A thalamic-primary auditory cortex circuit mediates resilience to stress.

Resilience enables mental elasticity in individuals when rebounding from adversity. In this study, we identified a microcircuit and relevant molecular adaptations that play a role in natural resilience. We found that activation of parvalbumin (PV) interneurons in the primary auditory cortex (A1) by thalamic inputs from the ipsilateral medial geniculate body (MG) is essential for resilience in mice exposed to chronic social defeat stress. Early attacks during chronic social defeat stress induced short-term hyperpolarizations of MG neurons projecting to the A1 (MGA1 neurons) in resilient mice. In addition, this temporal neural plasticity of MGA1 neurons initiated synaptogenesis onto thalamic PV neurons via presynaptic BDNF-TrkB signaling in subsequent stress responses. Moreover, optogenetic mimicking of the short-term hyperpolarization of MGA1 neurons, rather than merely activating MGA1 neurons, elicited innate resilience mechanisms in response to stress and achieved sustained antidepressant-like effects in multiple animal models, representing a new strategy for targeted neuromodulation.

Mechanosensing by Vascular Endothelium.

Mechanical forces influence different cell types in our bodies. Among the earliest forces experienced in mammals is blood movement in the vascular system. Blood flow starts at the embryonic stage and ceases when the heart stops. Blood flow exposes endothelial cells (ECs) that line all blood vessels to hemodynamic forces. ECs detect these mechanical forces (mechanosensing) through mechanosensors, thus triggering physiological responses such as changes in vascular diameter. In this review, we focus on endothelial mechanosensing and on how different ion channels, receptors, and membrane structures detect forces and mediate intricate mechanotransduction responses. We further highlight that these responses often reflect collaborative efforts involving several mechanosensors and mechanotransducers. We close with a consideration of current knowledge regarding the dysregulation of endothelial mechanosensing during disease. Because hemodynamic disruptions are hallmarks of cardiovascular disease, studying endothelial mechanosensing holds great promise for advancing our understanding of vascular physiology and pathophysiology.

Contribution of copy number variations to education, socioeconomic status and cognition from a genome-wide study of 305,401 subjects.

Educational attainment (EA), socioeconomic status (SES) and cognition are phenotypically and genetically linked to health outcomes. However, the role of copy number variations (CNVs) in influencing EA/SES/cognition remains unclear. Using a large-scale (n = 305,401) genome-wide CNV-level association analysis, we discovered 33 CNV loci significantly associated with EA/SES/cognition, 20 of which were novel (deletions at 2p22.2, 2p16.2, 2p12, 3p25.3, 4p15.2, 5p15.33, 5q21.1, 8p21.3, 9p21.1, 11p14.3, 13q12.13, 17q21.31, and 20q13.33, as well as duplications at 3q12.2, 3q23, 7p22.3, 8p23.1, 8p23.2, 17q12 (105 kb), and 19q13.32). The genes identified in gene-level tests were enriched in biological pathways such as neurodegeneration, telomere maintenance and axon guidance. Phenome-wide association studies further identified novel associations of EA/SES/cognition-associated CNVs with mental and physical diseases, such as 6q27 duplication with upper respiratory disease and 17q12 (105 kb) duplication with mood disorders. Our findings provide a genome-wide CNV profile for EA/SES/cognition and bridge their connections to health. The expanded candidate CNVs database and the residing genes would be a valuable resource for future studies aimed at uncovering the biological mechanisms underlying cognitive function and related clinical phenotypes.

Role of the GalNAc-galectin pathway in the healing of premature rupture of membranes.

