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Background: Cardiovascular diseases (CVDs) account for 17.9 million deaths annually. Behavioral risk factors increase the risk of dying from CVD. Air pollution is not included in this risk calculation since the appreciation of air pollution as a modifiable risk factor is still limited. The purpose of this study was to analyze CVD mortality attributed to air pollution in all World Health Organization WHO member states and demonstrate the association of CVD mortality with air pollution depending on countries' income level., Methods: The CVD death rate was calculated by dividing the number of deaths by the total population. The proportion of the population with primary reliance on clean fuels and technologies for cooking was calculated as an indicator of household air pollution. The annual mean concentration of fine particulate matter ≤2.5 µg/m 3  and ≤10.0 µg/m 3  to which the population is exposed was used as an indicator of ambient air pollution., Results: There is a gradual increase in CVD mortality attributed to air pollution from high-income countries (HICs) to low-income countries (LICs). Household air pollution is the major cause of CVD mortality in LICs. Ischemic heart disease mortality attributed to ambient air pollution in all countries is higher than stroke mortality attributed to ambient air pollution. In LIC, mortality from stroke is attributed to household air pollution of 39.27 ± 14.47, which is more than twice the stroke mortality attributed to ambient air pollution at 18.60 ± 5.64, t  = 7.17, p  < 0.01., Conclusion: Air pollution control should be an essential component of the CVD preventive strategy, along with lifestyle modifications and effective disease management., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Authors. Chronic Diseases and Translational Medicine published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.)

Background: COVID-19 pandemic represented a shock for healthcare systems. Italy was one of the first country to deal with a huge number of patients to be diagnosed, isolated, and treated with scarce evidence-based guidelines and resources. Several organizational and structural changes were needed to face the pandemic at local level. The article aims at studying the perceived impact of the newly implemented District Operation Centres (DOCs) of Local Health Authority (LHA) Roma 1 in managing active surveillance and home care of COVID-19 patients and their close contacts in cooperation with general practitioners (GPs)., Methods: A questionnaire, developed according to Delphi methodology, was validated by 7 experts and administered to a randomized sample of GPs and family paediatricians (FPs). All medical doctors selected received a phone interview between December 2020 and January 2021. The questionnaire investigated general characteristics of the sample, relations with DOC and its usefulness, and potential developments. A descriptive analysis was performed and inferential statistical tests were used to assess differences., Results: In April 2020 the LHA Roma 1 implemented one DOCs in each local health district. 215 medical doctors were interviewed, reaching the sample target for health districts (80% CL and 10% MOE) and the whole LHA (90% CL and 5% MOE). Several aspects in the management of COVID-19 cases and close contacts of COVID-19 cases, and of the support of DOCs to GPs/FPs were investigated. More than 55% of the GPs and FPs interviewed found the DOCs useful and more than 78% would recommend a service DOC-like to other LHAs. The medical professionals interviewed would use DOCs in the future as support in treating vulnerable patients, utilizing digital health tools, enlisting specialist doctors, establishing networks, and facilitating professional counselling by nurses., Conclusions: This study is an attempt to evaluate an organizational change happened during COVID-19 pandemic. DOCs were created to support GPs and FPs as a link between primary healthcare and public health. Although several difficulties were disclosed, DOCs' experience can help to overcome the fragmentation of the systems and the duality between primary care and public health and make the system more resilient., (© 2023. The Author(s).)

Background: Non-communicable diseases (NCDs) are major cause of death all over the world killing 41 million of the 57 million deaths (72%) in 2016. According to World Health Organization (WHO) Director General the biggest decrease in NCD mortality between 2000 and 2019 globally were for chronic respiratory diseases (CRDs) a 37% decline. The WHO Western Pacific Region (WPRO) made the biggest gains against CRD a 55.9% drop. We analysed CRD mortality in the WPRO comparing with other WHO regions., Methods: Assessment of the risk factors was made in all WHO countries mainly in 2016. Lifestyle modifications concerning tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol in 2020. We used WHO assessment of ambient and household air pollution attributable to chronic obstructive pulmonary disease (COPD) mortality., Results: WPRO comprises 27 countries, 10 high-income countries (HIC) and 17 middle-income countries (MIC). A total of 52 countries in other WHO regions belong to HIC and 86 countries to MIC. No difference was found in the tobacco demand-reduction measures. Clear difference was demonstrated in the prevalence of the raised blood pressure (RBP) which was lower in the WPRO. In the WPRO HIC every fifth has RBP while in other regions it was every forth. Similar difference was observed for MIC. COPD mortality linked to air pollution was twice higher in the WPRO. It was highest in MIC. CRD management probably plays a crucial role in the decline of the observed mortality in the region since numerous WHO global, regional and national prevention and management CRD approaches and activities have been successfully initiated and implemented there. WHO Global Alliance against Chronic Respiratory Diseases (GARD) was successfully initiated in Beijing in 2006. Two subsequent global GARD meetings held in Seoul [2007] and Beijing [2019] had a tremendous impact on the CRD awareness, prevention and control strategies in the region. These events have stimulated development of the national CRD programmes. Beijing's declaration "Call for action for lung health" stressed the better management of CRD at primary healthcare level., Conclusions: Better RBP control, improved prevention, diagnosis and treatment of CRD could contribute to the observed decline of premature CRD mortality in the region., Competing Interests: Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1466/coif). The series “GARD Section” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Sleep is vital for most animals, yet its mechanism and function remain unclear. We found that permeability of the BBB (blood-brain barrier)-the organ required for the maintenance of homeostatic levels of nutrients, ions, and other molecules in the brain-is modulated by sleep deprivation (SD) and can cell-autonomously effect sleep changes. We observed increased BBB permeability in known sleep mutants as well as in acutely sleep-deprived animals. In addition to molecular tracers, SD-induced BBB changes also increased the penetration of drugs used in the treatment of brain pathologies. After chronic/genetic or acute SD, rebound sleep or administration of the sleeping aid gaboxadol normalized BBB permeability, showing that SD effects on the BBB are reversible. Along with BBB permeability, RNA levels of the BBB master regulator moody are modulated by sleep. Conversely, altering BBB permeability alone through glia-specific modulation of moody, gαo, loco, lachesin , or neuroglian -each a well-studied regulator of BBB function-was sufficient to induce robust sleep phenotypes. These studies demonstrate a tight link between BBB permeability and sleep and indicate a unique role for the BBB in the regulation of sleep.

