Agreements between GLIM using left calf circumference as criterion for reduced muscle mass and PG-SGA, and GLIM using ASMI for the diagnosis of malnutrition in gastric cancer patients.

OBJECTIVE: this study aimed to explore the agreements between the Global Leadership Initiative on Malnutrition (GLIM) using left calf circumference (CC) as criterion for reduced muscle mass and the Patient-Generated Subjective Global Assessment (PG-SGA), or GLIM using appendicular skeletal muscle index (ASMI) for the diagnosis of malnutrition in gastric cancer patients. METHODS: the Nutritional Risk Screening 2002 (NRS 2002) was used as nutritional risk screening. PG-SGA and GLIM were applied for malnutrition diagnosis. Agreements were evaluated by Kappa, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC). RESULTS: a total of 405 gastric cancer patients were included. The values of Kappa, sensitivity, specificity, PPV, NPV, accuracy and AUC were 0.463, 67.9 %, 87.3 %, 92.9 %, 52.8 %, 73.6 % and 0.776, and 0.496, 76.7 %, 78.0 %, 89.4 %, 57.9 %, 77.0 % and 0.773, respectively, between GLIM using CC with or without NRS 2002 and PG-SGA. All values of agreement were higher than 0.800 or 80.0 % between GLIM using left CC and GLIM using ASMI. CONCLUSION: the agreements were both acceptable between GLIM using left CC and PG-SGA, and GLIM using ASMI. Left calf circumference can be one of the credible references indicating a reduced muscle mass in patients with gastric cancer.

DOMAS: a data management software framework for advanced light sources.

In recent years, China's advanced light sources have entered a period of rapid construction and development. As modern X-ray detectors and data acquisition technologies advance, these facilities are expected to generate massive volumes of data annually, presenting significant challenges in data management and utilization. These challenges encompass data storage, metadata handling, data transfer and user data access. In response, the Data Organization Management Access Software (DOMAS) has been designed as a framework to address these issues. DOMAS encapsulates four fundamental modules of data management software, including metadata catalogue, metadata acquisition, data transfer and data service. For light source facilities, building a data management system only requires parameter configuration and minimal code development within DOMAS. This paper firstly discusses the development of advanced light sources in China and the associated demands and challenges in data management, prompting a reconsideration of data management software framework design. It then outlines the architecture of the framework, detailing its components and functions. Lastly, it highlights the application progress and effectiveness of DOMAS when deployed for the High Energy Photon Source (HEPS) and Beijing Synchrotron Radiation Facility (BSRF).

Study of the factors related to air-bone gap in enlarged vestibular aqueduct.

BACKGROUND: Over half of patients with enlarged vestibular aqueducts (EVA) will have an air-bonr gap (ABG), however, current research on audiology has focused on the influencing factors of air-conducted. OBJECTIVE: To retrospectively analyse the influencing factors and clinical manifestations of the bone-conduction threshold and ABG in patients with EVA. MATERIALS AND METHODS: We included 286 patients with EVA; among them, 126 had full SLC26A4 gene sequence results. We performed a descriptive analysis of the bone-conduction threshold and explored the effect of age. Finally, we analyzed the relationship of ABG and SLC26A4 genes with the degree of vestibular aqueduct (VA) enlargement. RESULTS: Among 555 ears, 312 (57.8%) ears had ABG; approximately 94% of the patients' bone-conduction hearing is almost completely lost at frequencies of 2 and 4 kHz. There was no linear correlation between age and bone-conduction threshold (p > 0.05). ABG did not significantly differ according to the degree of VA enlargement and number of SLC26A4 allele mutations (p > 0.05). CONCLUSIONS AND SIGNIFICANCE: Among patients with EVA, ABG is mainly produced at low frequencies and is not significantly correlated with age, size of the VA opening or SLC26A4 genes, which could be attributed to the biomechanical effects.

An improved approach of totally visceral sac separation (TVS) for incisional hernia compared with laparoscopic intraperitoneal onlay mesh plus repair (IPOM plus).

