Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury.

JOURNAL/nrgr/04.03/01300535-202505000-00029/figure1/v/2024-07-28T173839Z/r/image-tiff Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties. A the Food and Drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury. A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity, and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar, thus limiting axonal reentry into the host spinal cord. Here we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord injury. We report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders, Schwann cells migrated for considerable distances in both rostral and caudal directions. Such Schwann cell migration led to enhanced axonal regrowth, including the serotonergic and dopaminergic axons originating from supraspinal regions, and promoted recovery of locomotor and urinary bladder functions. Importantly, the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury, even when treatment was delayed for 3 months to mimic chronic spinal cord injury. These findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

Prolonged Microcystis restraint through allelochemicals sustained-release microspheres regulated by carbon material (CM-AC@SM): Optimal formulation, characterization, effects and synergistic inhibition mechanisms.

The Microcystis blooms have caused serious damage to aquatic ecosystems. Microspheres containing allelochemicals with sustained-release properties have the potential to function as a cost-effective and environmentally friendly algaecide against M. aeruginosa. In the current investigation, we successfully optimized the synthesis of allelochemicals sustained-release microspheres regulated by carbon material (CM-AC@SM), which demonstrated a high embedding rate (90.17 %) and loading rate (0.65 %), with an accumulative release rate of 53.27 % on day 30. To investigate the sustained-release mechanism of CM-AC@SM, the sustained-release process of allelochemicals was determined using the Folin-Phenol method and the immersion behavior of the CM-AC@SM was characterized through SEM and XPS. Results showed that allelochemicals were released in the delayed-dissolution mode. In addition, to elucidate the synergistic mechanism of CM-AC@SM towards the inhibition of M. aeruginosa, this study comprehensively assessed the effects of allelochemicals, carbon material and CM-AC@SM on the morphology, antioxidant system activity and photosynthetic activity of M. aeruginosa. The findings indicated that allelochemicals and carbon material induced intracellular protein and nucleic acid leakage by increasing cell membrane permeability, disrupted the extracellular and intracellular morphology of algae, triggered peroxidative damage and restrained antioxidant system activity by stimulating the generation of reactive oxygen species. Simultaneously, the activity of photosystem II was inhibited by allelochemicals and carbon material, substantiated by the reduction in Fv/Fo and Fv/Fm ratios. Hence, CM-AC@SM shows promise in inhibiting M. aeruginosa, offering an efficient approach for the future large-scale control of harmful algal blooms (HABs).

SIRT2 regulates high mobility group protein B1 nucleoplasmic shuttle and degradation via deacetylation in microglia.

High mobility group protein B1 (HMGB1) acts as a pathogenic inflammatory response to mediate ranges of conditions such as epilepsy, septic shock, ischemia, traumatic brain injury, Parkinson's disease, Alzheimer's disease and mass spectrometry. HMGB1 promotes inflammation during sterile and infectious damage and plays a crucial role in disease development. Mobilization from the nucleus to the cytoplasm is the first important step in the release of HMGB1 from activated immune cells. Here, we demonstrated that Sirtuin 2 (SIRT2) physically interacts with and deacetylates HMGB1 at 43 lysine residue at nuclear localization signal locations, strengthening its interaction with HMGB1 and causing HMGB1 to be localized in the cytoplasm. These discoveries are the first to shed light on the SIRT2 nucleoplasmic shuttle, which influences HMGB1 and its degradation, hence revealing novel therapeutic targets and avenues for neuroinflammation treatment.

Bacterial growth and environmental adaptation via thiamine biosynthesis and thiamine-mediated metabolic interactions.