Molecular photoswitches are the foundation of light-activated drugs. A key photoswitch is azobenzene, which exhibits trans - cis isomerism in response to light. The thermal half-life of the cis isomer is of crucial importance, since it controls the duration of the light-induced biological effect. Here we introduce a computational tool for predicting the thermal half-lives of azobenzene derivatives. Our automated approach uses a fast and accurate machine learning potential trained on quantum chemistry data. Building on well-established earlier evidence, we argue that thermal isomerization proceeds through rotation mediated by intersystem crossing, and incorporate this mechanism into our automated workflow. We use our approach to predict the thermal half-lives of 19,000 azobenzene derivatives. We explore trends and trade-offs between barriers and absorption wavelengths, and open-source our data and software to accelerate research in photopharmacology., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: Noncommunicable diseases (NCDs) place a heavy burden on populations globally and in particular, on lower-income countries (LIC). WHO identified a package of 16 "best buy" lifestyle and management interventions that are cost-effective and applicable in all settings. The purpose of this study was to evaluate and compare NCD risk factors in all WHO countries and make preliminary assessment of "best buy" interventions., Methods: Risk factors estimation was made in 188 countries. NCD attributable "best buys" concern tobacco use, unhealthy diet, physical inactivity, and harmful use of alcohol. Management issues are based on the availability of the national NCD guidelines and provision of drug therapy., Results: Every fourth adult in high-income countries (HIC) has raised blood pressure (RBP). Prevalence of RBP in lower-middle-income countries (LMIC) and LIC is 22%-23% (HIC/LMIC: t  =  3.12 , p  <  0.01 ). Prevalence of diabetes in LIC is less than half of that in HIC and upper-middle-income countries (UMIC) UMIC/LIC: t = 8.37 , p < 0.001 . Obesity prevalence is gradually decreasing from HIC to LIC (HIC/LIC: t = 11.48 , p < 0.001 ). Highest level of physical inactivity is seen in HIC, which then gradually declines to LIC (17%). Tobacco prevalence in LIC is almost less than half of that in HIC and UMIC (HIC/LIC: t = 7.2 , p < 0.0001 ). There is a gradual decline in the implementation of "best buys" from HIC to LIC., Conclusion: Wealthier countries have better implementation of the WHO NCD prevention strategy., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Chronic Diseases and Translational Medicine published by John Wiley & Sons, Ltd on behalf of Chinese Medical Association.)

Background: Cardiovascular disease (CVD) is the major noncommunicable disease (NCD) accounting for 17.9 million deaths. If current trends continue, the annual number of deaths from CVD will rise to 22.2 million by 2030. The United Nations General Assembly adopted a sustainable development goal (SDG) by 2030 to reduce NCD mortality by one-third. The purpose of this study was to analyze the CVD mortality trends in different countries implementing World Health Organization (WHO) NCD Action Plan and emphasize effective ways to achieve SDG., Methods: WHO statistics, based on the Member-States unified mortality and causes-of-death reports were used for analyzing trends and different interventions., Results: Reduction of CVD mortality from 2000 to 2016 in 49 countries was achieved for stroke at 43% and ischemic heart disease at 30%. Smoking prevalence and raised blood pressure (RBP) decreased in 84% and 55% of the countries. Eighty-nine percent of high-income countries (HIC) demonstrated a decline in tobacco smoking against 67% in middle-income countries (MIC). Sixty-nine percent of HIC demonstrated a decline in RBP against 15% in MIC. CVD management, tobacco, and unhealthy diet reduction measures are significantly better in HIC. The air pollution level was higher in MIC., Conclusion: Building partnerships between countries could enhance their efforts for CVD prevention and successful achievement of SDG., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Chronic Diseases and Translational Medicine published by John Wiley & Sons Ltd on behalf of Chinese Medical Association.)

Light-induced chemical processes are ubiquitous in nature and have widespread technological applications. For example, photoisomerization can allow a drug with a photo-switchable scaffold such as azobenzene to be activated with light. In principle, photoswitches with desired photophysical properties like high isomerization quantum yields can be identified through virtual screening with reactive simulations. In practice, these simulations are rarely used for screening, since they require hundreds of trajectories and expensive quantum chemical methods to account for non-adiabatic excited state effects. Here we introduce a diabatic artificial neural network (DANN), based on diabatic states, to accelerate such simulations for azobenzene derivatives. The network is six orders of magnitude faster than the quantum chemistry method used for training. DANN is transferable to azobenzene molecules outside the training set, predicting quantum yields for unseen species that are correlated with experiment. We use the model to virtually screen 3100 hypothetical molecules, and identify novel species with high predicted quantum yields. The model predictions are confirmed using high-accuracy non-adiabatic dynamics. Our results pave the way for fast and accurate virtual screening of photoactive compounds., (© 2022. The Author(s).)

