Dose-response relationship between body mass index and hypertension: A cross-sectional study from Eastern China.

Background: A high body mass index (BMI) increases the risk of hypertension. However, little is known about the dose-dependent association between BMI and hypertension. Therefore, this study investigated the prevalence of hypertension in 7568 subjects from the Jiangsu Province, Eastern China, and analyzed the dose-response relationship between BMI and hypertension risk. Methods: The eligible subjects completed a structured questionnaire and clinical biochemical indicators were measured according to standardized protocols. Multivariate logistic regression models were used to evaluate the association between BMI and hypertension. Restricted cubic spline (RCS) analysis was used to analyze the dose-response relationship between BMI and hypertension risk. Moreover, sensitivity analysis was performed to verify the robustness of our findings. Results: The prevalence of hypertension was 35.3 % in the total population. BMI was significantly associated with systolic and diastolic blood pressure. The fully-adjusted odds ratio (OR) with 95 % confidence interval (CI) for hypertension was 1.17 (1.15, 1.19) for every 1 kg/m2 increase in BMI. Furthermore, the OR (95 % CI) for hypertension in the highest BMI group (Obesity) was 4.14 (3.45, 4.96) after adjusting for covariates compared with the normal group. Multivariable adjusted RCS analysis showed a positive and linear dose-response relationship between BMI and hypertension risk both in male and female populations (all P for non-linearity > 0.05). Conclusion: Our study demonstrated a positive and linear dose-response relationship between BMI and the risk of hypertension. The results of this study provide evidence for BMI-related clinical interventions to reduce the risk of hypertension.

Mechanocatalytic Hydrogen Generation in Centrosymmetric Barium Dititanate.

Novel phase of nano materials that break the traditional structural constraints are highly desirable, particularly in the field of mechanocatalysis, offering versatile applications ranging from energy to medical diagnosis and treatment. In this work, a distinct layered barium dititanate (BaTi2O5) nanocrystals using a pH-modulated hydrothermal method is successfully synthesized. These nanocrystals exhibit outstanding hydrogen generation capability (1160 µmol g-1 h-1 in pure water) and demonstrate remarkable performance in organic dye degradation using ultrasonication. The crystal structure of this newly discovered BaTi2O5 phase, is determined by a combination of synchrotron Powder Diffraction refinement and X-ray adsorption techniques, including X-ray Absorption Near Edge Structure (XANES) and Extended X-ray Absorption Fine Structure (EXAFS). Density Functional Theory calculations revealed that the newly-discovered BaTi2O5 phase demonstrates dipole moments along the z-axis, distributed in an antiparallel direction within a single unit cell. These inherent dipoles induce a surface polarization and a ferroelectric-flexoelectric response under mechanical stimuli when the materials go to nano dimension. With a band alignment well-suitable for hydrogen and reactive oxygen species generation, this BaTi2O5 phase demonstrates promising potential for Mechanocatalysis. The discovery of this distinct phase not only enriches the material candidates for mechanocatalysis but also provides valuable insights.

Research Status of Lignin-Based Polyurethane and Its Application in Flexible Electronics.

Polyurethanes (PU) have drawn great attention due to their excellent mechanical properties and self-healing and recyclable abilities. Lignin is a natural and renewable raw material in nature, composed of a large number of hydroxyl groups, and has a great potential to replace petroleum polyols in PU synthesis. This review summarizes the recent advances in modification methods such as the liquefaction, alkylation, and demethylation of lignin, and a systematic analysis of how to improve the reactivity and monomer substitution of lignin during polyurethane synthesis for the green manufacturing of high-performance polyurethanes was conducted. Polyurethane can be used in the form of films, foams, and elastomers instead of conventional materials as a dielectric or substrate material to improve the reliability and durability of flexible sensors; this review summarizes the green synthesis of polyurethanes and their applications in flexible electronics, which are expected to provide inspiration for the wearable electronics sector.

FTO promotes gefitinib-resistance by enhancing PELI3 expression and autophagy in non-small cell lung cancer.