Understanding the ancestral transition from anaerobic to aerobic lifestyles is essential for comprehending life's early evolution. However, the biological adaptations occurring during this crucial transition remain largely unexplored. Thiamine is an important cofactor involved in central carbon metabolism and aerobic respiration. Here, we explored the phylogenetic and global distribution of thiamine-auxotrophic and thiamine-prototrophic bacteria based on the thiamine biosynthetic pathway in 154 838 bacterial genomes. We observed strong coincidences of the origin of thiamine-synthetic bacteria with the "Great Oxygenation Event" (GOE), indicating that thiamine biosynthesis in bacteria emerged as an adaptation to aerobic respiration. Furthermore, we demonstrated that thiamine-mediated metabolic interactions are fundamental factors influencing the assembly and diversity of bacterial communities by a global survey across 4245 soil samples. Through our newly established SIP-metabolic modeling method, we uncovered the active utilization of thiamine-mediated metabolic interactions by bacterial communities in response to changing environments, thus revealing an environmental adaptation strategy employed by bacteria at the community level. Our study demonstrates the widespread thiamine-mediated metabolic interactions in bacterial communities, and their crucial roles in setting the stage for an evolutionary transition from anaerobic to aerobic lifestyles and subsequent environmental adaptation. These findings provide new insights into early bacterial evolution and their subsequent growth and adaptations to environments.

Biodegradation of Cyromazine by Mycobacterium sp. M15: Performance, Degradation Pathways, and Key Enzymes.

Cyromazine, a triazine insecticide, raises food safety concerns due to residues in vegetables like cowpeas. Microbial metabolism is key for pesticide elimination, but bacteria efficient in cyromazine degradation are limited, with uncharacterized enzymes. This study isolated a highly efficient cyromazine-degrading bacterium, Mycobacterium sp. M15, from a cowpea field. M15 utilized cyromazine as the sole carbon source for its growth and completely degraded 0.5 mM cyromazine within 24 h. The degradation pathway involved hydrolyzing cyromazine to N-cyclopropylammeline and further to N-cyclopropylammelide, with amino groups removed sequentially. The cyclopropylamine group in N-cyclopropionamide continued to hydrolyze to cyanuric acid. A protein, CriA, identified as an aminohydrolase in M15, degraded cyromazine to N-cyclopropylammeline. Using CriA reduced cyromazine residues on cowpea surfaces and completely degraded them in immersion solutions. These findings offer insights into cyromazine's microbial degradation mechanism and highlight the potential of cyromazine-degrading enzymes in enhancing food safety.

Lacticaseibacillus rhamnosus inhibits the development of dental caries in rat caries model and in vitro.

OBJECTIVES: Dental caries result from a microbial imbalance in the oral cavity. Probiotics ecologically modulate the oral microflora to prevent caries. This study evaluated the anti-cariogenic effects of two Lacticaseibacillus rhamnosus strains in vitro and in vivo to provide a more theoretical basis for its clinical applications in caries prevention. METHODS: In the study, cariogenic biofilms were grown with L. rhamnosus (LGG) or L. rhamnosus ATCC 7469 and analyzed. Quantitative real-time PCR (qPCR), Scanning Electron Microscope (SEM), and Confocal laser scanning microscope (CLSM) were used to detect the changes in the composition and architectures; cariogenic activity was measured by the lactic acid production and Transverse Microradiography (TMR). The effects of LGG on the 12 Sprague-Dawley rat caries model were assessed using Keyes scores and micro-CT analysis. Oral microbiome changes were evaluated through 16S rRNA gene high-throughput sequencing. RESULTS: L. rhamnosus can reduce cariogenic bacteria in biofilm by 14.7 % to 48.9 %, with LGG exhibiting more potent inhibitory effects. Both strains of L. rhamnosus can adhere to the surface of biofilms, reduce the extracellular polysaccharides (EPS) matrix, and loosen the biofilm structure. L. rhamnosus inhibited cariogenic activity by reducing the lactic acid production in biofilms. The bovine enamel blocks presented lower mineral loss values and lesion depth values in the group Core+L.rh and Core+LGG. LGG-ingested rats had significantly lower levels of moderate dentin lesions and higher mineral density than the control group. The 16 s rRNA gene sequencing revealed that LGG regulated the beta diversity of the oral microbial community in the rat dental caries model. CONCLUSIONS: This study revealed the promising potential of L. rhamnosus, especially the LGG strain, in the ecological prevention of dental caries. CLINICAL SIGNIFICANCE: Probiotics may provide a strategy for preventing caries by regulating the oral microecological balance. The study revealed the promising anti-caries potential of the LGG probiotic strain in vivo and in vitro. It is expected that LGG could be used as an oral probiotic for the clinical prevention and treatment of caries.

Associations of 24-hour movement behaviors with depressive symptoms in rural-dwelling older adults: a compositional data analysis.