Machine learning (ML) outperforms traditional approaches in many molecular design tasks. ML models usually predict molecular properties from a 2D chemical graph or a single 3D structure, but neither of these representations accounts for the ensemble of 3D conformers that are accessible to a molecule. Property prediction could be improved by using conformer ensembles as input, but there is no large-scale dataset that contains graphs annotated with accurate conformers and experimental data. Here we use advanced sampling and semi-empirical density functional theory (DFT) to generate 37 million molecular conformations for over 450,000 molecules. The Geometric Ensemble Of Molecules (GEOM) dataset contains conformers for 133,000 species from QM9, and 317,000 species with experimental data related to biophysics, physiology, and physical chemistry. Ensembles of 1,511 species with BACE-1 inhibition data are also labeled with high-quality DFT free energies in an implicit water solvent, and 534 ensembles are further optimized with DFT. GEOM will assist in the development of models that predict properties from conformer ensembles, and generative models that sample 3D conformations., (© 2022. The Author(s).)

The COVID-19 pandemic called for a reorganisation of the methods for providing health services. The aim of this paper is to describe the organisational model implemented by one of Rome's Local Health Units (LHU), ASL Roma 1, for the "at-home COVID-19 vaccination campaign" dedicated to a target population and to outline data related to vaccination coverage stratified by health districts. A cross-sectional study was designed to describe the strategies implemented by LHU to deliver at-home vaccination programmes. People eligible for the at-home vaccination programme included patients living in the area of the LHU, being assisted by the district home care centre or not transportable or individuals with social situations that make traveling difficult. Priority for vaccination was given to (I) age > 80 years, (II) ventilated patients with no age limit, (III) very seriously disabled people with no age limit. Patients' data were acquired from regional and LHU databases. From 5 February until the 16 May, 6127 people got at least one dose of Pfizer-Biontech Comirnaty ® vaccine, while 5278 (86.14%) completed the necessary two doses. The highest number of vaccines was administered during the first week of April, reaching 1296 doses overall. The number of vaccines administered were similar across the districts. The average number of people vaccinated at home was 6 per 1000 inhabitants in the LHU. This model proved to be extremely complex but effective, reaching satisfying results in terms of vaccination coverage.

Carbohydrate-binding proteins (lectins) play vital roles in cell recognition and signaling, including pathogen binding and innate immunity. Thus, targeting lectins, especially those on the surface of immune cells, could advance immunology and drug discovery. Lectins are typically oligomeric; therefore, many of the most potent ligands are multivalent. An effective strategy for lectin targeting is to display multiple copies of a single glycan epitope on a polymer backbone; however, a drawback to such multivalent ligands is they cannot distinguish between lectins that share monosaccharide binding selectivity (e.g., mannose-binding lectins) as they often lack molecular precision. Here, we describe the development of an iterative exponential growth (IEG) synthetic strategy that enables facile access to synthetic glycomacromolecules with precisely defined and tunable sizes up to 22.5 kDa, compositions, topologies, and absolute configurations. Twelve discrete mannosylated "glyco-IEGmers" are synthesized and screened for binding to a panel of mannoside-binding immune lectins (DC-SIGN, DC-SIGNR, MBL, SP-D, langerin, dectin-2, mincle, and DEC-205). In many cases, the glyco-IEGmers had distinct length, stereochemistry, and topology-dependent lectin-binding preferences. To understand these differences, we used molecular dynamics and density functional theory simulations of octameric glyco-IEGmers, which revealed dramatic effects of glyco-IEGmer stereochemistry and topology on solution structure and reveal an interplay between conformational diversity and chiral recognition in selective lectin binding. Ligand function also could be controlled by chemical substitution: by tuning the side chains of glyco-IEGmers that bind DC-SIGN, we could alter their cellular trafficking through alteration of their aggregation state. These results highlight the power of precision synthetic oligomer/polymer synthesis for selective biological targeting, motivating the development of next-generation glycomacromolecules tailored for specific immunological or other therapeutic applications., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Background: According to the World Health Organization (WHO), a global reduction of 17% has been achieved in the major noncommunicable disease-associated mortality rate since 2000. This decline was due to the decreasing mortality associated with cardiovascular and chronic respiratory diseases. The WHO has not made any comments on diabetes-related mortality thus far. The objective of this study was to demonstrate trends in diabetes-related mortality associated with country-wide interventions., Methods: The WHO statistics were used to assess trends in diabetes-related mortality from 2000 to 2016. Different types of community-based interventions in 49 countries were compared and assessed., Results: The baseline mortality decreased by 7%. Mortality in middle-income countries was higher than that in high-income countries. The prevalence of obesity showed a gradual increase in all countries. After implementation of the WHO "best buy" in 2010, mortality increased in 17 countries and decreased in 32 countries. Regarding the smoking prevalence trend, 87% countries with decreasing diabetes-related mortality had a gradual decline in tobacco usage since 2000. The decline was observed only in 43% countries with increasing diabetes-related mortality. The prevalence of hypertension increased in 19% countries with declining diabetes-related mortality and in 35% countries with increasing diabetes-related mortality. Physical activity measures tended to be better implemented in countries with declining diabetes-related mortality than in countries with increasing diabetes-related mortality., Conclusion: Smoking cessation and better blood pressure control are associated with declining diabetes-related mortality. Longer implementation periods are needed for other lifestyle interventions., Competing Interests: None., (© 2021 Chinese Medical Association. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd.)

Competing Interests: The authors have declared that no competing interests exist.