Endoscopic techniques have been widely used in ventral hernia surgery. Totally visceral sac separation (TVS) is a new concept proposed for hernia repair in recent years. The aim of this study was to contrast the postoperative results of TVS with the widely used method of Laparoscopic intraperitoneal onlay mesh plus repair (IPOM plus) for incisional hernias. The retrospective comparison analysis of 38 IPOM plus and 34 TVS was conducted during the time period between December 2019 and June 2022. For both two groups, baseline characteristics, surgical records, postoperative information, and quality of life outcomes utilizing the Carolina's Comfort Scale were collected and analyzed. There were no differences between the methods of TVS and IPOM plus among the baseline characteristics. It showed the operative time in TVS group with the mean time of 213.4 min was significantly longer than that in IPOM plus group with the mean time of 182.9 min (P = 0.010). The postoperative length of stay in TVS group was 6.2 days, which was significantly shorter than IPOM plus group with the mean time of 4.8 days (P = 0.011). The medical expenses was significantly smaller in TVS group than that in IPOM plus group (P < 0.001). The quality of life scores of TVS were significant better than IPOM plus at one week, one month and six months. Besides, both TVS and IPOM plus have very few complications. TVS approach for incisional hernias is secure, effective, and valuable. It has shorter postoperative length of stay, higher quality of life, longer operative time, smaller medical expenses, and approximate complications compared with IPOM plus procedure. Our results have a greater contribution to the application and popularization of TVS technique.

Photocycle alteration and increased enzymatic activity in genetically modified photoactivated adenylate cyclase OaPAC.

Photoactivated adenylate cyclases (PACs) are light activated enzymes that combine blue light sensing capacity with the ability to convert ATP to cAMP and pyrophosphate (PPi) in a light-dependent manner. In most of the known PACs blue light regulation is provided by a blue light sensing domain using flavin which undergoes a structural reorganization after blue-light absorption. This minor structural change then is translated toward the C-terminal of the protein, inducing a larger conformational change that results in the ATP conversion to cAMP. As cAMP is a key second messenger in numerous signal transduction pathways regulating various cellular functions, PACs are of great interest in optogenetic studies. The optimal optogenetic device must be "silent" in the dark and highly responsive upon light illumination. PAC from Oscillatoria acuminata is a very good candidate as its basal activity is very small in the dark and the conversion rates increase 20-fold upon light illumination. We studied the effect of replacing D67 to N, in the blue light using flavin domain. This mutation was found to accelerate the primary electron transfer process in the photosensing domain of the protein, as has been predicted. Furthermore, it resulted in a longer lived signaling state, which was formed with a lower quantum yield. Our studies show that the overall effects of the D67N mutation lead to a slightly higher conversion of ATP to cAMP, which points in the direction that by fine tuning the kinetic properties more responsive PACs and optogenetic devices can be generated.

Oral konjac glucomannan for prevention of ionizing radiation-induced injury by regulating gut microbiota and increasing short chain fatty acids.

Ionizing radiation-induced injury commonly happens in radiotherapy, leading to damages of the hematopoietic and gastrointestinal systems. Radioprotective medications are mainly applied in hospitals, although only injections are available and their gut protection is limited. Here, oral konjac glucomannan (KGM), a natural macromolecule and soluble dietary fiber, was used against ionizing radiation-induced injury. The mice were fed with KGM (0.4 g/kg) for 3 days or injected with a clinical medication amifostine before 6.5 Gy γ-ray whole body irradiation (WBI) or 13 Gy whole abdominal irradiation (WAI). In the WBI experiments, KGM improved blood cell recovery and bone marrow cell proliferation in the femur and spleen, though its effect was weaker than or similar to that of amifostine. In the WBI experiments, the gut protection of KGM was similar to or a little better than that of amifostine, involving regenerated crypts numbers, villus length, and gut permeability. Moreover, KGM remarkably enhanced the survival rates of WBI and WAI mice, consistent with amifostine. KGM, as a prebiotic, enhanced gut microbiota abundance, probiotic numbers, and short chain fatty acid production, maintaining gut homeostasis. Moreover, KGM inhibited the apoptosis of irradiated human intestinal epithelial cells. KGM is a promising natural macromolecule against ionizing radiation-induced injury.

A visual method of establishing preperitoneal space for totally visceral sac separation in ventral hernia repair.