BACKGROUND: We aimed to explore the association of sleep duration with depressive symptoms among rural-dwelling older adults in China, and to estimate the impact of substituting sleep with sedentary behavior (SB) and physical activity (PA) on the association with depressive symptoms. METHODS: This population-based cross-sectional study included 2001 rural-dwelling older adults (age ≥ 60 years, 59.2% female). Sleep duration was assessed using the Pittsburgh Sleep Quality Index. We used accelerometers to assess SB and PA, and the 15-item Geriatric Depression Scale to assess depressive symptoms. Data were analyzed using restricted cubic splines, compositional logistic regression, and isotemporal substitution models. RESULTS: Restricted cubic spline curves showed a U-shaped association between daily sleep duration and the likelihood of depressive symptoms (P-nonlinear < 0.001). Among older adults with sleep duration < 7 h/day, reallocating 60 min/day spent on SB and PA to sleep were associated with multivariable-adjusted odds ratio (OR) of 0.81 (95% confidence interval [CI] = 0.78-0.84) and 0.79 (0.76-0.82), respectively, for depressive symptoms. Among older adults with sleep duration ≥ 7 h/day, reallocating 60 min/day spent in sleep to SB and PA, and reallocating 60 min/day spent on SB to PA were associated with multivariable-adjusted OR of 0.78 (0.74-0.84), 0.73 (0.69-0.78), and 0.94 (0.92-0.96), respectively, for depressive symptoms. CONCLUSIONS: Our study reveals a U-shaped association of sleep duration with depressive symptoms in rural older adults and further shows that replacing SB and PA with sleep or vice versa is associated with reduced likelihoods of depressive symptoms depending on sleep duration.

Suicide among patients with oral cancer: A population-based study.

BACKGROUND: Patients with oral cancer usually experience disfigurement and dysfunction which are shared risk factors of suicide. The aim of the study was to comprehensively assess the characteristics of suicide and risk factors for suicide in patients with oral cancer. METHODS: Surveillance, Epidemiology, and End Results database was used to acquire information of patients with common malignant tumors including oral cancer from 1975 to 2020. The aim was to explore the incidence of suicide, and timing of suicide among patients with oral cancer. A Fine-Gray competing risks regression model was employed to analyze risk factors associated with suicide among patients with various demographic and tumor characteristics. RESULTS: Totally, 7685 patients with different malignant tumors committed suicide. Among them, 203 patients with oral cancer died due to suicide, presenting a suicide rate of 54.5/100,000 person-years, which was almost 3.5 times that of the US general population and 1.5 times that of the overall US patients with cancer in our study. Approximately 18 %, 40 %, and 55 % of suicides occurred in first year, first 3 years, and first 5 years after diagnosis. Being male, White race, and having a single primary tumor might be regarded as the risk factors for suicide. CONCLUSION: As oral cavity is closely associated with appearance, pronunciation and ingestion, patients with oral cancer have a significant high risk of suicide. Tremendous attention needs to be paid to patients with oral cancer particularly those exhibiting characteristics associated with a high risk of suicide.

Melatonin targets the paraventricular thalamus to promote non-rapid eye movement sleep in C3H/HeJ mice.

Melatonin (MLT) is an important circadian signal for sleep regulation, but the neural circuitries underlying the sleep-promoting effects of MLT are poorly understood. The paraventricular thalamus (PVT) is a critical thalamic area for wakefulness control and expresses MLT receptors, raising a possibility that PVT neurons may mediate the sleep-promoting effects of MLT. Here, we found that MLT receptors were densely expressed on PVT neurons and exhibited circadian-dependent variations in C3H/HeJ mice. Application of exogenous MLT decreased the excitability of PVT neurons, resulting in hyperpolarization of membrane potential and reduction of action potential firing. MLT also inhibited the spontaneous activity of PVT neurons at both population and single-neuron levels in freely behaving mice. Furthermore, pharmacological manipulations revealed that local infusion of exogeneous MLT into the PVT promoted non-rapid eye movement (NREM) sleep and increased NREM sleep duration, whereas MLT receptor antagonists decreased NREM sleep. Moreover, we found that selectively knocking down endogenous MLT receptors in the PVT decreased NREM sleep and correspondingly increased wakefulness, with particular changes shortly after the onset of the dark or light phase. Taken together, these results demonstrate that PVT is an important target of MLT for promoting NREM sleep.