BACKGROUND: Premature rupture of the membranes (PROM) is a key cause of preterm birth and represents a major cause of neonatal mortality and morbidity. Natural products N-acetyl-d-galactosamine (GalNAc), which are basic building blocks of important polysaccharides in biological cells or tissues, such as chitin, glycoproteins, and glycolipids, may improve possible effects of wound healing. METHODS: An in vitro inflammation and oxidative stress model was constructed using tumor necrosis-α (TNF-α) and lipopolysaccharide (LPS) action on WISH cells. Human amniotic epithelial cells (hAECs) were primarily cultured by digestion to construct a wound model. The effects of GalNAc on anti-inflammatory and anti-oxidative stress, migration and proliferation, epithelial-mesenchymal transition (EMT), glycosaminoglycan (GAG)/hyaluronic acid (HA) production, and protein kinase B (Akt) pathway in hAECs and WISH cells were analyzed using the DCFH-DA fluorescent probe, ELISA, CCK-8, scratch, transwell migration, and western blot to determine the mechanism by which GalNAc promotes amniotic wound healing. RESULTS: GalNAc decreased IL-6 expression in TNF-α-stimulated WISH cells and ROS expression in LPS-stimulated WISH cells (P < 0.05). GalNAc promoted the expression of Gal-1 and Gal-3 with anti-inflammatory and anti-oxidative stress effects. GalNAc promoted the migration of hAECs (50% vs. 80%) and WISH cells through the Akt signaling pathway, EMT reached the point of promoting fetal membrane healing, and GalNAc did not affect the activity of hAECs and WISH cells (P > 0.05). GalNAc upregulated the expression of sGAG in WISH cells (P < 0.05) but did not affect HA levels (P > 0.05). CONCLUSIONS: GalNAc might be a potential target for the prevention and treatment of PROM through the galectin pathway, including (i) inflammation; (ii) epithelial-mesenchymal transition; (iii) proliferation and migration; and (iv) regression, remodeling, and healing.

Combining transcriptome and metabolome analysis to understand the response of sorghum to Melanaphis sacchari.

BACKGROUND: The sorghum aphid Melanaphis sacchari (Zehntner) (Homoptera: Aphididae) is an important insect in the late growth phase of sorghum (Sorghum bicolor L.). However, the mechanisms of sorghum response to aphid infestation are unclear. RESULTS: In this paper, the mechanisms of aphid resistance in different types of sorghum varieties were revealed by studying the epidermal cell structure and performing a transcriptome and metabolome association analysis of aphid-resistant and aphid-susceptible varieties. The epidermal cell results showed that the resistance of sorghum to aphids was positively correlated with epidermal cell regularity and negatively correlated with the intercellular space and leaf thickness. Transcriptome and metabolomic analyses showed that differentially expressed genes in the resistant variety HN16 and susceptible variety BTX623 were mainly enriched in the flavonoid biosynthesis pathway and differentially expressed metabolites were mainly related to isoflavonoid biosynthesis and flavonoid biosynthesis. The q-PCR results of key genes were consistent with the transcriptome expression results. Meanwhile, the metabolome test results showed that after aphidinfestation, naringenin and genistein were significantly upregulated in the aphid-resistant variety HN16 and aphid-susceptible variety BTX623 while luteolin was only significantly upregulated in BTX623. These results show that naringenin, genistein, and luteolin play important roles in plant resistance to aphid infestation. The results of exogenous spraying tests showed that a 1‰ concentration of naringenin and genistein is optimal for improving sorghum resistance to aphid feeding. CONCLUSIONS: In summary, the physical properties of the sorghum leaf structure related to aphid resistance were studied to provide a reference for the breeding of aphid-resistant varieties. The flavonoid biosynthesis pathway plays an important role in the response of sorghum aphids and represents an important basis for the biological control of these pests. The results of the spraying experiment provide insights for developing anti-aphid substances in the future.

N-Containing Na2VTi(PO4)3/C for Aqueous Sodium-Ion Batteries.

