Use of the traditional Chinese medicine "compound healthy ear agent" to protect against age-related hearing loss in mice: A proteomics study.

Background: Previous studies have shown that the traditional Chinese medicine (TCM) called "compound healthy ear agent" (CHEA) had anti-apoptosis effects in cochlear hair cells and spiral ganglion neurons, and could protect mice hearing against presbycusis or age-related hearing loss (AHL), as well as aminoglycoside antibiotic-induced ototoxicity. Because its mechanisms of action are still unclear, we investigated the mechanism of action of CHEA against AHL in mice using proteomics techniques. Methods: Eighteen C57BL/6J mice at 1 month of age were randomly divided into three groups: (A) drinking water until 2 months of age, K2M); (B) drinking water until 7 months of age to induce AHL, K7M; (C) drinking water containing CHEA daily until 7 months of age as treatment group, Z7M. At 2 or 7 months mice were sacrificed and their cochleae were removed for proteomics analysis. Results: The numbers of proteins with a false discovery rate (FDR) < 1% were respectively 5873 for qualitative and 5492 for quantitative statistics. The numbers of proteins with differential enrichment at least 1.5-fold (p < 0.05) were respectively 351 for K7M vs K2M groups, 52 for Z7M vs K7M groups, 264 for Z7M vs K2M groups. The differentially expressed proteins in the Z7M group were involved in synaptic molecular transmission, energy metabolism, immune response, antioxidant defenses, and anti-apoptosis. Conclusion: The TCM CHEA played a protective role against AHL in mice by regulating the expression of specific proteins and genes in cochlear hair cells and spiral ganglion neurons. Besides the pathways expected to be involved (antioxidant and anti-apoptosis), proteins related to immune response is a new finding of the present study.

Melatonin alleviates high temperature exposure induced fetal growth restriction via the gut-placenta-fetus axis in pregnant mice.

INTRODUCTION: Global warming augments the risk of adverse pregnancy outcomes in vulnerable expectant mothers. Pioneering investigations into heat stress (HS) have predominantly centered on its direct impact on reproductive functions, while the potential roles of gut microbiota, despite its significant influence on distant tissues, remain largely unexplored. Our understanding of deleterious mechanisms of HS and the development of effective intervention strategies to mitigate the detrimental impacts are still limited. OBJECTIVES: In this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment. METHODS: We firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment. RESULTS: Melatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS-challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight. CONCLUSION: Melatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.

Kongensin a attenuates intervertebral disc degeneration by inhibiting TAK1-mediated PANoptosis of nucleus pulposus cells.

Low back pain (LBP) is most commonly caused by intervertebral disc degeneration (IVDD). Pyroptosis, apoptosis, and necroptosis are crucial in IVDD pathogenesis; however, possible simultaneous occurrence in IVDD and co-regulation between the pathways and the regulatory mechanisms have not been investigated. PANoptosis is a regulated cell death (RCD) pathway with the key characteristics of pyroptosis, apoptosis, and necroptosis. This study revealed that tert-butyl hydroperoxide (TBHP) altered the expression of key proteins involved in PANoptosis in nucleus pulposus cells (NPCs). Furthermore, the natural product Kongensin A (KA), which has potential anti-necrotic and anti-inflammatory properties, inhibited PANoptosis. TAK1, often referred to as mitogen-activated protein kinase kinase kinase 7 (Map3k7), is a key regulator of innate immunity, cell death, inflammation, and cellular homeostasis; however, the physiological roles and regulatory mechanisms underlying IVDD remain unclear. In this study, we discovered that KA can upregulate TAK1 expression in NPCs, -which inhibits PANoptosis by suppressing oxidative stress. In conclusion, our results suggest that KA inhibits PANoptosis and delays IVDD progression in NPCs by upregulating TAK1 expression to maintain mitochondrial redox balance. Consequently, targeting TAK1 may be a promising therapeutic approach for IVDD therapy.

Dietary supplementation of benzoic acid and essential oils combination enhances intestinal resilience against LPS stimulation in weaned piglets.