OBJECTIVE: To explore a method of visually establishing preperitoneal space. In this paper, the procedure is described in detail and its safety and efficacy evaluated. METHODS: A retrospective style was adopted. The clinical data of 33 patients who accepted the total visceral sac separation (TVS) procedure from December 2019 to November 2021 were collected. Observation indices included location and area of abdominal defect; surgical method and duration of operation to establish preperitoneal space and any postoperative complications; developments during follow-up. Follow-up was performed up to December 2021 using outpatient examination and telephone interview to detect any complications of incision or recurrence of ventral hernia. RESULTS: For operative indices, all patients underwent the TVS procedure successfully except for one who had to be converted to laparoscopic intraperitoneal onlay mesh (IPOM) due to failure to establish preperitoneal space. The time required to establish preperitoneal space was 185.75 ± 44.37 s and the duration of hospital stay was 8.27 ± 1.42 days. No complications, such as abdominal bleeding or digestive tract injury, occurred during hospitalization. No complications of incision were observed during follow up, which lasted 2-24 months with an average of 7 months. CONCLUSIONS: Preliminary results of the novel attempt to establish the preperitoneal space visually confirmed this to be a safe and feasible method. However, the sample size used here was small, with a short follow up. The details and notes need to be further discussed.

Autocatalytic effect boosts the production of medium-chain hydrocarbons by fatty acid photodecarboxylase.

Ongoing climate change is driving the search for renewable and carbon-neutral alternatives to fossil fuels. Photocatalytic conversion of fatty acids to hydrocarbons by fatty acid photodecarboxylase (FAP) represents a promising route to green fuels. However, the alleged low activity of FAP on C2 to C12 fatty acids seemed to preclude the use for synthesis of gasoline-range hydrocarbons. Here, we reveal that Chlorella variabilis FAP (CvFAP) can convert n-octanoic acid in vitro four times faster than n-hexadecanoic acid, its best substrate reported to date. In vivo, this translates into a CvFAP-based production rate over 10-fold higher for n-heptane than for n-pentadecane. Time-resolved spectroscopy and molecular modeling demonstrate that CvFAP's high catalytic activity on n-octanoic acid is, in part, due to an autocatalytic effect of its n-heptane product, which fills the rest of the binding pocket. These results represent an important step toward a bio-based and light-driven production of gasoline-like hydrocarbons.

Consistency evaluation of exercise target heart rate determined by resting heart rate and anaerobic threshold in chronic heart failure patients.

PURPOSE: To evaluate the consistency on the target heart rate for exercise determined by simple target heart rate (sTHR) based on resting heart rate (HRrest) and heart rate at anaerobic threshold (HRAT) in cardiopulmonary exercise test (CPET) for patients with chronic heart failure. METHODS: This is a retrospective cohort study, in which CHF patients who underwent CPET in Tongji Hospital Cardiac Rehabilitation Center Affiliated to Tongji University from March 2007 to December 2018 were enrolled. The clinical data of the patients from the electronic medical record system, HRrest and HRAT measured by CPET were collected. Patients were further divided into subgroups according to gender, age (<60 years group and ≥ 60 years group), with or without beta-blocker therapy and subgroup of heart failure (heart failure with reduced, mid-range and preserved ejection fraction). The sTHR (HRrest plus 10, 15, 20, 25 and 30 bpm) and HRAT were all calculated in each patient. Paired t-test was used for the difference between the two methods, correlation analysis was shown by pearson analysis and intraclass correlation coefficient (ICC) was calculated for consistency test. RESULTS: A total of 547 CHF patients were enrolled, including 447 males (81.7%), aged 63 (56,69) years, with BMI of 25.2 (23.5,26.4) kg/m2 and LVEF of 45.0 (36.0, 52.0) %. The target heart rate determined by HRAT method was (93.59 ± 13.95) bpm, and its counterpart determined by HRrest plus 20 bpm (HRrest+20) was (93.16 ± 7.69) bpm. There was no significant difference between the two methods (P>0.05). However, it was statistically different between HRrest plus 10, 15, 25, 30 bpm and HRAT respectively (P<0.001). And HRrest+20 was positively correlated with HRAT (r = 0.418, P<0.001). Therefore, HRrest+20 below was regarded as sTHR. The ICC of the consistency test between sTHR and HRAT was 0.523,95%CI 0.435-0.596 (P < 0.001) in all patients (n = 547). In patients with beta-blocker therapy (n = 464), the ICC of sTHR and HRAT consistency test was 0.534,95%CI 0.441-0.612, P < 0.001; The ICC of the consistency test between sTHR and HRAT of patients without beta-blocker therapy (n = 83) was 0.407,95%CI 0.083-0.616, P < 0.05. In the sinus rhythm group (n = 466), the ICC of sTHR and HRAT consistency test was 0.527,95%CI 0.433-0.606, P < 0.001; The ICC of the consistency test between sTHR and HRAT of atrial fibrillation patients in group (n = 81) was 0.482,95%CI 0.195-0.667, P < 0.05.The ICC of the consistency test between sTHR and HRAT was 0.501,95%CI 0.338-0.623 (P < 0.001) in patients under 60 years old (n = 195); The ICC of the consistency test between sTHR and HRAT in patients ≥60 years old (n = 352) was 0.533,95%CI 0.424-0.621, P < 0.001. In the male group (n = 447), the ICC of sTHR and HRAT consistency test was 0.577,95%CI 0.491-0.649, P < 0.001; The ICC of the consistency test between sTHR and HRAT of female patients in group (n = 100) was 0.344,95%CI 0.025-0.559, P < 0.05. The ICC of sTHR and HRAT consistency test in HFrEF group (n = 170) was 0.395,95%CI 0.181-0.553, P < 0.01; The ICC values of the consistency test between sTHR and HRAT was 0.543, 95%CI 0.405-0.649 (P < 0.001) in patients with HFmrEF (n = 222); In HFpEF group (n = 155), the ICC of sTHR and HRAT consistency test was 0.620,95%CI 0.478-0.723, P < 0.001. CONCLUSION: The exercise target heart rate calculated by HRrest is consistent with that determined by HRAT in patients with CHF. For primary hospitals without CPET, exercise prescription equivalent to AT intensity for patients with CHF can be determined by HRrest. However, the target heart rate calculated by HRrest can't replace that determined by HRAT in this patient cohort completely.