Phosphates featuring a 3D framework offer a promising alternative to aqueous sodium-ion batteries, known for their safety, cost-effectiveness, scalability, high power density, and tolerance to mishandling. Nevertheless, they often suffer from poor reversible capacity stemming from limited redox couples. Herein, N-containing Na2VTi(PO4)3 is synthesized for aqueous sodium-ion storage through multi-electron redox reactions. It demonstrates a capacity of 155.2 mAh g-1 at 1 A g-1 (≈ 5.3 C) and delivers an ultrahigh specific energy of 55.9 Wh kg-1 in a symmetric aqueous sodium-ion battery. The results from in situ X-ray diffraction analysis, ex situ X-ray photoelectron spectroscopy analysis, and first-principle calculations provide insights into the local chemical environment of sodium ions, the mechanisms underlying capacity decay during cycling, and the dynamics of ion and electron transfer at various states of charge. This understanding will contribute to the advancement of electrode materials for aqueous sodium-ion batteries.

Epicardial adipose tissue volume and density are associated with heart failure with improved ejection fraction.

BACKGROUND: Heart failure (HF) with improved ejection fraction (EF, HFimpEF) is a distinct HF subtype, characterized by left ventricular (LV) reverse remodeling and myocardial functional recovery. Multiple cardiometabolic factors are implicated in this process. Epicardial adipose tissue (EAT), emerging as an endocrine and paracrine organ, contributes to the onset and progression of HF. However, the relation between EAT and the incidence of HFimpEF is still unclear. METHODS: A total of 203 hospitalized HF patients with reduced EF (HFrEF, LVEF ≤ 40%) who underwent coronary CT angiography (CCTA) during index hospitalization were consecutively enrolled between November 2011 and December 2022. Routine follow-up and repeat echocardiograms were performed. The incidence of HFimpEF was defined as (1) an absolute LVEF improvement ≥ 10% and (2) a second LVEF > 40% (at least 3 months apart). EAT volume and density were semiautomatically quantified on non-enhanced series of CCTA scans. RESULTS: During a median follow-up of 8.6 (4.9 ~ 13.3) months, 104 (51.2%) patients developed HFimpEF. Compared with HFrEF patients, HFimpEF patients had lower EAT volume (115.36 [IQR 87.08 ~ 154.78] mL vs. 169.67 [IQR 137.22 ~ 218.89] mL, P < 0.001) and higher EAT density (-74.92 ± 6.84 HU vs. -78.76 ± 6.28 HU, P < 0.001). Multivariate analysis showed lower EAT volume (OR: 0.885 [95%CI 0.822 ~ 0.947]) and higher density (OR: 1.845 [95%CI 1.023 ~ 3.437]) were both independently associated with the incidence of HFimpEF. Subgroup analysis revealed that the association between EAT properties and HFimpEF was not modified by HF etiology. CONCLUSIONS: This study reveals that lower EAT volume and higher EAT density are associated with development of HFimpEF. Therapies targeted at reducing EAT quantity and improving its quality might provide favorable effects on myocardial recovery in HF patients.

USP5 facilitates bladder cancer progression by stabilizing the c-Jun protein.

BACKGROUND: Bladder cancer is the second most common genitourinary malignancy worldwide. The death rate of bladder cancer has increased every year. However, the molecular mechanism of bladder cancer is not sufficiently studied. Deubiquitinating enzymes (DUBs) play an important role in carcinogenesis. Several studies have demonstrated that USP5 associated with malignancy and pathological progression in hepatocellular carcinoma, colorectal and non-small cell lung cancer. However, the role of USP5 in bladder cancer need to be explored. METHODS: The USP5 expression was analysed using the web server GEPIA. To explore USP5 function in bladder cancer, we constructed USP5-knockout cell lines in T24 cells. A FLAG-USP5 (WT USP5) plasmid and a plasmid FLAG-USP5 C335A (catalytic-inactive mutant) used to overexpress USP5 in EJ cells. CCK8, colony formation, transwell and scratch assays were used to assess cell viability, proliferation and migration. RNA sequencing (RNA-seq) and dual-luciferase reporter assays were performed to screen the pathway. Coimmunoprecipitation and immunofluorescence were used to explore the interaction between USP5 and c-Jun. Cycloheximide (CHX) chase assays were performed to establish the effect of USP5 on c-Jun stability. Xenograft mouse model was used to study the role of USP5 in bladder cancer. RESULTS: USP5 expression is increased in bladder cancer patients. Genetic ablation of USP5 markedly inhibited bladder cancer cell proliferation, viability, and migration both in vitro and in vivo. RNA-seq and luciferase pathway screening showed that USP5 activated JNK signalling, and we identified the interaction between USP5 and c-Jun. USP5 was found to activate c-Jun by inhibiting its ubiquitination. CONCLUSIONS: Our results show that high USP5 expression promotes bladder cancer progression by stabilizing c-Jun and that USP5 is a potential therapeutic target in bladder cancer.

