composite film with 0.3 % addition exhibited a 27.39 % increase in elongation at break (EBA), a 37.04 % increase in the water vapor barrier, and strong UV-blocking properties and antioxidant activity compared with the control film (CS/TMP). The degradation experiment of the composite film on natural soil revealed that the composite film exhibited good biodegradability and environmental protection. Furthermore, the applicability of functional composite films for preserving blueberries was investigated. Compared with the control film and polyethylene (PE) films, the prepared composite films packaging treatment reduced the decay rate and weight loss rate of blueberries during storage, delayed softening and aging, and maintained the quality of blueberries. Using sustainable protein resources (TMP) and natural polysaccharides as packaging materials provides an economically, feasible and sustainable way to achieve the functional preservation of biomass materials.

12.
Hum Vaccin Immunother ; 20(1): 2371664, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-38961667

ABSTRACT

Recently, CAR-T cell therapy in hematological malignancies has received extensive attention. The objective of this study is to gain a comprehensive understanding of the current research status, development trends, research hotspots, and emerging topics pertaining to CAR-T cells in the treatment of hematological malignancies. Articles pertaining to CAR-T cell therapy for hematological malignancies from the years 2012 to 2023 were obtained and assessed from the Web of Science Core Collection (WoSCC). A bibliometric approach was employed to conduct a scientific, comprehensive, and objective quantitative analysis, as well as a visual analysis, of this particular research domain. A comprehensive analysis was conducted on a corpus of 3643 articles, which were collaboratively authored by 72 countries and various research institutions. CAR-T cell research in treating hematological malignancies shows an increasing trend each year. Notably, the study identified the countries and institutions displaying the highest level of activity, the journals with the most citations and output, as well as the authors who garnered the highest frequency of citations and co-citations. Furthermore, the analysis successfully identified the research hotspots and highlighted six emerging topics within this domain. This study conducted a comprehensive exploration and analysis of the research status, development trends, research hotspots, and emerging topics about CAR-T cells in the treatment of hematological malignancies from 2012 to 2023. The findings of this study will serve as a valuable reference and guide for researchers seeking to delve deeper into this field and determine the future direction of their research.


Subject(s)
Bibliometrics , Hematologic Neoplasms , Immunotherapy, Adoptive , Hematologic Neoplasms/therapy , Humans , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen/immunology
13.
BMJ Open Ophthalmol ; 9(1)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38969362

ABSTRACT

OBJECTIVES: This study aimed to quantitatively evaluate optic nerve head and retinal vascular parameters in children with hyperopia in relation to age and spherical equivalent refraction (SER) using artificial intelligence (AI)-based analysis of colour fundus photographs (CFP). METHODS AND ANALYSIS: This cross-sectional study included 324 children with hyperopia aged 3-12 years. Participants were divided into low hyperopia (SER+0.5 D to+2.0 D) and moderate-to-high hyperopia (SER≥+2.0 D) groups. Fundus parameters, such as optic disc area and mean vessel diameter, were automatically and quantitatively detected using AI. Significant variables (p<0.05) in the univariate analysis were included in a stepwise multiple linear regression. RESULTS: Overall, 324 children were included, 172 with low and 152 with moderate-to-high hyperopia. The median optic disc area and vessel diameter were 1.42 mm2 and 65.09 µm, respectively. Children with high hyperopia had larger superior neuroretinal rim (NRR) width and larger vessel diameter than those with low and moderate hyperopia. In the univariate analysis, axial length was significantly associated with smaller superior NRR width (ß=-3.030, p<0.001), smaller temporal NRR width (ß=-1.469, p=0.020) and smaller vessel diameter (ß=-0.076, p<0.001). A mild inverse correlation was observed between the optic disc area and vertical disc diameter with age. CONCLUSION: AI-based CFP analysis showed that children with high hyperopia had larger mean vessel diameter but smaller vertical cup-to-disc ratio than those with low hyperopia. This suggests that AI can provide quantitative data on fundus parameters in children with hyperopia.