The established recognition of N6-methyladenosine (m6A) modification as an indispensable regulatory agent in human cancer is widely accepted. However, the understanding of m6A's role and the mechanisms underlying its contribution to gefitinib resistance is notably limited. Herein, using RT-qPCR, Western blot, Cell proliferation and apoptosis, as well as RNA m6A modification assays, we substantiated that heightened FTO (Fat Mass and Obesity-associated protein) expression substantially underpins the emergence of gefitinib resistance in NSCLC cells. This FTO-driven gefitinib resistance is hinged upon the co-occurrence of PELI3 (Pellino E3 Ubiquitin Protein Ligase Family Member 3) expression and concurrent autophagy activation. Manipulation of PELI3 expression and autophagy activation, including its attenuation, was efficacious in both inducing and overcoming gefitinib resistance within NSCLC cells, as validated in vitro and in vivo. In summary, this study has successfully elucidated the intricate interplay involving FTO-mediated m6A modification, its consequential downstream effect on PELI3, and the concurrent involvement of autophagy in fostering the emergence of gefitinib resistance within the therapeutic context of NSCLC.

Uncovering the Interaction between TRAF1 and MAVS in the RIG-I Pathway to Enhance the Upregulation of IRF1/ISG15 during Classical Swine Fever Virus Infection.

Classical swine fever (CSF) is caused by the classical swine fever virus (CSFV), which poses a threat to swine production. The activation of host innate immunity through linker proteins such as tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) is crucial for the induction of the NF-κB pathway. Recent research has revealed the involvement of mitochondrial antiviral-signaling protein (MAVS) in the interaction with TRAF2, 3, 5, and 6 to activate both the NF-κB and IRF3 pathways. This study revealed that CSFV infection led to the upregulation of TRAF1 mRNA and protein levels; moreover, TRAF1 overexpression inhibited CSFV replication, while TRAF1 knockdown promoted replication, highlighting its importance in the host response to CSFV infection. Additionally, the expression of RIG-I, MAVS, TRAF1, IRF1, and ISG15 were detected in PK-15 cells infected with CSFV, revealing that TRAF1 plays a role in regulating IRF1 and ISG15 within the RIG-I pathway. Furthermore, Co-IP, GST pull-down, and IFA analyses demonstrated that TRAF1 interacted with MAVS and co-localized in the cytoplasm during CSFV infection. Ultimately, TRAF1 acted as a novel member of the TRAF family, bound to MAVS as a linker molecule, and functioned as a mediator downstream of MAVS in the RIG-I/MAVS pathway against CSFV replication.

Acetylation model predicts prognosis of patients and affects immune microenvironment infiltration in epithelial ovarian carcinoma.

BACKGROUND: Epithelial ovarian carcinoma (EOC) is a prevalent gynaecological malignancy. The prognosis of patients with EOC is related to acetylation modifications and immune responses in the tumour microenvironment (TME). However, the relationships between acetylation-related genes, patient prognosis, and the tumour immune microenvironment (TIME) are not yet understood. Our research aims to investigate the link between acetylation and the tumour microenvironment, with the goal of identifying new biomarkers for estimating survival of patients with EOC. METHODS: Using data downloaded from the tumour genome atlas (TCGA), genotypic tissue expression (GTEx), and gene expression master table (GEO), we comprehensively evaluated acetylation-related genes in 375 ovarian cancer specimens and identified molecular subtypes using unsupervised clustering. The prognosis, TIME, stem cell index and functional concentration analysis were compared among the three groups. A risk model based on differential expression of acetylation-related genes was established through minimum absolute contraction and selection operator (LASSO) regression analysis, and the predictive validity of this feature was validated using GEO data sets. A nomogram is used to predict a patient's likelihood of survival. In addition, different EOC risk groups were evaluated for timing, tumour immune dysfunction and exclusion (TIDE) score, stemness index, somatic mutation, and drug sensitivity. RESULTS: We used the mRNA levels of the differentially expressed genes related to acetylation to classify them into three distinct clusters. Patients with increased immune cell infiltration and lower stemness scores in cluster 2 (C2) exhibited poorer prognosis. Immunity and tumourigenesis-related pathways were highly abundant in cluster 3 (C3). We developed a prognostic model for ten differentially expressed acetylation-related genes. Kaplan-Meier analysis demonstrated significantly worse overall survival (OS) in high-risk patients. Furthermore, the TIME, tumour immune dysfunction and exclusion (TIDE) score, stemness index, tumour mutation burden (TMB), immunotherapy response, and drug sensitivity all showed significant correlations with the risk scores. CONCLUSIONS: Our study demonstrated a complex regulatory mechanism of acetylation in EOC. The assessment of acetylation patterns could provide new therapeutic strategies for EOC immunotherapy to improve the prognosis of patients.