Background: According to the Independent High-level Commission on Non-communicable Diseases (NCD) of the World Health Organization (WHO), global reduction in lung cancer mortality has been achieved since the year 2000, although this effect is not sufficient to reach the 30% reduction of mortality from NCDs by the year 2030, as stipulated by the United Nations Sustainable Development Goal 3.4. The objective of this study was to analyze whether the lifestyle changes implemented by the WHO at country level could have an impact on mortality from this form of cancer., Methods: WHO statistics, based on the unified mortality and causes-of-death reports of Member-State countries, were used to evaluate global lung cancer mortality trends and make comparisons and assessments of different types of community-based, country-wide interventions., Results: The lung cancer mortality decline was associated with the anti-tobacco campaign initiated by the WHO in the last 15 to 20 years. Comprehensive tobacco control remained the major and most successful lifestyle modification measure. In countries with declining lung cancer mortality, 91% of countries had decreasing tobacco prevalence in males and 82% in females. Country- wide measures to increase physical activity had a strong tendency to be better implemented in countries with declining lung cancer mortality (t = 1.79, P > 0.05). Other WHO "best-buy" lifestyle modification campaigns (diet and alcohol) had been carried out for shorter periods, and their associations with lung cancer were less strong than tobacco. There was no significant difference between countries with declining and increasing lung cancer mortality in the measures for reduction of harmful alcohol use (t = 0.92, P > 0.05) and unhealthy diet reduction measures (t = 0.84, P > 0.05)., Conclusion: Following WHO "best-buys" should facilitate to move countries towards the NCD including lung cancer mortality reduction targets. Governments and communities must embrace these targets with coordinated effective action for better health.

Circadian rhythmicity of gene expression is a conserved feature of cell physiology. This involves fine-tuning between transcriptional and post-transcriptional mechanisms and strongly depends on the metabolic state of the cell. Together these processes guarantee an adaptive plasticity of tissue-specific genetic programs. However, it is unclear how the epigenome and RNA Pol II rhythmicity are integrated. Here we show that the PcG protein EZH1 has a gateway bridging function in postmitotic skeletal muscle cells. On the one hand, the circadian clock master regulator BMAL1 directly controls oscillatory behavior and periodic assembly of core components of the PRC2-EZH1 complex. On the other hand, EZH1 is essential for circadian gene expression at alternate Zeitgeber times, through stabilization of RNA Polymerase II preinitiation complexes, thereby controlling nascent transcription. Collectively, our data show that PRC2-EZH1 regulates circadian transcription both negatively and positively by modulating chromatin states and basal transcription complex stability., (© 2024. The Author(s).)

Purpose: Limited means exist to assess gastrointestinal activity in pediatric patients postoperatively. Recently, myoelectric gastrointestinal activity recorded by cutaneous patches has been shown in adult patients to be predictive of clinical return of gastrointestinal function postoperatively. The aim of this case series is to demonstrate the feasibility of this system in pediatric patients and to correlate myoelectric signals with return of bowel function clinically., Methods: Pediatric patients undergoing abdominal surgery were recruited to have wireless patches placed on the abdomen within two hours postoperatively. Myoelectric data were transmitted wirelessly to a mobile device with a user-interface and forwarded to a cloud server where processing algorithms identified episodes of motor activity, quantified their parameters and nominally assigned them to specific gastrointestinal organs based on their frequencies., Results: Three patients (ages 5 months, 4 year, 16 year) were recruited for this study. Multiple patches were placed on the older subjects, while the youngest had a single patch due to space limitations. Rhythmic signals of the stomach, small intestine, and colon could be identified in all three subjects. Patients showed gradual increase in myoelectric intestinal and colonic activity leading up to the first recorded bowel movement., Conclusion: Measuring myoelectric intestinal activity continuously using a wireless patch system is feasible in a wide age range of pediatric patients. The increase in activity over time correlated well with the patients' return of bowel function. More studies are planned to determine if this technology can predict return of bowel function or differentiate between physiologic ileus and pathologic conditions., Competing Interests: Conflict of Interest: Anand Navalgund, Lindsay Axelrod and Steve Axelrod are employees of G-Tech Medical. Patches for this study were supplied by G-Tech Medical. The other authors have no disclosures related to this work., (Copyright © 2019 by The Korean Society of Pediatric Gastroenterology, Hepatology and Nutrition.)

Postoperative delayed gastric emptying (DGE) is a frustrating complication of pancreaticoduodenectomy (PD). We studied whether monitoring of postoperative gastric motor activity using a novel wireless patch system can identify patients at risk for DGE. Patients ( n = 81) were prospectively studied since 2016; 75 patients total were analyzed for this study. After PD, battery-operated wireless patches (G-Tech Medical) that acquire gastrointestinal myoelectrical signals are placed on the abdomen and transmit data by Bluetooth. Patients were divided into early and late groups by diet tolerance of 7 days [enhanced recovery after surgery (ERAS) goal]. Subgroup analysis was done of patients included after ERAS initiation. The early and late groups had 50 and 25 patients, respectively, with a length of stay (LOS) of 7 and 11 days ( P < 0.05). Nasogastric insertion was required in 44% of the late group. Tolerance of food was noted by 6 versus 9 days in the early versus late group ( P < 0.05) with higher cumulative gastric myoelectrical activity. Diminished gastric myoelectrical activity accurately identified delayed tolerance to regular diet in a logistical regression analysis [area under the curve (AUC): 0.81; 95% confidence interval (CI), 0.74-0.92]. The gastric myoelectrical activity also identified a delayed LOS status with an AUC of 0.75 (95% CI, 0.67-0.88). This stomach signal continued to be predictive in 90% of the ERAS cohort, despite earlier oral intake. Measurement of gastric activity after PD can distinguish patients with shorter or longer times to diet. This noninvasive technology provides data to identify patients at risk for DGE and may guide the timing of oral intake by gastric "readiness." NEW & NOTEWORTHY Limited clinical indicators exist after pancreaticoduodenectomy to allow prediction of delayed gastric emptying (DGE). This study introduces a novel, noninvasive, wireless patch system capable of accurately monitoring gastric myoelectric activity after surgery. This system can differentiate patients with longer or shorter times to a regular diet as well as provide objective data to identify patients at risk for DGE. This technology has the potential to individualize feeding regimens based on gastric activity patterns to improve outcomes.