Subject(s)
Artificial Intelligence , Hyperopia , Optic Disk , Photography , Retinal Vessels , Humans , Hyperopia/diagnosis , Hyperopia/physiopathology , Cross-Sectional Studies , Male , Child , Female , Child, Preschool , Optic Disk/diagnostic imaging , Optic Disk/pathology , Optic Disk/blood supply , Retinal Vessels/diagnostic imaging , Retinal Vessels/pathology , Photography/methods , Fundus Oculi , Visual Acuity/physiology , Refraction, Ocular/physiology
14.
Chemistry ; : e202401487, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38963680

ABSTRACT

Vitamin D deficiency affects nearly half the population, with many requiring or opting for supplements with vitamin D3(VD3), the precursor of vitamin D (1α,25-dihydroxyVD3). 25-HydroxyVD3, the circulating form of vitamin D, is a more effective supplement than VD3 but its synthesis is complex. We report here the engineering of cytochrome P450BM3(CYP102A1) for the selective oxidation of VD3 to 25-hydroxyVD3. Long-range effects of the substrate-channel mutation Glu435Ile promoted binding of the VD3 side chain close to the heme, enhancing VD3 oxidation activity that reached 6.62 g of 25-hydroxyVD3 isolated from a 1-litre scale reaction (69.1% yield; space-time-yield 331 mg/L/h).

15.
Cell Biosci ; 14(1): 88, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956702

ABSTRACT

This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer's Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4's role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aß and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.

16.
J Gynecol Oncol ; 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38991946

ABSTRACT

OBJECTIVE: To analyze the fluctuations of patient-reported outcomes (PROs) and their relationships with cytokines in the peripheral blood of patients undergoing chemotherapy for ovarian cancer (OC). METHODS: PROs burden was prospectively measured by the M.D. Anderson Symptom Inventory-Ovarian Cancer (MDASI-OC) at baseline before chemotherapy, on a daily basis during and post-chemotherapy days (PCD) 7, 14, and 20. Cytokines were collected at baseline, days prior to hospital discharge and PCD 20. Pearson correlation was used to explore the associations between PROs and cytokines levels in peripheral blood. RESULTS: The top 8 rated symptoms were compared between the neoadjuvant chemotherapy (NACT) group (n=20) and the postoperative adjuvant chemotherapy (PAC) group (n=7). Before chemotherapy, the mean scores of fatigue and lack of appetite in the NACT group were higher than those in the PAC group. After chemotherapy, pain, nausea, vomiting, disturbed sleep, lack of appetite, and constipation increased to peak during PCD 2-6; while, fatigue and numbness or tingling remained at high levels over PCD 2-13. By PCD 20, disturbed sleep and fatigue showed a significant increase in mean scores, particularly in the NACT group; while, other symptom scores decreased and returned to baseline levels. Additionally, the longitudinal fluctuations in pain, fatigue, and lack of appetite were positively associated with circulating levels of interleukin-6 and interferon gamma (p<0.05). CONCLUSION: MDASI-OC was feasible and adaptable for demonstrating the fluctuations of symptom burden throughout chemotherapy course. Moreover, symptoms changing along with cytokines levels could provide clues for exploring mechanism underlying biochemical etiology.

17.
Huan Jing Ke Xue ; 45(7): 4164-4176, 2024 Jul 08.
Article in Chinese | MEDLINE | ID: mdl-39022963

ABSTRACT

Studying the response relationship and spatial distribution characteristics of carbon reserve and land use change and predicting the change trend of carbon reserve caused by the change of land use type in the future can provide some reference for watershed policy formulation, land use structure adjustment, and the realization of the "two-carbon" goal. Based on the land use data from 2000, 2010, and 2020, the InVEST model was used to calculate carbon reserves and analyze the change characteristics and to simulate the land use change and its impact on carbon reserves in natural development, urban development, and ecological protection in 2030 with the help of the PLUS model. The study found that ① the main land types in the Shiyang River Basin from 2000 to 2020 were cultivated land, grassland, and unused land. The area of cultivated land, water area, and construction land in the Shiyang River Basin showed a significant increasing trend, and the construction land area increased the most. ② In the natural development scenario of 2030, cultivated land, water area, and construction all increased by 6.15%, 9.56%, and 29.9%, respectively. In the urban development scenario, the area of construction land increased the most. Compared with that in the other two scenarios, the area of forest land and grassland increased in the ecological protection scenarios. ③ The carbon reserves of the Shiyang River Basin from 2000 to 2020 showed a steady increase, with an overall increase of 0.035×108 t. The increased carbon reserves were mainly due to the increase in cultivated land area. ④ In 2030, the carbon reserves of the Shiyang River Basin showed an increasing trend in all three scenarios. The carbon reserves in the three scenarios were 5.65×108, 5.64×108,and 5.73×108 t, respectively, with the largest increase in carbon reserves in the ecological conservation scenario, mainly due to the increase in grassland and woodland. The results showed that the expansion of construction land was the main cause of the loss of carbon reserves. If effective ecological protection measures are taken, the carbon reserves in the Shiyang River Basin will be improved, and the problem of the loss of carbon reserves caused by economic development can be solved.