Additive-Free Construction of Tetrahydropyrimidine Skeleton by using 1,3,5-Triazinane as Four-Atom Synthon.

Herein, an unprecedented [4 + 2] cycloaddition of enaminone with 1,3,5-triazinane has been developed. The representative semihydrogenated aromatic heterocycle 1,2,3,4-tetrahydropyrimidines have been synthesized with a broad substrate scope, demonstrating potential antitumor activity. This approach has been smoothly conducted under additive-free and environmentally friendly conditions that are compatible with various functional groups. Furthermore, the condition optimization process reveals that the tetrahydropyrimidine product is regulated via the reaction temperature.

ABT­737 increases cisplatin sensitivity through the ROS­ASK1­JNK MAPK signaling axis in human ovarian cancer cisplatin­resistant A2780/DDP cells.

Ovarian cancer is a gynecological malignant tumor with the highest mortality rate, and chemotherapy resistance seriously affects patient therapeutic outcomes. It has been shown that the high expression of anti­apoptotic proteins Bcl­2 and Bcl­xL is closely related to ovarian cancer chemotherapy resistance. Therefore, reducing Bcl­2 and Bcl­xL expression levels may be essential for reversing drug resistance in ovarian cancer. ABT­737 is a BH3­only protein mimetic, which can effectively inhibit the expression of the anti­apoptotic proteins Bcl­xL and Bcl­2. Although it has been shown that ABT­737 can increase the sensitivity of ovarian cancer cells to cisplatin, the specific molecular mechanism remains unclear and requires further investigation. In the present study, the results revealed that ABT­737 can significantly increase the activation levels of JNK and ASK1 induced by cisplatin in A2780/DDP cells, which are cisplatin­resistant ovarian cancer cells. Inhibition of the JNK and ASK1 pathway could significantly reduce cisplatin cytotoxicity increased by ABT­737 in A2780/DDP cells, while inhibiting the ASK1 pathway could reduce JNK activation. In addition, it was further determined that ABT­737 could increase reactive oxygen species (ROS) levels in A2780/DDP cells induced by cisplatin. Furthermore, the inhibition of ROS could significantly reduce JNK and ASK1 activation and ABT­737­mediated increased cisplatin cytotoxicity in A2780/DDP cells. Overall, the current data identified that activation of the ROS­ASK1­JNK signaling axis plays an essential role in the ability of ABT­737 to increase cisplatin sensitivity in A2780/DDP cells. Therefore, upregulation the ROS­ASK1­JNK signaling axis is a potentially novel molecular mechanism by which ABT­737 can enhance cisplatin sensitivity of ovarian cancer cells. In addition, the present research can also provide new therapeutic strategies and new therapeutic targets for patients with cisplatin­resistant ovarian cancer with high Bcl­2/Bcl­xL expression patterns.

Frequency-dependent effects of 0.05% atropine eyedrops on myopia progression and peripheral defocus: a prospective study.