Novel mRNA adjuvant ImmunER enhances prostate cancer tumor-associated antigen mRNA therapy via augmenting T cell activity.

Prostate cancer (PCa) is characterized as a "cold tumor" with limited immune responses, rendering the tumor resistant to immune checkpoint inhibitors (ICI). Therapeutic messenger RNA (mRNA) vaccines have emerged as a promising strategy to overcome this challenge by enhancing immune reactivity and significantly boosting anti-tumor efficacy. In our study, we synthesized Tetra, an mRNA vaccine mixed with multiple tumor-associated antigens, and ImmunER, an immune-enhancing adjuvant, aiming to induce potent anti-tumor immunity. ImmunER exhibited the capacity to promote dendritic cells (DCs) maturation, enhance DCs migration, and improve antigen presentation at both cellular and animal levels. Moreover, Tetra, in combination with ImmunER, induced a transformation of bone marrow-derived dendritic cells (BMDCs) to cDC1-CCL22 and up-regulated the JAK-STAT1 pathway, promoting the release of IL-12, TNF-α, and other cytokines. This cascade led to enhanced proliferation and activation of T cells, resulting in effective killing of tumor cells. In vivo experiments further revealed that Tetra + ImmunER increased CD8+T cell infiltration and activation in RM-1-PSMA tumor tissues. In summary, our findings underscore the promising potential of the integrated Tetra and ImmunER mRNA-LNP therapy for robust anti-tumor immunity in PCa.

In vivo biological safety investigation of Yb-CALGO femtosecond laser dental surgery.

While lasers have found their successful applications in various clinical specialties, in clinical dental practice, traditional mechanical drills are still predominantly utilized. Although erbium-doped lasers have been demonstrated for dental therapy, their clinical performance is still not satisfactory due to the long pulse width, low peak power, and small repetition rate. To attain a smaller thermal diffusion thus better biological safety and surgical precision, as well as more rapid ablation, the advancement of femtosecond laser techniques has opened another route of dental surgery; however, no biological safety investigation has been reported. Here, we present a systematic study of dental ablation by a Yb:CaAlGdO4 regenerative amplifier with a central wavelength of 1040 nm and pulse width of 160 fs. The in vivo experiment of dental surgery investigating the inflammatory response has been reported, for the first time to the best of our knowledge. It is demonstrated that dental surgery by Yb:CaAlGdO4 femtosecond laser ablation has better biological safety compared to the turbine drilling, thanks to its non-contact and ultrafast heat dissipation nature.

Effect of blood flow restriction training on health promotion in middle-aged and elderly women: a systematic review and meta-analysis.

Background: Physical activities play an important role in alleviating the aging problem and improving the physical fitness of middle-aged and elderly people. Blood flow restriction (BFR) training, also known as pressure training, has been widely used to improve athletes' performance and rehabilitation, which is a relatively novel exercise method for improving the physical fitness of middle-aged and elderly people. The purpose of this study is to conduct a systematic review and meta-analysis of domestic and foreign randomized controlled trial studies on BFR training for middle-aged and elderly women, further explore the impact of BFR training on health status. Methods: Meta-analysis was performed according to PRISMA standards, and charts were drawn using Review Manager 5.4 and Stata 17 software. In this study, the keywords such as "pressure training", "blood restriction training", "elderly women", "KAATSU", "blood flow restriction training" were used on CNKI, China Science and Technology Journal Database, PubMed, Embase, Web of Science, Cochrane Library, EBSCO, Scopus, and randomized controlled trials were searched in all languages. The search was performed from the establishment of database to 2 January 2024. The results of the combined effect were represented by standard mean differences. Results: Among the 681 literature retrieved, six eligible English articles were included in this meta-analysis. The overall effect test of the combined effect was performed on 10 groups of data, and the results were SMD = -0.18 (95%CI: -0.91 to 0.56; p > 0.05), the maximum dynamic force of 1RM SMD = 0.97 (95%CI: 0.35 to 1.58; p < 0.05), leg compression force SMD = -0.10 (95%CI: -0.78 to 0.57; p > 0.05), heart rate SMD = 0.33 (95%CI: -2.50 to 3.17; p > 0.05), systolic blood pressure (SBP) SMD = -1.44 (95%CI: -2.17 to -0.70; p < 0.05), diastolic blood pressure (DBP) SMD = -0.69 (95%CI: 2.54 to 1.15; p > 0.05). Conclusion: BFR training had a significant effect on the increase of the maximum dynamic force of 1RM and decrease of blood pressure in middle-aged and elderly women, but there was no significant difference found in heart rate and leg compression force. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024491642.