BACKGROUND: The benefits of combining benzoic acid and essential oils (BAO) to mitigate intestinal impairment during the weaning process have been well established, while the detailed underlying mechanism has not been fully elucidated. Previous research has primarily focused on the reparative effects of BAO on intestinal injury, while neglecting its potential in enhancing intestinal stress resistance. METHODS: In this study, we investigated the pre-protective effect of BAO against LPS-induced stress using a modified experimental procedure. Piglets were pre-supplemented with BAO for 14 d, followed by a challenge with LPS or saline to collect blood and intestinal samples. RESULTS: Our findings demonstrated that BAO supplementation led to significant improvements in piglets' final weight, average daily gain, and feed intake/body gain ratio. Additionally, BAO supplementation positively influenced the composition of intestinal microbiota, increasing beneficial Actinobacteriota and Alloprevotella while reducing harmful Desulfobacterota, Prevotella and Oscillospira. Furthermore, BAO supplementation effectively mitigated oxidative disturbances and inflammatory responses induced by acute LPS challenge. This was evidenced by elevated levels of T-AOC, SOD, and GSH, as well as decreased levels of MDA, TNF-α, and IL-6 in the plasma. Moreover, piglets subjected to LPS challenge and pre-supplemented with BAO exhibited significant improvements in intestinal morphological structure and enhanced integrity, as indicated by restored expression levels of Occludin and Claudin-1 compared to the non-supplemented counterparts. Further analysis revealed that BAO supplementation enhanced the jejunal antioxidative capacity by increasing GSH-Px levels and decreasing MDA levels under the LPS challenge and stimulated the activation of the Nrf2 signaling pathway. Additionally, the reduction of TLR4/NF-κB/MAPK signaling pathways activation and proinflammatory factor were also observed in the jejunal of those piglets fed with BAO. CONCLUSIONS: In summary, our study demonstrates that pre-supplementation of BAO enhances the anti-stress capacity of weaned piglets by improving intestinal microbiota composition, reinforcing the intestinal barrier, and enhancing antioxidative and anti-inflammatory capabilities. These effects are closely associated with the activation of Nrf2 and TLR4/NF-κB/MAPK signaling pathways.

Activin A marks a novel progenitor cell population during fracture healing and reveals a therapeutic strategy.

Insufficient bone fracture repair represents a major clinical and societal burden and novel strategies are needed to address it. Our data reveal that the transforming growth factor-ß superfamily member Activin A became very abundant during mouse and human bone fracture healing but was minimally detectable in intact bones. Single-cell RNA-sequencing revealed that the Activin A-encoding gene Inhba was highly expressed in a unique, highly proliferative progenitor cell (PPC) population with a myofibroblast character that quickly emerged after fracture and represented the center of a developmental trajectory bifurcation producing cartilage and bone cells within callus. Systemic administration of neutralizing Activin A antibody inhibited bone healing. In contrast, a single recombinant Activin A implantation at fracture site in young and aged mice boosted: PPC numbers; phosphorylated SMAD2 signaling levels; and bone repair and mechanical properties in endochondral and intramembranous healing models. Activin A directly stimulated myofibroblastic differentiation, chondrogenesis and osteogenesis in periosteal mesenchymal progenitor culture. Our data identify a distinct population of Activin A-expressing PPCs central to fracture healing and establish Activin A as a potential new therapeutic tool.

Heat Stress-Induced Fetal Intrauterine Growth Restriction Is Associated with Elevated LPS Levels Along the Maternal Intestine-Placenta-Fetus Axis in Pregnant Mice.

The exacerbation of the greenhouse effect has made heat stress (HS) an important risk factor for the occurrence of intrauterine growth restriction (IUGR). The experiment aims to uncover the effects of maternal HS on IUGR and its mechanisms. The results showed that HS leads to decreased maternal and fetal birth weights, accompanied by increased serum oxidative stress and cortisol levels. Moreover, HS inflicted significant damage to both the intestinal and placental barriers, altering maternal gut microbiota and increasing intestinal LPS levels. As a result, LPS levels increased in maternal serum, placenta, and fetus. Furthermore, HS damaged the intestinal structure, intensifying inflammation and disrupting the redox balance. The placenta exposed to HS exhibited changes in the placental structure along with disrupted angiogenesis and decreased levels of nutritional transporters. Additionally, the leakage of LPS triggered placental JNK and ERK phosphorylation, ultimately inducing severe placental inflammation and oxidative stress. This study suggests that LPS translocation from the maternal intestine to the fetus, due to a disrupted gut microbiota balance and compromised intestinal and placental barrier integrity, may be the primary cause of HS-induced IUGR. Furthermore, increased LPS leakage leads to placental inflammation, redox imbalance, and impaired nutrient transport, further restricting fetal growth.