BACKGROUND: Atropine, specifically 0.05% eyedrops, has proven effective in slowing myopia progression. This study aims to investigate peripheral refraction (PR) characteristics in myopic children treated with 0.05% atropine eyedrops at different frequencies. METHODS: One hundred thirty-eight myopic children completed this one-year prospective study, randomly assigned to once daily (7/7), twice per week (2/7), or once per week (1/7) groups. Spherical equivalent (SE) and axial length (AL) were measured. PR was assessed using a custom-made Hartmann-Shack wavefront peripheral sensor, covering a visual field of horizontal 60° and vertical 36°. Relative peripheral refraction (RPR) was calculated by subtracting central from peripheral measurements. RESULTS: After one year, SE increased more significantly in the 1/7 group compared to the 7/7 group (P < 0.001) and 2/7 group (P = 0.004); AL elongation was also greater in the 1/7 group compared to the 7/7 group (P < 0.001). In comparison with higher frequency groups, 1/7 group exhibited more myopic PR in the fovea and its vertical superior, inferior, and nasal retina; and less myopic RPR in the periphery retina after one-year (P < 0.05). Additionally, RPR in the 7/7 group demonstrated myopic shift across the entire retina, the 2/7 group in temporal and inferior retina, while the 1/7 group showed a hyperopic shift in the superior retina (P < 0.05). Moreover, myopic shift of RPR in the temporal retina is related to less myopia progression, notably in the 7/7 group (P < 0.05). CONCLUSIONS: Atropine inhibits myopia progression in a frequency-dependent manner. The once-daily group showed the slowest myopia progression but exhibited more myopic shifts in RPR. Additionally, RPR in the temporal retina was related to myopia progression in all groups. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2100043506. Registered 21 February 2021, https://www.chictr.org.cn/showproj.html?proj=122214.

Puerarin inhibits HDAC1-induced oxidative stress disorder by activating JNK pathway and alleviates acrolein-induced atherosclerosis.

OBJECTIVE: Atherosclerosis (AS) is a common pathogenesis of cardiovascular diseases. Puerarin (Pue) is a Chinese herbal remedy used to prevent and treat AS. Here, this research investigated the effect of Pue on AS progression. METHODS: ApoE-/- mice were induced with acrolein. Body weight, blood lipid index, inflammatory factors, mitochondrial oxidative stress, and lipid deposition were detected. IL-6 and TNF-α were detected by ELISA. Oil red staining and H&E staining were used to observe the aortic sinus plaque lesions. Serum expressions of inflammatory factors IL-6, TNF-a, SOD, GSH and MDA were detected by ELISA, the mRNA expression levels of HDAC1 in the aorta were detected by RT-qPCR, and IL-6 and TNF-α in the aorta were detected by immunohistochemistry. JNK, p-JNK, OPA-1, and HDAC1 were detected by Western blotting. RESULTS: Pue administration can effectively reduce lipid accumulation in AS mice induced by acrolein. Pue promoted the activity of SOD, GSH and MDA, and inhibited the formation of atherosclerotic plaques and the process of aortic histological changes. Pue reduced IL-6 and TNF-α. HDAC1 expression was down-regulated and p-JNK-1 and JNK protein expression was up-regulated. CONCLUSION: Pue reduces inflammation and alleviates AS induced by acrolein by mediating the JNK pathway to inhibit HDAC1-mediated oxidative stress disorder.

Rabies Virus Infection Causes Pyroptosis of Neuronal Cells.

Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin-eosin staining, transmission electron microscopy, transcriptomics analysis, and immune response factor testing to investigate RABV-infected neurons. We successfully isolated the neurons from murine brains. The specificity of the isolated neurons was identified by a monoclonal antibody, and the viability of the neurons was 83.53-95.0%. We confirmed that RABV infection induced serious damage to the neurons according to histochemistry and transmission electron microscope (TEM) scanning. In addition, the transcriptomics analysis suggested that multiple genes related to the pyroptosis pathway were significantly upregulated, including gasdermin D (Gsdmd), Nlrp3, caspase-1, and IL-1ß, as well as the chemokine genes Ccl2, Ccl3, Ccl4, Ccl5, Ccl7, Ccl12, and Cxcl10. We next verified this finding in the brains of mice infected with the rRC-HL, GX074, and challenge virus standard strain-24 (CVS-24) strains of RABV. Importantly, we found that the expression level of the Gsdmd protein was significantly upregulated in the neurons infected with different RABV strains and ranged from 691.1 to 5764.96 pg/mL, while the basal level of mock-infected neurons was less than 100 pg/mL. Taken together, our findings suggest that Gsdmd-induced pyroptosis is involved in the neuron damage caused by RABV infection.

Transforming growth factor-ß1 protects mechanically injured cortical murine neurons by reducing trauma-induced autophagy and apoptosis.