Objectives. We assessed the impact of a rewards-based incentive program on fruit and vegetable purchases by low-income families. Methods. We conducted a 4-phase prospective cohort study with randomized intervention and wait-listed control groups in Philadelphia, Pennsylvania, in December 2010 through October 2011. The intervention provided a rebate of 50% of the dollar amount spent on fresh or frozen fruit and vegetables, reduced to 25% during a tapering phase, then eliminated. Primary outcome measures were number of servings of fruit and of vegetables purchased per week. Results. Households assigned to the intervention purchased an average of 8 (95% confidence interval [CI] = 1.5, 16.9) more servings of vegetables and 2.5 (95% CI = 0.3, 9.5) more servings of fruit per week than did control households. In longitudinal price-adjusted analyses, when the incentive was reduced and then discontinued, the amounts purchased were similar to baseline. Conclusions. Investigation of the financial costs and potential benefits of incentive programs to supermarkets, government agencies, and other stakeholders is needed to identify sustainable interventions.

Background: Melatonin (MLT) and its receptor deficiency have been shown to be associated with type 2 diabetes mellitus (T2DM). Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive alternative intervention for patients suffering from hyperglycemia. Here, we aimed to investigate the role of taVNS on blood glucose modulation via intestinal melatonin receptors (MRs) and MLT secretion in hyperglycemia. Methods: Adult male Zucker diabetes fatty (ZDF) rats and Zucker lean (ZL) littermates were used. Forty ZDF rats were randomized into ZDF, taVNS, Px + taVNS and Lu + Px + taVNS groups (Px: pinealectomy, Lu: Luzindole). ZL rats served as a control group for comparison with ZDF rats without involvement in the taVNS intervention. Thirty min-taVNS interventions (2/15 Hz, 2 mA, 30 min/days) were administered once daily under anesthesia for 3 consecutive weeks in taVNS, Px + taVNS and Lu + Px + taVNS groups. Body weight and fasting blood glucose (FBG) were measured weekly in all rats, and real-time blood glucose was tested in the ZL and ZDF groups before, during and after the taVNS intervention. Plasma MLT concentration and the expression of MRs in the duodenum, jejunum and ileum were measured by the end of experiments. Results: Compared with the ZL group, the level of FBG and body weight increased (all p < 0.01), plasma MLT secretion and the expression of MRs in duodenum, jejunum and ileum of ZDF rats decreased obviously (all p < 0.05), respectively. TaVNS can significantly reverse the hyperglycemia by regulating the non-pineal-derived MLT and MRs system in Px + taVNS group. Compared with the ZDF group, the expression of different intestinal MRs in the taVNS group was increased and more compactly arranged (both p < 0.05), the level of plasma MLT secretion was up-regulated (p < 0.01), and FBG and body weight were decreased (both p < 0.01). Meanwhile, after taVNS intervention in rats in the Px + taVNS group, we observed an increase in MLT secretion and the number of intestinal MRs compared with the taVNS group (all p > 0.05). In contrast, ZDF rats in which the pineal gland was excised by taVNS intervention and injected with the MRs antagonist Luzindole did not show these changes. Conclusion: The glucose reduction effect of taVNS may be related to regulating MLT levels and expressing intestinal MRs. [ABSTRACT FROM AUTHOR]

The circadian clock is a cell-autonomous process that regulates daily internal rhythms by interacting with environmental signals. Reports across species show that infection can alter the expression of circadian genes; however, in teleosts, these effects are influenced by light exposure. Currently, no reports analyze the direct effects of bacterial exposure on the zebrafish clock. Using zebrafish Z3 cells, we demonstrate that exposure to heat-killed Streptococcus pneumoniae (HK-Spn) augments the expression of core repressive factors in a light- and time-dependent manner. In constant darkness, HK-Spn highly upregulated cry1a, per3, and per1b expression. In the presence of light, HK-Spn exposure rapidly and strongly upregulated per2 and cry1a, and this was proportionally increased with light intensity. The combinatorial effect of light and HK-Spn on per2 and cry1a was not duplicated with H2O2, a known byproduct of light exposure. However, the ROS inhibitor N-acetyl cysteine was sufficient to block HK-Spn augmentation of per2, cry1a, and per3. These findings demonstrate that exposure to an inactive bacteria influences the expression of zebrafish clock genes under different light conditions. [ABSTRACT FROM AUTHOR]

The circadian clock is an autonomous timekeeping system evolved by organisms to adapt to external changes, regulating a variety of important physiological and behavioral processes. Recent studies have shown that the sirtuin family of histone deacetylases is involved in regulating the expression of clock genes and plays an important role in maintaining the normal rhythm of clock gene expression and behavior. Moreover, sirtuins are regulated directly or indirectly by the circadian clock system. The mutual regulation between the circadian clock and sirtuins is likely involved in a variety of signal transduction and metabolism processes. In this review, we discuss the molecular mechanisms and research progress on the intertwined relationship between the circadian clock and sirtuins, mainly in mammals, highlighting sirtuins as molecular links between metabolic control and circadian rhythms and offering our perspectives on future developments in the field. [ABSTRACT FROM AUTHOR]