Single-cell epigenetic, transcriptional, and protein profiling of latent and active HIV-1 reservoir revealed that IKZF3 promotes HIV-1 persistence.

Understanding how HIV-1-infected cells proliferate and persist is key to HIV-1 eradication, but the heterogeneity and rarity of HIV-1-infected cells hamper mechanistic interrogations. Here, we used single-cell DOGMA-seq to simultaneously capture transcription factor accessibility, transcriptome, surface proteins, HIV-1 DNA, and HIV-1 RNA in memory CD4+ T cells from six people living with HIV-1 during viremia and after suppressive antiretroviral therapy. We identified increased transcription factor accessibility in latent HIV-1-infected cells (RORC) and transcriptionally active HIV-1-infected cells (interferon regulatory transcription factor [IRF] and activator protein 1 [AP-1]). A proliferation program (IKZF3, IL21, BIRC5, and MKI67 co-expression) promoted the survival of transcriptionally active HIV-1-infected cells. Both latent and transcriptionally active HIV-1-infected cells had increased IKZF3 (Aiolos) expression. Distinct epigenetic programs drove the heterogeneous cellular states of HIV-1-infected cells: IRF:activation, Eomes:cytotoxic effector differentiation, AP-1:migration, and cell death. Our study revealed the single-cell epigenetic, transcriptional, and protein states of latent and transcriptionally active HIV-1-infected cells and cellular programs promoting HIV-1 persistence.

Single-cell multiomic understanding of HIV-1 reservoir at epigenetic, transcriptional, and protein levels.

PURPOSE OF REVIEW: The success of HIV-1 eradication strategies relies on in-depth understanding of HIV-1-infected cells. However, HIV-1-infected cells are extremely heterogeneous and rare. Single-cell multiomic approaches resolve the heterogeneity and rarity of HIV-1-infected cells. RECENT FINDINGS: Advancement in single-cell multiomic approaches enabled HIV-1 reservoir profiling across the epigenetic (ATAC-seq), transcriptional (RNA-seq), and protein levels (CITE-seq). Using HIV-1 RNA as a surrogate, ECCITE-seq identified enrichment of HIV-1-infected cells in clonally expanded cytotoxic CD4+ T cells. Using HIV-1 DNA PCR-activated microfluidic sorting, FIND-seq captured the bulk transcriptome of HIV-1 DNA+ cells. Using targeted HIV-1 DNA amplification, PheP-seq identified surface protein expression of intact versus defective HIV-1-infected cells. Using ATAC-seq to identify HIV-1 DNA, ASAP-seq captured transcription factor activity and surface protein expression of HIV-1 DNA+ cells. Combining HIV-1 mapping by ATAC-seq and HIV-1 RNA mapping by RNA-seq, DOGMA-seq captured the epigenetic, transcriptional, and surface protein expression of latent and transcriptionally active HIV-1-infected cells. To identify reproducible biological insights and authentic HIV-1-infected cells and avoid false-positive discovery of artifacts, we reviewed current practices of single-cell multiomic experimental design and bioinformatic analysis. SUMMARY: Single-cell multiomic approaches may identify innovative mechanisms of HIV-1 persistence, nominate therapeutic strategies, and accelerate discoveries.

A time-series analysis of short-term ambient ozone exposure and hospitalizations from acute myocardial infarction in Henan, China.