Transforming growth factor ß1 (TGF-ß1) has a neuroprotective function in traumatic brain injury (TBI) through its anti-inflammatory and immunomodulatory properties. However, the precise mechanisms underlying the neuroprotective actions of TGF-ß1 on the cortex require further investigation. In this study, we were aimed to investigate the regulatory function of TGF-ß1 on neuronal autophagy and apoptosis using an in vitro primary cortical neuron trauma-injury model. LDH activity was assayed to measure cell viability, and intracellular [Ca2+] was measured using Fluo-4-AM in an in vitro primary cortical neuron trauma-injury model. RNA-sequencing (RNAseq), immunofluorescent staining, transmission electron microscopy (TEM), western blot and CTSD activity detection were employed. We observed significant enrichment of DEGs related to autophagy, apoptosis, and the lysosome pathway in trauma-injured cortical neurons. TEM confirmed the presence of autophagosomes as well as autophagolysosomes. Western blot revealed upregulation of autophagy-related protein light chain 3 (LC3-II/LC3-I), sequestosome 1 (SQSTM1/p62), along with apoptosis-related protein cleaved-caspase 3 in trauma-injured primary cortical neurons. Furthermore, trauma-injured cortical neurons showed an upregulation of lysosomal marker protein (LAMP1) and lysosomal enzyme mature cathepsin D (mCTSD), but a decrease in the activity of CTSD enzyme. These results indicated that apoptosis was up-regulated in trauma- injured cortical neurons at 24 h, accompanied by lysosomal dysfunction and impaired autophagic flux. Notably, TGF-ß1 significantly reversed these changes. Our results suggested that TGF-ß1 exerted neuroprotective effects on trauma- injured cortical neurons by reducing lysosomal dysfunction, decreasing the accumulation of autophagosomes and autophagolysosomes, and enhancing autophagic flux.

Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II clinical trial.

OBJECTIVE: To evaluate the feasibility, safety and efficacy of concurrent simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with nimotuzumab in the treatment of locally advanced esophageal squamous cell cancer (ESCC). METHODS: Eligible patients were histologically proven to have locally advanced ESCC, and were unable to tolerate or refuse concurrent chemoradiotherapy (CCRT). Enrolled patients underwent concurrent SIB-IMRT in combination with nimotuzumab. SIB-IMRT: For the planning target volume of clinical target volume (PTV-C), the prescription dose was 50.4 Gy/28fractions, 1.8 Gy/fraction, 5fractions/week, concurrently, the planning target volume of gross tumor (PTV-G) undergone an integrated boost therapy, with a prescription dose of 63 Gy/28fractions, 2.25 Gy/fraction, 5 fractions/week. Nimotuzumab was administered concurrently with radiotherapy, 200 mg/time, on D1, 8, 15, 22, 29, and 36, with a total accumulation of 1200 mg through intravenous infusion. The primary endpoint of the study was the safety and efficacy of the combined treatment regimen, and the secondary endpoints were 1-year, 2-year, and 3-year local control and survival outcomes. RESULTS: (1) From December 2018 to August 2021, 35 patients with stage II-IVA ESCC were enrolled and 34 patients completed the full course of radiotherapy and the intravenous infusion of full-dose nimotuzumab. The overall completion rate of the protocol was 97.1%. (2) No grade 4-5 adverse events occurred in the entire group. The most common treatment-related toxicity was acute radiation esophagitis, with a total incidence of 68.6% (24/35). The incidence of grade 2 and 3 acute esophagitis was 25.7% (9/35) and 17.1% (6/35), respectively. The incidence of acute radiation pneumonitis was 8.6% (3/35), including one case each of Grades 1, 2, and 3 pneumonitis. Adverse events in other systems included decreased blood cells, hypoalbuminemia, electrolyte disturbances, and skin rash. Among these patients, five experienced grade 3 electrolyte disturbances during the treatment period (three with grade 3 hyponatremia and two with grade 3 hypokalemia). (3) Efficacy: The overall CR rate was 22.8%, PR rate was 71.4%, ORR rate was 94.2%, and DCR rate was 97.1%.(4) Local control and survival: The 1-, 2-, and 3-year local control (LC) rate, progression-free survival(PFS) rate, and overall survival(OS) rate for the entire group were 85.5%, 75.4%, and 64.9%; 65.7%, 54.1%, and 49.6%; and 77.1%, 62.9%, and 54.5%, respectively. CONCLUSIONS: The combination of SIB-IMRT and nimotuzumab for locally advanced esophageal cancer demonstrated good feasibility, safety and efficacy. It offered potential benefits in local control and survival. Acute radiation esophagitis was the primary treatment-related toxicity, which is clinically manageable. This comprehensive treatment approach is worthy of further clinical exploration (ChiCTR1900027936).