Evidence of an excitatory purinergic innervation in mouse corpus cavernosum smooth muscle.

BACKGROUND: Evidence suggests that the corpus cavernosum smooth muscle (CCSM) cells of several species, including humans, express purinergic P2X receptors, but it is not known if the corpus cavernosum has an excitatory purinergic innervation. AIM: In this study we aimed to determine if the mouse CCSM has a functional purinergic innervation. METHODS: Mouse CCSM myocytes were enzymatically isolated and studied using the perforated patch configuration of the patch clamp technique. Isometric tension was measured in whole cavernosum tissue subjected to electrical field stimulation (EFS) to evoke nerve-mediated responses. OUTCOMES: The mouse CCSM myocytes expressed P2X1 receptors, and adenosine triphosphate (ATP) evoked inward currents in these cells. In addition, P2X1-mediated contractions were recorded in whole tissue in response to EFS. RESULTS: In cells held under a voltage clamp at -60 mV, ATP (1 µm) evoked large inward currents (mean approximately 900 pA). This current rapidly declined but was repeatable at 8-minute intervals. α,ß-methylene ATP (10 µM), an agonist of P2X1 and P2X3 receptors, caused a similar current that also rapidly declined. Desensitization to α,ß-methylene ATP negated the effect of ATP, but the ATP effect was restored 8 minutes after washout of α,ß-methylene ATP. The effect of ATP was reversibly blocked by NF449 (1 µm), a selective antagonist of P2X1 receptors. In isometric tension experiments electrical field stimulation (EFS) at 0.5-8 Hz evoked frequency-dependent contractions in the presence of l-nitro arginine (l-NO-Arg) (100 µm). When phentolamine (3 µm) and atropine (1 µm) were applied, there remained a nonadrenergic, noncholinergic component of the response to EFS, consisting mainly of a transient contraction. This was significantly reduced by NF449 (1 µm). Finally, in immunocytochemistry experiments, isolated CCSM myocytes stained positively when exposed to an antibody raised against P2X1 receptors. CLINICAL IMPLICATIONS: Previous studies have shown that P2X1 receptors in CCSM are upregulated in diabetes. These findings, taken together with the functional evidence presented here, indicate that P2X1 receptors may provide an alternative therapeutic target for treatment of erectile dysfunction in patients with diabetes, which is known to be relatively resistant to treatment with phosphodiesterase 5 inhibitors. STRENGTHS AND LIMITATIONS: Strengths of this study are the use of a combination of functional experiments (patch clamp) and immunocytochemical analyses to show expression of P2X1 receptors on CCSM myocytes while also performing functional experiments to show that stimulation these receptors results in contraction of CCSM. A limitation of this study was the use of animal rather than human tissue. CONCLUSION: This investigation provides evidence that mouse corpus cavernosum smooth muscle cells express P2X1 receptors and that these receptors are involved in mediating part of the contractile response to nerve stimulation evoked by EFS.

Novel ratio-expressions of genes enables estimation of wound age in contused skeletal muscle.