Many studies of azobenzene photoswitches are carried out in polar aprotic solvents as a first principles characterization of thermal isomerization. Among the most convenient polar aprotic solvents are chlorinated hydrocarbons, such as DCM. However, studies of azobenzene thermal isomerization in such solvents have led to spurious, inconclusive, and irreproducible results, even when scrupulously cleaned and dried, a phenomenon not well understood. We present the results of a comprehensive investigation into the root cause of this problem. We explain how irradiation of an azopyridine photoswitch with UV in DCM acts not just as a trigger for photoisomerization, but protonation of the pyridine moiety through photodecomposition of the solvent. Protonation markedly accelerates the thermal isomerization rate, and DFT calculations demonstrate that the singlet-triplet rotation mechanism assumed for many azo photoswitches is surprisingly abolished. This study implies exploitative advantages of photolytically-generated protons and finally explains the warning against using chlorinated solvent with UV irradiation in isomerization experiments. Azobenzenes undergo reversible light-induced photoisomerization, resulting in marked spectroscopic, electronic, and mechanical changes, but their sensitivity towards solvents is not fully understood. Here, the authors report how irradiation of an azopyridine photoswitch with UV light in dichloromethane triggers protonation of the pyridine moiety through photodecomposition of the solvent, consequently accelerating thermal back isomerization and abolishing singlet-triplet rotation mechanisms. [ABSTRACT FROM AUTHOR]

Circadian dysfunction is prevalent in neurodevelopmental disorders, particularly in autism spectrum disorder (ASD). A plethora of empirical studies demonstrate a strong correlation between ASD and circadian disruption, suggesting that modulation of circadian rhythms and the clocks could yield satisfactory advancements. Research indicates that circadian dysfunction associated with abnormal neurodevelopmental phenotypes in ASD individuals, potentially contribute to synapse plasticity disruption. Therefore, targeting circadian rhythms may emerge as a key therapeutic approach. In this study, we did a brief review of the mammalian circadian clock, and the correlation between the circadian mechanism and the pathology of ASD at multiple levels. In addition, we highlight that circadian is the target or modulator to participate in the therapeutic approaches in the management of ASD, such as phototherapy, melatonin, modulating circadian components, natural compounds, and chronotherapies. A deep understanding of the circadian clock's regulatory role in the neurodevelopmental phenotypes in ASD may inspire novel strategies for improving ASD treatment. [ABSTRACT FROM AUTHOR]

The role of circadian rhythm genes (CRGs) in gastric cancer (GC) is poorly understood. This study aimed to develop a CRG signature to improve understanding of prognosis and immunotherapy responses in GC patients. We integrated the The Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD) dataset with CRGs to develop a prognostic signature for GC. The signature's predictive ability was validated using Kaplan-Meier and ROC curves. The CIBERSORT algorithm evaluated immune cell proportions, and tumor immune dysfunction and exclusion score, as well as immune phenotype score, determined the response to immunotherapy for STAD patients. Finally, we assessed signature genes expression using real-time quantitative polymerase chain reaction. We developed a 4-CRG signature for STAD, demonstrating accurate prognostic ability. The low-risk group showed increased B cell memory and CD8 + T cells, and decreased M2 Macrophages compared to the high-risk group. Patients in the low-risk group had a higher likelihood of benefiting from immunotherapy. Additionally, gastric cancer tissues exhibited elevated expression of OPN3 and decreased expression of TP53 compared to adjacent tissue. This study successfully established a prognostic signature for CRGs, accurately predicting prognosis and immunotherapeutic response among STAD patients, providing insights for the development of personalized therapeutic strategies for these patients. [ABSTRACT FROM AUTHOR]

In this work we introduce GrapheNet, a deep learning framework based on an Inception-Resnet architecture using image-like encoding of structural features for the prediction of the properties of nanographenes. The model is validated on datasets of computed structure/property data on graphene oxide and defected graphene nanoflakes. By exploiting the planarity of quasi-bidimensional systems and through encoding structures into images, and leveraging the flexibility and power of deep learning in image processing, Graphenet achieves significant accuracy in predicting the physicochemical properties of nanographenes. This approach is able to efficiently encode structures composed of hundreds of atoms, scaling efficiently with the size of the model and enabling the prediction of the properties of large systems, which contrasts with the limitations of current atomistic-level representations for deep learning applications. The approach proposed based on image encoding exhibit a significant numerical accuracy and outperforms the computational efficiency of current representations of materials at the atomistic level, with significant advantages especially in the representation of nanostructures and large planar systems. [ABSTRACT FROM AUTHOR]

Circadian rhythms, the internal timekeeping systems governing physiological processes, significantly influence skin health, particularly in response to ultraviolet radiation (UVR). Disruptions in circadian rhythms can exacerbate UVR-induced skin damage and increase the risk of skin aging and cancer. This review explores how circadian rhythms affect various aspects of skin physiology and pathology, with a special focus on DNA repair. Circadian regulation ensures optimal DNA repair following UVR-induced damage, reducing mutation accumulation, and enhancing genomic stability. The circadian control over cell proliferation and apoptosis further contributes to skin regeneration and response to UVR. Oxidative stress management is another critical area where circadian rhythms exert influence. Key circadian genes like brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) modulate the activity of antioxidant enzymes and signaling pathways to protect cells from oxidative stress. Circadian rhythms also affect inflammatory and immune responses by modulating the inflammatory response and the activity of Langerhans cells and other immune cells in the skin. In summary, circadian rhythms form a complex defense network that manages UVR-induced damage through the precise regulation of DNA damage repair, cell proliferation, apoptosis, inflammatory response, oxidative stress, and hormonal signaling. Understanding these mechanisms provides insights into developing targeted skin protection and improving skin cancer prevention. [ABSTRACT FROM AUTHOR]