Predatory bacterial hydrogels for topical treatment of infected wounds.

Wound infection is becoming a considerable healthcare crisis due to the abuse of antibiotics and the substantial production of multidrug-resistant bacteria. Seawater immersion wounds usually become a mortal trouble because of the infection of Vibrio vulnificus. Bdellovibrio bacteriovorus, one kind of natural predatory bacteria, is recognized as a promising biological therapy against intractable bacteria. Here, we prepared a B. bacteriovorus-loaded polyvinyl alcohol/alginate hydrogel for the topical treatment of the seawater immersion wounds infected by V. vulnificus. The B. bacteriovorus-loaded hydrogel (BG) owned highly microporous structures with the mean pore size of 90 µm, improving the rapid release of B. bacteriovorus from BG when contacting the aqueous surroundings. BG showed high biosafety with no L929 cell toxicity or hemolysis. More importantly, BG exhibited excellent in vitro anti-V. vulnificus effect. The highly effective infected wound treatment effect of BG was evaluated on mouse models, revealing significant reduction of local V. vulnificus, accelerated wound contraction, and alleviated inflammation. Besides the high bacterial inhibition of BG, BG remarkably reduced inflammatory response, promoted collagen deposition, neovascularization and re-epithelization, contributing to wound healing. BG is a promising topical biological formulation against infected wounds.

Excited-State Properties of Fully Reduced Flavins in Ferredoxin-NADP+ Oxidoreductase.

The fully reduced flavin cofactor (FADred) in ferredoxin-NADP+ oxidoreductase (FNR) is a functional intermediate that displays different catalytic and steady-state spectral properties for enzymes from Bacillus subtilis (BsFNR), Chlorobaculum tepidum (CtFNR), and Rhodopseudomonas palustris (RpFNR). Using ultrafast spectroscopy, we reveal that at physiological pH, photoexcited FADred in BsFNR and RpFNR exhibits unprecedentedly fast decays (dominantly in 6 and 8 ps, respectively), whereas in CtFNR the decay is much slower (∼400 ps), as in other flavoproteins. Correlating these observations with the protonation states of FADred and the dynamic properties of the protein environment, we conclude that the excited state of neutral FADred can be intrinsically short-lived even in proteins, contrasting with the well-documented behavior of the anionic form that systematically displays markedly increased excited-state lifetime upon binding to proteins. This work provides new insight into the photochemistry of fully reduced flavins, which are emerging as functional initial states in bioengineered photocatalysts.

Circulating tumour cell counts and ultrasomics signature-based nomogram for preoperative prediction of early recurrence of hepatocellular carcinoma after radical treatment.