18.
Kaohsiung J Med Sci ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39023189

ABSTRACT

The human gut microbiota significantly impacts health, including liver conditions like liver cirrhosis (LC) and spontaneous bacterial peritonitis (SBP). Immunoglobulin A (IgA) plays a central role in maintaining gut microbial balance. Understanding IgA's interplay with gut microbiota and liver health is crucial. This study explores the relationship between fecal IgA levels, gut microbiota, and liver injury severity. A total of 69 LC patients and 30 healthy controls were studied. Fecal IgA levels were measured using ELISA, and IgA-coated bacteria were quantified via flow cytometry. Microbiota diversity and composition were assessed through 16S rRNA sequencing. Liver injury severity was graded using the Child-Pugh score. Statistical analyses determined correlations. LC patients had higher fecal IgA levels than controls, correlating positively with liver injury severity. Microbiota diversity decreased with severity, accompanied by shifts in composition favoring pro-inflammatory species. Ralstonia abundance positively correlated with liver injury, whereas Faecalibacterium showed a negative correlation. Specific microbial markers for SBP were identified. Functional profiling revealed altered microbial functionalities in LC and SBP. Elevated fecal IgA levels, coupled with microbiota alterations, correlate with liver injury severity in LC patients. Modulating gut microbiota could be a promising strategy for managing liver-related conditions. Further research is needed to understand underlying mechanisms and translate findings into clinical practice, potentially improving patient outcomes.

19.
Article in English | MEDLINE | ID: mdl-39016521

ABSTRACT

Phenotypic drug discovery (PDD), which involves harnessing biological systems directly to uncover effective drugs, has undergone a resurgence in recent years. The rapid advancement of artificial intelligence (AI) over the past few years presents numerous opportunities for augmenting phenotypic drug screening on microfluidic platforms, leveraging its predictive capabilities, data analysis, efficient data processing, etc. Microfluidics coupled with AI is poised to revolutionize the landscape of phenotypic drug discovery. By integrating advanced microfluidic platforms with AI algorithms, researchers can rapidly screen large libraries of compounds, identify novel drug candidates, and elucidate complex biological pathways with unprecedented speed and efficiency. This review provides an overview of recent advances and challenges in AI-based microfluidics and their applications in drug discovery. We discuss the synergistic combination of microfluidic systems for high-throughput screening and AI-driven analysis for phenotype characterization, drug-target interactions, and predictive modeling. In addition, we highlight the potential of AI-powered microfluidics to achieve an automated drug screening system. Overall, AI-powered microfluidics represents a promising approach to shaping the future of phenotypic drug discovery by enabling rapid, cost-effective, and accurate identification of therapeutically relevant compounds.

20.
Nat Commun ; 15(1): 5949, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39009587

ABSTRACT

Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand-receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP. Notably, fibroblasts and DCs expressing IL13RA1 respond to IL13-secreting Th2 cells, thereby amplifying Th2 cell-mediated cascade responses, which occurs through the specific upregulation of PLA2G2A in fibroblasts and CCL17 in myeloid cells, creating a positive feedback loop integral to immune-stromal crosstalk. Furthermore, PLA2G2A and CCL17 contribute to an increased titer of pathogenic anti-BP180-NC16A autoantibodies in BP patients. Our work provides a comprehensive insight into BP pathogenesis and shows a mechanism governing immune-stromal interactions, providing potential avenues for future therapeutic research.


Subject(s)
Chemokine CCL17 , Dendritic Cells , Fibroblasts , Pemphigoid, Bullous , Single-Cell Analysis , Th2 Cells , Humans , Pemphigoid, Bullous/immunology , Pemphigoid, Bullous/genetics , Single-Cell Analysis/methods , Fibroblasts/metabolism , Fibroblasts/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , Chemokine CCL17/genetics , Chemokine CCL17/metabolism , Th2 Cells/immunology , Autoantibodies/immunology , Transcriptome , Interleukin-13/metabolism , Interleukin-13/genetics , Interleukin-13/immunology , Non-Fibrillar Collagens/immunology , Non-Fibrillar Collagens/genetics , Non-Fibrillar Collagens/metabolism , Inflammation/immunology , Inflammation/genetics , Inflammation/metabolism , Gene Expression Profiling/methods , Male , Female , Autoantigens/immunology , Autoantigens/metabolism , Autoantigens/genetics , Collagen Type XVII , Myeloid Cells/metabolism , Myeloid Cells/immunology , Stromal Cells/metabolism , Stromal Cells/immunology
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