Background: Non-communicable diseases (NCDs) represent a global health challenge, accounting for 74% of deaths worldwide. One of the recommended interventions to reduce the risk of NCDs is the implementation of warning labels (WLs) on food products to alert consumers about high levels of undesirable nutrients, such as sugar or saturated fats. We aimed to conduct a bibliometric analysis of scientific literature related to WL policies in food and beverages to evaluate global trends and collaborations. Methods: A bibliometric analysis was performed using the Web of Science Core Collection (WoSCC). Articles published between 1998 and 2023 were retrieved using the search terms "warning labels" AND "food" OR "beverage". Bibliometric indicators, including publication counts, citations, collaborations, and thematic trends, were analyzed using the Bibliometrix package in R and VOSviewer. Results: We included 255 articles on WLs. Scientific production increased markedly from 2018 onwards, with over 30 articles published annually from 2018 to 2023. The most cited article, by Taillie et al., focused on the impact of Chile's WL policies. The United States had the largest scientific production, followed by Brazil and Chile. Nutrients was the journal with the most publications on this topic. Conclusions: The growth in WL-related research, particularly in Latin America, reflects the increasing implementation of these policies. These results underscore key collaborations and evolving research themes, from food labeling to broader public health impacts, emphasizing the need for continued evaluation of WL effectiveness. [ABSTRACT FROM AUTHOR]

The regulation of the mammalian circadian clock is largely dependent on heredity. In model animals for circadian rhythm studies, C57BL/6 and BALB/c mice exhibit considerable differences in their adaptation to circadian disruption, yet deeper comparisons remain unexplored. Here, we have established embryonic fibroblast cells derived from C57BL/6 mice (MEF) and BALB/c (BALB/3T3) mice, which have been transfected with the Bmal1 promoter-driven luciferase (Bmal1-Luc) reporter gene. Next, dexamethasone was applied for various cyclic stimulations, which revealed that Bmal1 bioluminescence of MEF cells was entrained to 24 to 26 h cycles, whereas BALB/3T3 cells have a wider range (22 to 28 h) with lower amplitudes. Behaviorally, BALB/c mice swiftly adapted to a 6-h advance light/dark cycle, unlike C57BL/6 mice. Furthermore, we found the expression of the circadian rhythm gene Npas2 in BALB/c mice is significantly lower than that in C57BL/6 mice. This observation is consistent with the differentially expressed genes (DEGs) in the intestine and lung tissues of C57BL/6 and BALB/c mice, based on the RNA-seq datasets downloaded from the Gene Expression Omnibus (GEO). In summary, our study uncovers that BALB/c mice possess greater resilience in circadian rhythm than C57BL/6 mice, both cellular and behaviorally, identifying potential genes underlying this difference. [ABSTRACT FROM AUTHOR]

Understanding time-series interplay of genes is essential for diagnosis and treatment of disease. Spatio-temporally enriched NGS data contain important underlying regulatory mechanisms of biological processes. Generative adversarial networks (GANs) have been used to augment biological data to describe hidden intermediate time-series gene expression profiles during specific biological processes. Developing a pipeline that uses augmented time-series gene expression profiles is needed to provide an unbiased systemic-level map of biological processes and test for the statistical significance of the generated dataset, leading to the discovery of hidden intermediate regulators. Two analytical methods, GAN-WGCNA (weighted gene co-expression network analysis) and rDEG (rescued differentially expressed gene), interpreted spatiotemporal information and screened intermediate genes during cocaine addiction. GAN-WGCNA enables correlation calculations between phenotype and gene expression profiles and visualizes time-series gene module interplay. We analyzed a transcriptome dataset of two weeks of cocaine self-administration in C57BL/6J mice. Utilizing GAN-WGCNA, two genes (Alcam and Celf4) were selected as missed intermediate significant genes that showed high correlation with addiction behavior. Their correlation with addictive behavior was observed to be notably significant in aspect of statistics, and their expression and co-regulation were comprehensively mapped in terms of time, brain region, and biological process. [ABSTRACT FROM AUTHOR]

Air pollution has become one of the biggest problems throughout the world. Smog has a severe effect on the pulmonary and circulatory systems, which causes a significant number of deaths globally. Therefore, the remediation of air pollutants to maintain ecosystem processes and functions and to improve human health is a crucial problem confronting mankind today. This review aims to discuss the health effects of smog on humans. This review will also focus on the bioremediation of air pollution (smog) using bacteria, fungi, phytoremediation, nanotechnology, and phylloremediation (using plants and microbes). Phylloremediation is the most effective technology for removing air pollution naturally. The future perspective presents a great need to produce an ecosystem where microbes, plants, and nanoparticles synergistically control smog. In addition, further advancements would be needed to modify the genetic makeup of microbes and plants. Biotechnological approaches like CRISPR-Cas9 can be applied to the editing and cutting of specific genes responsible for the bioremediation of VOCs, NOx, SOx, and harmful hydrocarbons. The extracted genes can then be expressed in biologically modified microorganisms and plants for the enhanced bioremediation of smog. [ABSTRACT FROM AUTHOR]