Epidemiological studies in recent years have identified an association between exposure to air pollutants and acute myocardial infarction (AMI); however, the association between short-term ozone (O3) exposure and AMI hospitalization remains unclear, particularly in developing countries. Therefore, this study collected information on 24,489 AMI patients, including daily air pollutant and meteorological data in Henan, China, between 2016 and 2021. A distributed lagged nonlinear model combined with a Poisson regression model was used to estimate the nonlinear lagged effect of O3 on AMI hospitalizations. We also quantified the effects of O3 on the number of AMI hospitalizations, hospitalization days, and hospitalization costs. The results showed that single- and dual-pollution models of O3 at lag0, lag1, and lag (01-07) were risk factors for AMI hospitalizations, with the most significant effect at lag03 (RR = 1.132, 95% CI:1.083-1.182). Further studies showed that males, younger people (15-64 years), warm seasons, and long sunshine duration were more susceptible to O3. Hospitalizations attributable to O3 during the study period accounted for 11.66% of the total hospitalizations, corresponding to 2856 patients, 33,492 hospital days, and 90 million RMB. Maintaining O3 at 10-130 µg/m3 can prevent hundreds of AMI hospitalizations and save millions of RMB per year in Henan, China. In conclusion, we found that short-term exposure to O3 was significantly associated with an increased risk of hospitalization for AMI in Henan, China, and that further reductions in ambient O3 levels may have substantial health and economic benefits for patients and local healthcare facilities.

SrCl2·6H2O: An Alkaline-Earth-Metal Chloride Hexahydrate as Deep-Ultraviolet Nonlinear-Optical Crystal with the {[Sr(H2O)6]2+}∞ Cationic Framework.

Exploring deep-ultraviolet (DUV) nonlinear-optical (NLO) materials is significant for the conversion of high-frequency laser. Herein, two alkali-earth-metal halide hexahydrates, SrX2·6H2O (X = Cl, Br), were obtained, and the centimeter-sized single crystals of SrCl2·6H2O were grown by a slow evaporation method. Both of them crystallize in the trigonal space group P321, and their crystal structures show {[Sr(H2O)6]2+}∞ cationic chains, with isolated Cl- or Br- anions interspersed between the chains. SrCl2·6H2O exhibits a moderate second-harmonic-generation response (0.4 × KDP) at 1064 nm and can realize phase matching. Importantly, SrCl2·6H2O has a short ultraviolet cutoff edge (<200 nm). Crystal growth, crystal structures, optical performances, and theoretical calculations of the title and related compounds have been discussed in this work. This study enriches the understanding of metal halide hydrates as NLO materials in the DUV region.

Echocardiographic evaluation of the effect of dapagliflozin on epicardial adipose tissue and left ventricular systolic function in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Epicardial adipose tissue (EAT) is associated with cardiovascular disease, and sodium-glucose cotransporter-2 inhibitors (SGLT-2I) have been reported to reduce the occurrence of cardiovascular events. This study was designed to investigate the effect of an SGLT-2 inhibitor (dapagliflozin) on EAT and left ventricular (LV) systolic function in type 2 diabetes mellitus (T2DM) patients during a 6-month follow-up. METHODS: Twenty-seven T2DM patients who received dapagliflozin for the first time were enrolled in this study to measure EAT thickness and evaluate LV function before and after 6 months of SGLT-2 administration. The thickness of EAT was measured as the echo-free space between the free wall of the right ventricle and the visceral layer of the pericardium at end-systole by echocardiography. LV systolic function was evaluated by LV global longitudinal strain (LV GLS) obtained through two-dimensional speckle tracking echocardiography (2D-STE) technology. RESULTS: After a 6-month follow-up, twenty-five patients completed this study. The values of EAT thickness, HbA1c, body weight, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were significantly reduced, while the LV GLS value was significantly increased. Moreover, the increase in LV GLS was independently associated with the reduction in EAT thickness, HbA1c, weight, and SBP (all p < 0.05). CONCLUSIONS: Dapagliflozin can reduce EAT thickness and improve LV systolic function in T2DM patients. 2D-STE can be used for the early evaluation of the beneficial effect of dapagliflozin on LV systolic function. The improvement in LV systolic function is independently associated with a reduction in EAT thickness.

5-Heptadecylresorcinol alleviated high-fat diet induced obesity and insulin resistance by activating brown adipose tissue.