METHODS: Between December 2017 and December 2018, 153 HCC patients (134 males and 19 females; mean age, 56.0 ± 10.2 years; range, 28-78 years) treated with radical therapy were enrolled in our retrospective study and were divided into a training cohort (n = 107) and a validation cohort (n = 46). All patients underwent preoperative CTC tests and CEUS examinations before treatment. The ultrasomics signature was extracted and built from CEUS images. Univariate and multivariate logistic regression analyses were used to identify the significant variables related to ER, which were then combined to build a predictive nomogram. The performance of the nomogram was evaluated by its discrimination, calibration and clinical utility. The predictive model was further evaluated in the internal validation cohort. RESULTS: HBV DNA, serum AFP level, CTC status, tumour size and ultrasomics score were identified as independent predictors associated with ER (all p < 0.05). Multivariable logistic regression analysis showed that the CTC status (OR = 7.02 [95% CI, 2.07 to 28.38], p = 0.003) and ultrasomics score (OR = 148.65 [95% CI, 25.49 to 1741.72], p < 0.001) were independent risk factors for ER. The nomogram based on ultrasomics score, CTC status, serum AFP level and tumour size exhibited C-indexes of 0.933 (95% CI, 0.878 to 0.988) and 0.910 (95% CI, 0.765 to 1.055) in the training and validation cohorts, respectively, fitting well in calibration curves. Decision curve analysis further confirmed the clinical usefulness of the nomogram. CONCLUSION: The nomogram incorporating CTC, ultrasomics features and independent clinical risk factors achieved satisfactory preoperative prediction of ER in HCC patients after radical treatment. ADVANCES IN KNOWLEDGE: 1. CTC status and ultrasomics score were identified as independent predictors associated with ER of HCC after radical treatment. 2. The nomogram constructed by ultrasomics score generated by 17 ultrasomics features, combined with CTCs and independent clinical risk factors such as AFP and tumour size. 3. The nomogram exhibited satisfactory discriminative power, and could be clinically useful in the preoperative prediction of ER after radical treatment in HCC patients.

Alterations in the gastric microbiota and metabolites in gastric cancer: An update review.

Gastric cancer (GC) is one of the leading causes of cancer mortality worldwide. Numerous studies have shown that the gastric microbiota can contribute to the occurrence and development of GC by generating harmful microbial metabolites, suggesting the possibility of discovering biomarkers. Metabolomics has emerged as an advanced promising analytical method for the analysis of microbiota-derived metabolites, which have greatly accelerated our understanding of host-microbiota metabolic interactions in GC. In this review, we briefly compiled recent research progress on the changes of gastric microbiota and its metabolites associated with GC. And we further explored the application of metabolomics and gastric microbiome association analysis in the diagnosis, prevention and treatment of GC.

Preoperative prognostic value of alfa-fetoprotein density in patients with hepatocellular carcinoma undergoing radiofrequency ablation.

OBJECTIVES: To examine the prognostic value of preoperative alfa-fetoprotein (AFP) density and other clinical factors in patients undergoing percutaneous radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC). METHODS: From January 2010 to December 2018, a total of 543 patients undergoing RFA for HCC meeting the Milan criteria were included at our institution. AFP density was calculated as absolute AFP pre-ablation divided by the total volume of all HCC lesions. The survival rates according to AFP density were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional-hazards regression analyses were used to assess predictors of overall survival (OS) and progression-free survival (PFS). RESULTS: The Kaplan-Meier 1-, 3-, and 5-year OS rates were 98.8%, 88.5%, and 70.4%, respectively, for the low AFP density group, and 98.3%, 74.9%, and 49.4%, respectively, for the high AFP density group. The corresponding PFS rates were 78.9%, 56.7%, and 40.9% (low AFP density group), and 63.6%, 40.8%, and 27.5% (high AFP density group). High AFP density was associated with significantly reduced PFS and OS (both p < 0.001). Multivariate analysis suggested that AFP density was a predictor of OS and PFS. CONCLUSIONS: Serum AFP density may serve as a promising predictor of survival in patients with HCC undergoing RFA. High AFP density could identify patients who might be prone to recurrence or progression and need close surveillance.

Light-triggered on-site rapid formation of antibacterial hydrogel dressings for accelerated healing of infected wounds.