Magnetic Field-induced Disordered Phase of Spinel Oxides for High Battery Performance.

The disordered phase of spinel LiMn1.5Ni0.5O4 (LNMO) is more appealing as high-voltage cathode due to its superior electrochemical performance compared to its ordered counterpart. Various methods are developed to induce a phase transition. However, the resulting materials often suffer from capacity degradation due to the adverse influence of accompanying Mn3+ ions. This study presents the utilization of local magnetic fields generated by a magnetic Fe3O4 shell to induce a disordered phase transition in LNMO at lower temperature, transitioning it from an order state without significantly increasing the Mn3+ content. The pivotal role played by the local magnetic fields is evidenced through comparisons with samples with nonmagnetic Al2O3 shell, samples subjected to sole heat treatment, and samples heat-treated within magnetic fields. The key finding is that magnetic fields can initiate a radical pair mechanism, enabling the induction of order-disorder phase transition even at lower temperatures. The disordered spinal LNMO with a magnetic Fe3O4 shell exhibits excellent cycling stability and kinetic properties in electrochemical characterization as a result. This innovation not only unravels the intricate interplay between the disordered phase and Mn3+ content in the cathode spinel but also pioneers the use of magnetic field effects for manipulating material phases.

The efficacy and safety of neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer patients: a systematic review.

Background: Several studies have explored the effectiveness of PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy (nCRT) in the treatment of locally advanced rectal cancer(LARC), particularly in microsatellite stable(MSS) or mismatch repair proficient(pMMR) LARC patients. We undertook a single-arm systematic review to comprehensively evaluate the advantages and potential risks associated with the use of PD-1/PD-L1 inhibitors in conjunction with nCRT for patients diagnosed with locally advanced rectal cancer. Methods: The PubMed, Embase, Cochrane Library, ClinicalTrials.gov, ASCO and ESMO were searched for related studies. The main outcomes were pathologic complete response (pCR), major pathological response (MPR), anal preservation, and adverse effects (AEs). Results: Fourteen articles including 533 locally advanced rectal cancer (LARC) patients were analyzed. The pooled pCR, MPR, and anal preservation rates were 36%, 66% and 86%. Grade ≥3 adverse events occurred in 20%. Subgroup analysis showed that; dMMR/MSI-H had a pooled pCR (100%) and MPR (100%), pMMR/MSS had a pooled pCR (38%) and MPR (60%); the short-course radiotherapy and long-course radiotherapy had pooled pCR rates of 51% and 30%, respectively. The rates of pCR for the concurrent and sequential immuno-chemoradiotherapy subgroups at 30% and 40%, mirroring pCR rates for the PD-L1 and PD-1 inhibitor subgroups were 32% and 40%, respectively. Conclusion: In cases of locally advanced rectal cancer, PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy have shown promising response rates and acceptable toxicity profiles. PD-1/PD-L1 inhibitors combined with neoadjuvant chemoradiotherapy hence has a positive outcome even in MSS LARC patients. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/#myprospero, identifier CRD42023465380.

Mitigation of Oxidative Stress in Idiopathic Pulmonary Fibrosis Through Exosome-Mediated Therapies.

Idiopathic pulmonary fibrosis (IPF) poses a formidable clinical challenge, characterized by the thickening of alveolar septa and the onset of pulmonary fibrosis. The pronounced activation of oxidative stress emerges as a pivotal hallmark of inflammation. Traditional application of exogenous antioxidants proves inadequate in addressing oxidative stress, necessitating exploration into strategies to augment their antioxidant efficacy. Exosomes, nano-sized extracellular vesicles harboring a diverse array of bioactive factors, present as promising carriers with the potential to meet this challenge. Recent attention has been directed towards the clinical applications of exosomes in IPF, fueling the impetus for this comprehensive review. We have compiled fresh insights into the role of exosomes in modulating oxidative stress in IPF and delved into their potential as carriers for regulating endogenous reactive oxygen species generation. This review endeavors to bridge the divide between exosome research and IPF, traversing from bedside to bench. Through the synthesis of recent findings, we propose exosomes as a novel and promising strategy for improving the outcomes of IPF therapy.