The whitening and loss of brown adipose tissue (BAT) during obesity and aging are associated with a higher risk of metabolic syndrome and chronic diseases. 5-Heptadecylresorcinol (AR-C17), the specific biomarker of whole-grain wheat and rye intake, has been proved to have notable health promoting effects, whereas whether AR-C17 could modulate BAT function and the potential mechanism of action remains unclear. In this study, we found that AR-C17 could significantly inhibit body weight gain and insulin resistance in high-fat diet (HFD) induced obese mice. Moreover, AR-C17 treatment improved whole body energy metabolism and alleviated the whitening and loss of BAT compared with the HFD group. RNA sequencing and western-blot analysis indicated that expression of genes and proteins related to BAT energy metabolism was upregulated by AR-C17 administration, including AMPK, UCP-1, ACSL1, CPT1A, and SIRT3. These results suggested that brown adipose tissue might be the target of AR-C17 to prevent obesity and its associated insulin resistance.

A Systematic Review and Meta-Analysis Protocol to Establish How Common Clinical Acupoint Stimulation-Related Therapies Should Be Used for Managing Insomnia.

Background: Many studies have now investigated the effects of common clinical acupoint stimulation-related therapies (ASRTs) following the meridian theory of traditional Chinese medicine for the management of insomnia. However, ASRT choice is currently based on personal clinical experience or patient preference. This study will review the common ASRTs reported in clinical trials and analyze their efficacy and safety for managing insomnia with or without co-morbidities. Methods: English and Chinese databases will be thoroughly searched, and other potentially eligible trials will be obtained by reviewing reference lists of identified studies and previous reviews. Only randomized controlled trials (RCTs) of common clinical ASRTs to manage insomnia published in peer-reviewed journals will be considered. Sleep quality questionnaires or indices will be considered as the main outcome, while the secondary outcomes will include sleep parameters, daytime dysfunction, quality of life, and adverse effects. Two reviewers will independently investigate eligible RCTs, extract information, analyze their methodological quality, and employ Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria to evaluate the strength of the evidence. The treatment impact of various ASRTs will be calculated using meta-analysis techniques, and the degree of study heterogeneity will be assessed using Cochrane's Q and I-squared statistics. Subgroup and sensitivity analyses will be used to evaluate the reliability of the results. Results: Our systematic review and meta-analysis will present up-to-date evidence on: 1) which common clinical ASRTs are beneficial for the management of insomnia; and 2) whether the effects of common clinical ASRTs on insomnia vary depending on clinical, participant, and treatment characteristics. Conclusion: The results of our review should help decision-makers make educated choices regarding evidence-based non-pharmacological management options for insomnia. Study Registration: The International Platform of Registered Systematic Review and Meta-analysis (INPLASY), record INPLASY2021120137.

Comparative efficacy of gait training for balance outcomes in patients with stroke: A systematic review and network meta-analysis.

Background: Growing evidence suggests that gait training can improve stroke patients' balance outcomes. However, it remains unclear which type of gait training is more effective in improving certain types of balance outcomes in patients with stroke. Thus, this network meta-analysis (NMA) included six types of gait training (treadmill, body-weight-supported treadmill, virtual reality gait training, robotic-assisted gait training, overground walking training, and conventional gait training) and four types of balance outcomes (static steady-state balance, dynamic steady-state balance, proactive balance, and balance test batteries), aiming to compare the efficacy of different gait training on specific types of balance outcomes in stroke patients and determine the most effective gait training. Method: We searched PubMed, Embase, Medline, Web of Science, and Cochrane Library databases from inception until 25 April 2022. Randomized controlled trials (RCTs) of gait training for the treatment of balance outcomes after stroke were included. RoB2 was used to assess the risk of bias in the included studies. Frequentist random-effects network meta-analysis (NMA) was used to evaluate the effect of gait training on four categories of balance outcomes. Result: A total of 61 RCTs from 2,551 citations, encompassing 2,328 stroke patients, were included in this study. Pooled results showed that body-weight-support treadmill (SMD = 0.30, 95% CI [0.01, 0.58]) and treadmill (SMD = 0.25, 95% CI [0.00, 0.49]) could improve the dynamic steady-state balance. Virtual reality gait training (SMD = 0.41, 95% CI [0.10, 0.71]) and body-weight-supported treadmill (SMD = 0.41, 95% CI [0.02, 0.80]) demonstrated better effects in improving balance test batteries. However, none of included gait training showed a significant effect on static steady-state balance and proactive balance. Conclusion: Gait training is an effective treatment for improving stroke patients' dynamic steady-state balance and balance test batteries. However, gait training had no significant effect on static steady-state balance and proactive balance. To achieve maximum efficacy, clinicians should consider this evidence when recommending rehabilitation training to stroke patients. Considering body-weight-supported treadmill is not common for chronic stroke patients in clinical practice, the treadmill is recommended for those who want to improve dynamic steady-state balance, and virtual reality gait training is recommended for those who want to improve balance test batteries. Limitation: Missing evidence in relation to some types of gait training is supposed to be taken into consideration. Moreover, we fail to assess reactive balance in this NMA since few included trials reported this outcome. Systematic Review Registration: PROSPERO, identifier CRD42022349965.