This study examines Retrieval-Augmented Generation (RAG) in large language models (LLMs) and their significant application for undertaking systematic literature reviews (SLRs). RAG-based LLMs can potentially automate tasks like data extraction, summarization, and trend identification. However, while LLMs are exceptionally proficient in generating human-like text and interpreting complex linguistic nuances, their dependence on static, pre-trained knowledge can result in inaccuracies and hallucinations. RAG mitigates these limitations by integrating LLMs' generative capabilities with the precision of real-time information retrieval. We review in detail the three key processes of the RAG framework—retrieval, augmentation, and generation. We then discuss applications of RAG-based LLMs to SLR automation and highlight future research topics, including integration of domain-specific LLMs, multimodal data processing and generation, and utilization of multiple retrieval sources. We propose a framework of RAG-based LLMs for automating SRLs, which covers four stages of SLR process: literature search, literature screening, data extraction, and information synthesis. Future research aims to optimize the interaction between LLM selection, training strategies, RAG techniques, and prompt engineering to implement the proposed framework, with particular emphasis on the retrieval of information from individual scientific papers and the integration of these data to produce outputs addressing various aspects such as current status, existing gaps, and emerging trends. [ABSTRACT FROM AUTHOR]

Historically, most insect chronoecological research has used direct observations, cameras or infrared beam‐based monitors to quantify movement across timed intervals. Although some alternative DIY systems are cheaper than the current standard locomotor activity monitor, these options remain complicated to build and/or computationally intensive.We developed the imaging Locomotor Activity Monitor (iLAM), an affordable (~$75 USD/unit) system for activity quantification. The iLAM utilizes a Raspberry Pi Zero W computer and night‐vision camera inside a flight cage to photograph a population of insects at user‐defined intervals. Open‐source, modular R‐scripts process the images and output a file containing the number, size, coordinate location and timestamp of all movements (blobs) identified between consecutive images. Output can be analysed directly or converted into the standard TriKinetics DAM format.We demonstrated the flexibility and power of the iLAM system by comparing diel and circadian activity of different insect species (fireflies: Photinus marginellus, P. greeni, P. obscurellus), ecotypes (moths: Ostrinia nubilalis) and sexes (moths: O. nubilalis). Data captured by only six iLAMs ($450) identified that peak activity of O. nubilalis females (AZT: 19.2 h) occurs significantly earlier than males (22.0 h). Additionally, male moths from a univoltine population exhibited a significantly shorter endogenous period length (AZT: 21.3 h) than males from a bivoltine genetic background (22.7 h).The iLAM will serve as a valuable tool for researchers seeking to measure locomotor activity across diverse species, sexes and populations in constant and changing environments. [ABSTRACT FROM AUTHOR]

Simple Summary: This study extended the use of Track 3D trajectory instruments to investigate the previously unobserved nocturnal activities of Spodoptera frugiperda (Lepidoptera: Noctuidae), a species of moth Noctuidae. The results indicate that flying and wing flapping are the most common activities, with observed flight patterns including parabolic, circular, and zigzag trajectories. Spodoptera frugiperda, also known as the fall armyworm (FAW), is classified by the Food and Agriculture Organization of the United Nations (FAO) as a major agricultural pest. By gaining a more nuanced understanding of the fall armyworm's courtship behavior, simpler and more environmentally friendly methods of controlling this pest can be developed. This study used the Track 3D system to meticulously record and describe the activity characteristics and patterns of adult males and females during courtship. The results show that adult FAWs engaged in a variety of activities during courtship that were either discrete (flying, flapping, moving, and crawling), continuous (flapping + flying, flapping + crawling, and flying + crawling), or combined (flapping + touching + flapping; flying + touching + flying). Flying and flapping were the most common activities, with observed flight patterns consisting of parabolic, circular, and zigzag trajectories. The peak activity times for adult FAWs are mainly concentrated at 11:00 p.m., 3:00 a.m., and 5:00 a.m., providing fundamental data for the precise attraction and control of adult FAWs at later stages. [ABSTRACT FROM AUTHOR]

Background: Respiratory infections refer to any disease of airways and lungs which affects the respiratory system of humans. The nasal cavities, pharynx, larynx, trachea, bronchi and bronchioles, the tissues of the lungs and the respiratory muscles of chest cage are all susceptible to respiratory system diseases. To evaluate cost-benefit and cost-effective analysis of medications used in respiratory tract diseases, an observational prospective study was conducted for 120 patients. Materials and Methods: The patient data and other socioeconomic details were collected. The current index of medical specialists, updated version in March 2022, was used for Cost benefit and Cost effectiveness study. Regression analysis was used for the statistical analysis. Results: Among the 120 participants studied, 74 (61.66%) were male and 46 (38.34%) were female. Out of these participants, 89 had a C/B ratio of less than 1,30 had a C/B ratio greater than 1 and 1 had a C/B ratio equal to 1. The Cost-Effectiveness Analysis (CEA) of various drugs indicated that among bronchodilators, Asthalin is more cost-effective than Duolin; among corticosteroids, Budecort is more cost-effective than Hydrocort; and among anti-tuberculosis medications, AKT-4 is more cost-effective than Ethambutol. Conclusion: The common medications prescribed in our study were Asthalin (bronchodilators). Out of 120 study participants 89 patients were cost benefited from the treatment. The CEA results showed that Asthalin, Budecort and AKT-4 are more cost-effective than Duolin, Hydrocort and Ethambutol. The study found that Asthalin is the most effective treatment for respiratory tract diseases among participants, according to CBA and CEA. [ABSTRACT FROM AUTHOR]