Apolipoprotein D facilitates rabies virus propagation by interacting with G protein and upregulating cholesterol.

Rabies virus (RABV) causes a fatal neurological disease, consisting of unsegmented negative-strand RNA, which encodes five structural proteins (3'-N-P-M-G-L-5'). Apolipoprotein D (ApoD), a lipocalin, is upregulated in the nervous system after injury or pathological changes. Few studies have focused on the role of ApoD during virus infection so far. This study demonstrated that ApoD is upregulated in the mouse brain (in vivo) and C8-D1A cells (in vitro) after RABV infection. By upregulating ApoD expression in C8-D1A cells, we found that ApoD facilitated RABV replication. Additionally, Co-immunoprecipitation demonstrated that ApoD interacted with RABV glycoprotein (G protein). The interaction could promote RABV replication by upregulating the cholesterol level. These findings revealed a novel role of ApoD in promoting RABV replication and provided a potential therapeutic target for rabies.

Artificial Intelligence-Assisted Prescription Determination for Orthokeratology Lens Fitting: From Algorithm to Clinical Practice.

OBJECTIVES: To explore the potential of artificial intelligence (AI) to assist prescription determination for orthokeratology (OK) lenses. METHODS: Artificial intelligence algorithm development followed by a real-world trial. A total of 11,502 OK lenses fitting records collected from seven clinical environments covering major brands. Records were randomly divided in a three-way data split. Cross-validation was used to identify the most accurate algorithm, followed by an evaluation using an independent test data set. An online AI-assisted system was implemented and assessed in a real-world trial involving four junior and three senior clinicians. RESULTS: The primary outcome measure was the algorithm's accuracy (ACC). The ACC of the best performance of algorithms to predict the targeted reduction amplitude, lens diameter, and alignment curve of the prescription was 0.80, 0.82, and 0.83, respectively. With the assistance of the AI system, the number of trials required to determine the final prescription significantly decreased for six of the seven participating clinicians (all P <0.01). This reduction was more significant among junior clinicians compared with consultants (0.76±0.60 vs. 0.32±0.60, P <0.001). Junior clinicians achieved clinical outcomes comparable to their seniors, as 93.96% (140/149) and 94.44% (119/126), respectively, of the eyes fitted achieved unaided visual acuity no worse than 0.8 ( P =0.864). CONCLUSIONS: AI can improve prescription efficiency and reduce discrepancies in clinical outcomes among clinicians with differing levels of experience. Embedment of AI in practice should ultimately help lessen the medical burden and improve service quality for myopia boom emerging worldwide.

Elevated Water Oxidation by Cation Leaching Enabled Tunable Surface Reconstruction.

Water electrolysis is one promising and eco-friendly technique for energy storage, yet its overall efficiency is hindered by the sluggish kinetics of oxygen evolution reaction (OER). Therefore, developing strategies to boost OER catalyst performance is crucial. With the advances in characterization techniques, an extensive phenomenon of surface structure evolution into an active amorphous layer was uncovered. Surface reconstruction in a controlled fashion was then proposed as an emerging strategy to elevate water oxidation efficiency. In this work, Cr substitution induces the reconstruction of NiFexCr2-xO4 during cyclic voltammetry (CV) conditioning by Cr leaching, which leads to a superior OER performance. The best-performed NiFe0.25Cr1.75O4 shows a ~1500 % current density promotion at overpotential η=300 mV, which outperforms many advanced NiFe-based OER catalysts. It is also found that their OER activities are mainly determined by Ni : Fe ratio rather than considering the contribution of Cr. Meanwhile, the turnover frequency (TOF) values based on redox peak and total mass were obtained and analysed, and their possible limitations in the case of NiFexCr2-xO4 are discussed. Additionally, the high activity and durability were further verified in a membrane electrode assembly (MEA) cell, highlighting its potential for practical large-scale and sustainable hydrogen gas generation.