Antimicrobial susceptibilities, resistance mechanisms and molecular characteristics of toxigenic Clostridioides difficile isolates in a large teaching hospital in Chongqing, China.

OBJECTIVES: Clostridioides difficile ranks among the primary sources of healthcare-related infections and diarrhoea in numerous nations. We evaluated the drug susceptibility and resistance mechanisms of C. difficile isolates from a hospital in Chongqing, China, and identified resistance rates and resistance mechanisms that differed from previous findings. METHODS: The toxin genes and drug resistance genes of clinical strains were detected using Polymerase Chain Reaction (PCR), and these strains were subjected to Multilocus Sequence Typing (MLST). The agar dilution technique was employed for assessing susceptibility of antibiotics. Clinical data collection was completed through a review of electronic medical records. RESULTS: A total of 67 strains of toxin-producing C. difficile were detected. All C. difficile isolates demonstrated susceptibility to both metronidazole and vancomycin. However, resistance was observed in 8.95%, 16.42%, 56.72%, 56.72%, 31.34% and 5.97% of the isolates for tigecycline, tetracycline, clindamycin, erythromycin, moxifloxacin and rifampin, respectively. Among the strains with toxin genotypes A + B + CDT - and belonging to the ST3, six strains exhibited reduced susceptibility to tigecycline (MIC=0.5mg/L) and tetracycline (MIC=8mg/L). The tetA(P) and tetB(P) genes were present in these six strains, but were absent in tetracycline-resistant strains. Resistance genes (ermB, tetM, tetA(P) and tetB(P)) and mutations (in gyrA, gyrB, and rpoB) were identified in resistant strains. CONCLUSIONS: In contrast to prior studies, we found higher proportions of ST3 isolates with decreased tigecycline sensitivity, sharing similar resistance patterns and resistance genes. In the resistance process of tigecycline and tetracycline, the tetA(P) and tetB(P) genes may play a weak role.

Au24Cd Nanoenzyme Coating for Enhancing Electrochemical Sensing Performance of Metal Wire Microelectrodes.

Dopamine (DA), ascorbic acid (AA), and uric acid (UA) are crucial neurochemicals, and their abnormal levels are involved in various neurological disorders. While electrodes for their detection have been developed, achieving the sensitivity required for in vivo applications remains a challenge. In this study, we proposed a synthetic Au24Cd nanoenzyme (ACNE) that significantly enhanced the electrochemical performance of metal electrodes. ACNE-modified electrodes demonstrated a remarkable 10-fold reduction in impedance compared to silver microelectrodes. Furthermore, we validated their excellent electrocatalytic activity and sensitivity using five electrochemical detection methods, including cyclic voltammetry, differential pulse voltammetry, square-wave pulse voltammetry, normal pulse voltammetry, and linear scanning voltammetry. Importantly, the stability of gold microelectrodes (Au MEs) modified with ACNEs was significantly improved, exhibiting a 30-fold enhancement compared to Au MEs. This improved performance suggests that ACNE functionalization holds great promise for developing micro-biosensors with enhanced sensitivity and stability for detecting small molecules.

[Knock-down of long noncoding RNA H19 (lncRNA H19) promotes human colorectal cell autophagy and inhibits cell apoptosis induced by lipopolysaccharide].