An optimal wound dressing can seal variously shaped wounds and provide a complete barrier to resist bacterial invasion; more importantly, the dressing can be stretched or compressed when the wounds are subjected to external forces and quickly return to its original state after the forces are withdrawn. Here, we designed dressings with light-triggered on-site rapid formation of antibacterial hydrogel for the accelerated healing of infected wounds. The pro-hydrogel, composed of acrylamide (AM) and dopamine-hyaluronic acid-ε-poly-l-lysine (DA-HA-EPL), was filled into the Vibrio vulnificus-infected wound. A 405-nm blue light was exerted on the wound to rapidly photopolymerize AM to its polymer, i.e., polyacrylamide (PAM). A hydrogel network of PAM/DA-HA-EPL immediately formed on site within several seconds to insulate the wound. PAM/DA-HA-EPL possessed adhesion performance to adapt to changes in wound morphologies due to external forces. Moreover, it presented high antibacterial ability due to the presence of EPL, in vitro biocompatibility and the ability to promote cell migration. Vibrio vulnificus-infected wounds were established on full-thickness mouse skin, and the hydrogel dressing exhibited high healing efficiency in terms of skin tissue regeneration, collagen deposition, and angiogenesis. PAM/DA-HA-EPL is a promising hydrogel dressing for the accelerated healing of infected wounds.

NORAD Promotes the Viability, Migration, and Phenotypic Switch of Human Vascular Smooth Muscle Cells during Aortic Dissection via LIN28B-Mediated TGF-ß Promotion and Subsequent Enhanced Glycolysis.

Glucose metabolism reprogramming is an important reason for the functional remodeling, growth, and migration of vascular smooth muscle cells (VSMCs). It is also an important basis for the occurrence and development of aortic dissection (AD), but the specific regulatory factors are not clear. Noncoding RNA activated by DNA damage (NORAD) is dysfunctional in many diseases, but the role of NORAD in AD etiology is unclear. We first established a vascular remodeling cell model of AD, and the expression of NORAD in VSMCs was significantly increased. Functional experiments showed that inhibition of NORAD could downregulate the proliferation and migration of VSMCs. Meanwhile, silencing NORAD could also inhibit the flux of glycolysis, suggesting that NORAD may aggravate AD by promoting glycolysis. In addition, mechanism studies have shown that NORAD can exert VSMCs-regulating function by recruiting LIN28B to bind to TGF-ß mRNA, which subsequently facilitates the expression of TGF-ß1 (transforming growth factor ß1). The recovery experiment also showed that overexpression of TGF-ß could reverse the inhibitory effect of NORAD knockdown on VSMCs in terms of proliferation, migration, and glycolysis. Collectively, these results indicated that the NORAD/LIN28B/TGF-ß axis promoted cell proliferation and migration through regulating aerobic glycolysis in VSMCs. Therefore, NORAD may regulate the occurrence of AD by affecting the reprogramming of glucose metabolism, and NORAD can be recognized as a good target for VSMC phenotypic intervention and AD treatment.

Photochemical and Molecular Dynamics Studies of Halide Binding in Flavoenzyme Glucose Oxidase.

Glucose oxidase (GOX), a characteristic flavoprotein oxidase with widespread industrial applications, binds fluoride (F- ) and chloride (Cl- ). We investigated binding properties of halide inhibitors of GOX through time-resolved spectral characterization of flavin-related photochemical processes and molecular dynamic simulations. Cl- and F- bind differently to the protein active site and have substantial but opposite effects on the population and decay of the flavin excited state. Cl- binds closer to the flavin, whose excited-state decays in <100 fs due to anion-π interactions. Such interactions appear absent in F- binding, which, however, significantly increases the active-site rigidity leading to more homogeneous, picosecond fluorescence decay kinetics. These findings are discussed in relation to the mechanism of halide inhibition of GOX by occupying the accommodation site of catalytic intermediates and increasing the active-site rigidity.

Association of Nationwide Hepatitis B Vaccination and Antiviral Therapy Programs With End-Stage Liver Disease Burden in Taiwan.