Association of traditional Chinese medicine body constitution and cold syndrome with leukocyte mitochondrial functions: An observational study.

Body constitution in traditional Chinese medicine (TCM) refers to the holistic and relatively durable state of an individual, based on the qi and blood assessment, and TCM syndrome is defined as the theoretical abstraction of disease-symptom profiles. The biological basis as related to mitochondria, which produce most of the cellular energy, has not been well studied. This study aimed to elucidate the association of mitochondrial function with TCM body constitution and cold syndrome. Body constitution and cold syndrome in TCM were assessed using the Constitution in Chinese Medicine Questionnaire (CCMQ). The mitochondrial function of peripheral leukocytes was evaluated based on oxygen consumption rate (OCR) and enzyme activity; OCR reflects mitochondrial activity and the capacity to produce adenosine triphosphate (ATP). Cellular adenosine nucleotides and malondialdehyde levels were determined using high-performance liquid chromatography to assess the potential bioenergetic mechanisms. A total of 283 adults participated in this study. Leukocytes from subjects with a balanced constitution had higher OCRs than those with unbalanced constitutions. Yang deficiency and cold syndrome also demonstrated lower energy metabolism, as indicated by reduced basal metabolic rate and cellular levels of ATP and malondialdehyde. Decreased mitochondrial enzyme activity has been observed in individuals with the cold syndrome. Unbalanced body constitutions in TCM impair mitochondrial function in leukocytes, which may contribute to the high disease susceptibility. Cold syndrome is characterized by reduced mitochondrial mass, which may explain its symptoms of low-energy metabolism and cold intolerance.

Physiological and biochemical changes during fruit maturation and ripening in highbush blueberry (Vaccinium corymbosum L.).

The sweetness of blueberry fruit increases over time, as acids are converted to sugars, and full flavor development is formed by harvest. We comprehensively analyzed the changes and correlation in physiological and biochemical characteristics of blueberries at different maturity stages, including texture, quality, taste and energy change. Our analysis revealed that total anthocyanin content increased and firmness decreased as fruit ripened. Percent moisture, titratable acid (TA), chlorophyll and carotenoid content also decreased, while total soluble solids (TSS), pH, TSS/TA ratio, vitamin C, soluble proteins, and ethylene production all increased. Antioxidant enzyme activity gradually increased during ripening but energy-related metabolites decreased. The flavor attributes of sweetness, bitterness, and sourness were readily perceived using an electronic tongue and a total of 76 volatile compounds were detected by GC-MS. In summary, the maturation of blueberries was correlated with increases of anthocyanins, nutrients, antioxidant activity, taste and aroma, but negatively correlated with energy metabolism.

Moderate selenium mitigates hand grip strength impairment associated with elevated blood cadmium and lead levels in middle-aged and elderly individuals: insights from NHANES 2011-2014.