Objective To investigate the expression levels of lncRNA H19 in ulcerative colitis (UC) patients and its role in UC. Methods Colonic mucosa and serum samples were collected from 25 UC patients and 25 healthy individuals at the General Hospital of Xizang Military Region. The expression levels of lncRNA H19 were detected, and the receiver operating characteristic (ROC) curve analysis was performed using serum samples. An in vitro inflammatory model was established in HT29 colorectal cells under lipopolysaccharide (LPS) stimulation, and the expression levels of lncRNA H19 were observed in HT29 cells through fluorescence quantitative PCR. HT29 cells with downregulated lncRNA H19 was constructed using lentivirus-mediated shRNA. The effect of lncRNA H19 on cell survival was analyzed through MTT assay. Cell apoptosis was detected by flow cytometry, and the protein expression levels of apoptosis and autophagy markers were analyzed through Western blot. After treatment with rapamycin, the survival of HT29 cells was observed by MTT assay. Results lncRNA H19 was highly expressed in the colonic mucosa and serum samples of UC patients with the ROC area being 0.786. Following LPS stimulation, the expression levels of lncRNA H19 was significantly increased in a time-dependent manner. Downregulation of lncRNA H19 can promote cell survival, inhibit cell apoptosis and increase autophagy level in HT29 cells. Treatment with rapamycin significantly increased the cell survival rate. Conclusion Knock-down of lncRNA H19 increases autophagy levels, inhibits LPS-induced apoptosis and promotes the survival of colon cells.

Mtnr1b deletion disrupts placental angiogenesis through the VEGF signaling pathway leading to fetal growth restriction.

The placenta, as a "transit station" between mother and fetus, has functions delivering nutrients, excreting metabolic wastes and secreting hormones. A healthy placenta is essential for fetal growth and development while the melatonergic system seems to play a critical physiological role in this organ since melatonin, its synthetic enzymes and receptors are present in the placenta. In current study, Mtnr1a and Mtnr1b knockout mice were constructed to explore the potential roles of melatonergic system played on the placental function and intrauterine growth retardation (IUGR). The result showed that Mtnr1a knockout had little effect on placental function while Mtnr1b knockout reduced placental efficiency and increased IUGR. Considering the extremely high incidence of IURG in sows, the pregnant sows were treated with melatonin. This treatment reduced the incidence of IUGR. All the evidence suggests that the intact melatonergic system in placenta is required for its function. Mechanistical studies uncovered that Mtnr1b knockout increased placental oxidative stress and apoptosis but reduced the angiogenesis. The RNA sequencing combined with histochemistry study identified the reduced angiogenesis and placental vascular density in Mtnr1b knockout mice. These alterations were mediated by the disrupted STAT3/VEGFR2/PI3K/AKT pathway, i.e., Mtnr1b knockout reduced the phosphorylation of STAT3 which is the promotor of VEGFR2. The downregulated VEGFR2 and its downstream elements of PI3K and AKT expressions, then, jeopardizes the angiogenesis and placental development.

Breaking barriers: Innovative approaches for skin delivery of RNA therapeutics.

RNA therapeutics represent a rapidly expanding platform with game-changing prospects in personalized medicine. The disruptive potential of this technology will overhaul the standard of care with reference to both primary and specialty care. To date, RNA therapeutics have mostly been delivered parenterally via injection, but topical administration followed by intradermal or transdermal delivery represents an attractive method that is convenient to patients and minimally invasive. The skin barrier, particularly the lipid-rich stratum corneum, presents a significant hurdle to the uptake of large, charged oligonucleotide drugs. Therapeutic oligonucleotides need to be engineered for stability and specificity and formulated with state-of-the-art delivery strategies for efficient uptake. This review will cover various passive and active strategies deployed to enhance permeation through the stratum corneum and achieve effective delivery of RNA therapeutics to treat both local skin disorders and systemic diseases. Some strategies to achieve selectivity between local and systemic administration will also be discussed.

Scattering approaches to unravel protein solution behaviors in ionic liquids and deep eutectic solvents: From basic principles to recent developments.