Importance: Chronic infections of hepatitis B and C viruses are the main causes of end-stage liver disease (ESLD) worldwide. The successful control of viral hepatitis is critical to reducing the burden of ESLD. Objective: To examine the association of 2 world-first nationwide neonatal hepatitis B vaccinations and national antiviral therapy programs implemented in Taiwan (in 1984 and 2003, respectively) with the burden of ESLD. Design, Setting, and Participants: This cohort study included children and adults aged 5 to 39 years from the National Cancer Registry Database and the National Death Registry Database between 1979 and 2018 in Taiwan. Individuals who died from chronic liver disease (CLD) and cirrhosis and hepatocellular carcinoma (HCC) or were diagnosed with HCC were included for analysis. Analyses were performed in January 2021. Main Outcomes and Measures: The main outcomes were measures of age, period, and cohort associations with CLD mortality and HCC incidence and mortality using an age-period-cohort analysis. Results: Among the 43 604 individuals (mean [SD] age, 33.3 [6.0] years; 37 755 men [86.6%]) with ESLD in the cohort, there were 17 904 CLD deaths, 11 504 HCC deaths, and 14 196 HCC incident events. There was a significant increase in all 3 disease burdens after age 20 years. From 2004 to 2018, CLD mortality decreased by 26% (adjusted rate ratio [aRR], 0.74; 95% CI, 0.70-0.82), HCC mortality decreased by 50% (aRR, 0.50; 95% CI, 0.45-0.58), and HCC incidence decreased by 53% (aRR, 0.47; 95% CI, 0.44-0.52). A sharply declining association by cohort was observed from the 1982 to 1986 birth cohort to the 2007 to 2011 birth cohort, during which CLD mortality decreased by 82% (aRR, 0.18; 95% CI, 0.00-1.13), HCC mortality decreased by 63% (aRR, 0.37; 95% CI, 0.09-0.68), and HCC incidence decreased by 80% (aRR, 0.20; 95% CI, 0.00-0.48). The associations of age, period, and cohort were similar between male and female individuals and between urban and rural areas. The percentage of chronic hepatitis B infections in patients with HCC decreased from 83.3% (95% CI, 79.7%-86.5%) for those born from 1980 to 1984 to 55.6% (95% CI, 21.2%-86.3%) (from 2000 to 2004). Conclusions and Relevance: These findings suggest that the national hepatitis B vaccination program and the antiviral therapy program jointly were associated with substantial reductions in the burden of ESLD in Taiwan.

Inhaled curcumin mesoporous polydopamine nanoparticles against radiation pneumonitis.

Radiation therapy is an effective method to kill cancer cells and shrink tumors using high-energy X-ray or γ-ray. Radiation pneumonitis (RP) is one of the most serious complications of radiation therapy for thoracic cancers, commonly leading to serious respiratory distress and poor prognosis. Here, we prepared curcumin-loaded mesoporous polydopamine nanoparticles (CMPN) for prevention and treatment of RP by pulmonary delivery. Mesoporous polydopamine nanoparticles (MPDA) were successfully synthesized with an emulsion-induced interface polymerization method and curcumin was loaded in MPDA via π‒π stacking and hydrogen bonding interaction. MPDA owned the uniform spherical morphology with numerous mesopores that disappeared after loading curcumin. More than 80% curcumin released from CMPN in 6 h and mesopores recovered. CMPN remarkably protected BEAS-2B cells from γ-ray radiation injury by inhibiting apoptosis. RP rat models were established after a single dose of 15 Gy 60Co γ-ray radiation was performed on the chest area. Effective therapy of RP was achieved by intratracheal administration of CMPN due to free radical scavenging and anti-oxidation ability, and reduced proinflammatory cytokines, high superoxide dismutase, decreased malondialdehyde, and alleviated lung tissue damages were observed. Inhaled CMPN paves a new avenue for the treatment of RP.

Photoswitching Behavior of Flavin-Inhibitor Complex in a Nonphotocatalytic Flavoenzyme.

An unprecedented photoswitching phenomenon of flavin-inhibitor complexes in a flavoenzyme was revealed by femtosecond transient absorption spectroscopy. The vast majority of flavoenzymes, including monomeric sarcosine oxidase (MSOX), perform non-light-driven physiological functions. Yet, the participation of flavin cofactors in photoinduced electron transfer reactions is widespread. MSOX catalyzes the oxidative demethylation of sarcosine; methylthioacetate (MTA) is a substrate analog inhibitor that forms a complex with MSOX exhibiting intense absorption bands over the whole visible range due to flavin-MTA charge transfer (CT) interactions. Here, we demonstrate that upon excitation, these CT interactions vanish during a barrierless high quantum yield reaction in ∼300 fs. The initial complex subsequently geminately re-forms in a few nanoseconds near room temperature in a thermally activated way with an activation energy of 28 kJ/mol. We attribute this hitherto undocumented process to a well-defined photoinduced isomerization of MTA in the active site, as corroborated by experiments with the heavier ligand methylselenoacetate. Photoisomerization phenomena involving CT transitions may be further explored in photocatalytic and photoswitching applications of flavoenzymes.