Background: Selenium (Se) has been reported to have an antagonistic effect on heavy metals in animals. Nevertheless, there is a lack of epidemiological research examining whether Se can mitigate the adverse effects of cadmium (Cd) and lead (Pb) on hand grip strength (HGS) in middle-aged and elderly individuals. Methods: This study used data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). HGS measurements were conducted by trained examiners with a dynamometer. Concentrations of Se, Cd, and Pb in blood were determined via inductively coupled plasma mass spectrometry. We employed linear regression, restricted cubic splines, and quantile g-computation (qgcomp) to assess individual and combined associations between heavy metals and HGS. The study also explored the potential influence of Se on these associations. Results: In both individual metal and multi-metal models adjusted for confounders, general linear regression showed Se's positive association with HGS, while Cd and Pb inversely related to it. At varying Se-Cd and Se-Pb concentrations, high Se relative to low Se can attenuate Cd and Pb's HGS impact. An inverted U-shaped correlation exists between Se and both maximum and combined HGS, with Se's benefit plateauing beyond approximately 200 µg/L. Stratified analysis by Se quartiles reveals Cd and Pb's adverse HGS effects diminishing as Se levels increase. Qgcomp regression analysis detected Se alleviating HGS damage from combined Cd and Pb exposure. Subsequent subgroup analyses identified the sensitivity of women, the elderly, and those at risk of diabetes to HGS impairment caused by heavy metals, with moderate Se supplementation beneficial in mitigating this effect. In the population at risk for diabetes, the protective role of Se against heavy metal toxicity-induced HGS reduction is inhibited, suggesting that diabetic individuals should particularly avoid heavy metal-induced handgrip impairment. Conclusion: Blood Cd and Pb levels are negatively correlated with HGS. Se can mitigate this negative impact, but its effectiveness plateaus beyond 200 µg/L. Women, the elderly, and those at risk of diabetes are more vulnerable to HGS damage from heavy metals. While Se supplementation can help, its protective effect is limited in high diabetes risk groups.

Interferon opens up: HIV-induced inflammation reconfigures 3D chromatin conformation and affects where HIV integrates.

Plaza-Jennings et al. applied single-nucleus RNA-seq, sorted neuronal and microglia cells for HiC, and found that chronic HIV infection in the brain induces interferon stimulation in microglia, drives chromatin reconfiguration into a transcriptionally active environment, and changes HIV integration landscape.

Griseofulvin: An Updated Overview of Old and Current Knowledge.

Griseofulvin is an antifungal polyketide metabolite produced mainly by ascomycetes. Since it was commercially introduced in 1959, griseofulvin has been used in treating dermatophyte infections. This fungistatic has gained increasing interest for multifunctional applications in the last decades due to its potential to disrupt mitosis and cell division in human cancer cells and arrest hepatitis C virus replication. In addition to these inhibitory effects, we and others found griseofulvin may enhance ACE2 function, contribute to vascular vasodilation, and improve capillary blood flow. Furthermore, molecular docking analysis revealed that griseofulvin and its derivatives have good binding potential with SARS-CoV-2 main protease, RNA-dependent RNA polymerase (RdRp), and spike protein receptor-binding domain (RBD), suggesting its inhibitory effects on SARS-CoV-2 entry and viral replication. These findings imply the repurposing potentials of the FDA-approved drug griseofulvin in designing and developing novel therapeutic interventions. In this review, we have summarized the available information from its discovery to recent progress in this growing field. Additionally, explored is the possible mechanism leading to rare hepatitis induced by griseofulvin. We found that griseofulvin and its metabolites, including 6-desmethylgriseofulvin (6-DMG) and 4- desmethylgriseofulvin (4-DMG), have favorable interactions with cytokeratin intermediate filament proteins (K8 and K18), ranging from -3.34 to -5.61 kcal mol-1. Therefore, they could be responsible for liver injury and Mallory body (MB) formation in hepatocytes of human, mouse, and rat treated with griseofulvin. Moreover, the stronger binding of griseofulvin to K18 in rodents than in human may explain the observed difference in the severity of hepatitis between rodents and human.

Proteins from Thermophilic Thermus thermophilus Often Do Not Fold Correctly in a Mesophilic Expression System Such as Escherichia coli.

Majority of protein structure studies use Escherichia coli (E. coli) and other model organisms as expression systems for other species' genes. However, protein folding depends on cellular environment factors, such as chaperone proteins, cytoplasmic pH, temperature, and ionic concentrations. Because of differences in these factors, especially temperature and chaperones, native proteins in organisms such as extremophiles may fold improperly when they are expressed in mesophilic model organisms. Here we present a methodology of assessing the effects of using E. coli as the expression system on protein structures. We compare these effects between eight mesophilic bacteria and Thermus thermophilus (T. thermophilus), a thermophile, and found that differences are significantly larger for T. thermophilus. More specifically, helical secondary structures in T. thermophilus proteins are often replaced by coil structures in E. coli. Our results show unique directionality in misfolding when proteins in thermophiles are expressed in mesophiles. This indicates that extremophiles, such as thermophiles, require unique protein expression systems in protein folding studies.