Proteins in ionic liquids (ILs) and deep eutectic solvents (DESs) have gained significant attention due to their potential applications in various fields, including biocatalysis, bioseparation, biomolecular delivery, and structural biology. Scattering approaches including dynamic light scattering (DLS) and small-angle X-ray and neutron scattering (SAXS and SANS) have been used to understand the solution behavior of proteins at the nanoscale and microscale. This review provides a thorough exploration of the application of these scattering techniques to elucidate protein properties in ILs and DESs. Specifically, the review begins with the theoretical foundations of the relevant scattering approaches and describes the essential solvent properties of ILs and DESs linked to scattering such as refractive index, scattering length density, ion-pairs, liquid nanostructure, solvent aggregation, and specific ion effects. Next, a detailed introduction is provided on protein properties such as type, concentration, size, flexibility and structure as observed through scattering methodologies. This is followed by a review of the literature on the use of scattering for proteins in ILs and DESs. It is highlighted that enhanced data analysis and modeling tools are necessary for assessing protein flexibility and structure, and for understanding protein hydration, aggregation and specific ion effects. It is also noted that complementary approaches are recommended for comprehensively understanding the behavior of proteins in solution due to the complex interplay of factors, including ion-binding, dynamic hydration, intermolecular interactions, and specific ion effects. Finally, the challenges and potential research directions for this field are proposed, including experimental design, data analysis approaches, and supporting methods to obtain fundamental understandings of complex protein behavior and protein systems in solution. We envisage that this review will support further studies of protein interface science, and in particular studies on solvent and ion effects on proteins.

Clinical characteristics and treatment compounds of obesity-related kidney injury.

Disorders in energy homeostasis can lead to various metabolic diseases, particularly obesity. The obesity epidemic has led to an increased incidence of obesity-related nephropathy (ORN), a distinct entity characterized by proteinuria, glomerulomegaly, progressive glomerulosclerosis, and renal function decline. Obesity and its associated renal damage are common in clinical practice, and their incidence is increasing and attracting great attention. There is a great need to identify safe and effective therapeutic modalities, and therapeutics using chemical compounds and natural products are receiving increasing attention. However, the summary is lacking about the specific effects and mechanisms of action of compounds in the treatment of ORN. In this review, we summarize the important clinical features and compound treatment strategies for obesity and obesity-induced kidney injury. We also summarize the pathologic and clinical features of ORN as well as its pathogenesis and potential therapeutics targeting renal inflammation, oxidative stress, insulin resistance, fibrosis, kidney lipid accumulation, and dysregulated autophagy. In addition, detailed information on natural and synthetic compounds used for the treatment of obesity-related kidney disease is summarized. The synthesis of detailed information aims to contribute to a deeper understanding of the clinical treatment modalities for obesity-related kidney diseases, fostering the anticipation of novel insights in this domain.

Effects of vitamin D3 supplementation on strength of lower and upper extremities in athletes: an updated systematic review and meta-analysis of randomized controlled trials.

Background: Coaches and athletes are increasingly interested in understanding athletes' serum vitamin D levels, their impact on strength, physical performance, and athletic outcomes. Previous meta-analyses were reported with limited sample size and no significant overall effect was found. Hence, it is crucial to conduct a thorough and up-to-date systematic examination and meta-analysis to elucidate the potential advantages of supplementing with vitamin D3 in enhancing muscle strength for athletes. Methods: We performed a thorough investigation, spanning three databases (PubMed, EBSCO, and Cochrane Library), seeking randomized controlled trials (RCTs) in all languages. These trials delved into the influence of vitamin D3 supplementation on the changes of pre- and post-intervention muscle strength in healthy athletes. Our systematic examination and meta-analysis took into account serum 25(OH)D levels exceeding 30 ng/mL as a marker of adequacy. Results: Ten RCTs, comprising 354 athletes (185 in the vitamin D3 group and 169 in the placebo group), fulfilled the inclusion criteria. During the study, 36 athletes were lost to follow-up, leaving 318 athletes (166 in the vitamin D3 group and 152 in the placebo group) with documented complete results. In comparison with the placebo group, there is a significant increase between the changes of pre- and post-intervention serum 25(OH)D levels among athletes following a period of vitamin D3 supplementation (MD 14.76, 95% CI: 8.74 to 20.77, p < 0.0001). Overall effect of four strength measurements including handgrip, one repetition maximum Bench Press (1-RM BP), vertical jump, and quadriceps contraction was not significantly improved (SMD 0.18, 95% CI: -0.02 to 0.37, p = 0.08), but there was a significant increase in quadriceps contraction (SMD 0.57, 95% CI: 0.04 to 1.11, p = 0.04). Conclusion: This updated meta-analysis indicates the potential benefits of vitamin D supplementation for enhancing muscle strength in athletes when analyzing its quantitatively synthesized effects. With limited available studies for the quantitative synthesis, it cannot warrant significant overall enhancements in muscle strength when athletes attain adequate serum 25(OH)D levels through supplementation.