Given that combination with multiple biomarkers may well raise the predictive value of wound age, it appears critically essential to identify new features under the limited cost. For this purpose, the present study explored whether the gene expression ratios provide unique time information as an additional indicator for wound age estimation not requiring the detection of new biomarkers and allowing full use of the available data. The expression levels of four wound-healing genes (Arid5a, Ier3, Stom, and Lcp1) were detected by real-time polymerase chain reaction, and a total of six expression ratios were calculated among these four genes. The results showed that the expression levels of four genes and six ratios of expression changed time-dependent during wound repair. The six expression ratios provided additional temporal information, distinct from the four genes analyzed separately by principal component analysis. The overall performance metrics for cross-validation and external validation of four typical prediction models were improved when six ratios of expression were added as additional input variables. Overall, expression ratios among genes provide temporal information and have excellent potential as predictive markers for wound age estimation. Combining the expression levels of genes with ratio-expression of genes may allow for more accurate estimates of the time of injury.

The Shear-Accelerated II-I Phase Transition of Isotactic Poly(1-Butene).

The II-I phase transition of isotactic poly(1-butene) (iPBu) leads to improved mechanical performance. However, this will take several weeks and increase storage and processing costs. In this work, shear forces are introduced into the supercooled iPBu melt, and the effects of isothermal crystallization temperature (Tc) and shear temperature (Tshear) on crystallization and phase transition are explored. Shear-induced transcrystalline morphology of Form II with a significantly shortened crystallization induction period can be observed at relatively high Tc (105 °C). Besides, the shear-induced Form II can transit to Form I faster than the unsheared one. In addition, the phase transition rate increases as the Tshear decreases, with the fastest rate occurring at Tshear of 120 °C. The half transition time (t1/2) is measured as 6.3 h when Tc = 105 °C, Tshear = 120 °C, which is much shorter than the 20.7 h required for unsheared samples. The accelerated phase transition of iPBu can be attributed to the stretching of molecular chains, resulting from shear treatment. This study provides a quantitative analysis of the influence of the shear treatment and the Tshear on the II-I phase transition rate. It also presents a cost-effective and straightforward approach for expediting the phase transition process.

Fish skin mucosal surface becomes a barrier of antibiotic resistance genes under apramycin exposure.

Antibiotic resistance genes (ARGs) are a kind of emerging environmental contamination, and are commonly found in antibiotic application situations, attracting wide attention. Fish skin mucosal surface (SMS), as the contact interface between fish and water, is the first line of defense against external pollutant invasion. Antibiotics are widely used in aquaculture, and SMS may be exposed to antibiotics. However, what happens to SMS when antibiotics are applied, and whether ARGs are enriched in SMS are not clear. In this study, Zebrafish (Danio rerio) were exposed to antibiotic and antibiotic resistant bacteria in the laboratory to simulate the aquaculture situation, and the effects of SMS on the spread of ARGs were explored. The results showed that SMS maintained the stability of the bacterial abundance and diversity under apramycin (APR) and bacterial exposure effectively. Until 11 days after stopping APR exposure, the abundance of ARGs in SMS (mean value was 3.32 × 10-3 copies/16S rRNA copies) still did not recover to the initial stage before exposure, which means that enriched ARGs in SMS were persistently remained. Moreover, non-specific immunity played an important role in resisting infection of external contamination. Besides, among antioxidant proteins, superoxide dismutase showed the highest activity. Consequently, it showed that SMS became a barrier of antibiotic resistance genes under APR exposure, and ARGs in SMS were difficult to remove once colonized. This study provided a reference for understanding the transmission, enrichment process, and ecological impact of antibiotics and ARGs in aquatic environments.

Reason and control strategy for denitrification and anammox sludge flotation in nitrogen removal process: Mechanisms, strategies and perspectives.

Anaerobic biological treatment technology, especially denitrification and anaerobic ammonia oxidation (anammox) technology as mainstream process, played dominant role in the field of biological wastewater treatment. However, the above process was prone to sludge floating during high load operation and thereby affecting the efficient and stable operation of the system. Excessive production of extracellular polymeric substance (EPS) was considered to be the main reason for anaerobic granular sludge flotation, but the summaries in this area were not comprehensive enough. In this review, the potential mechanisms of denitrification and anammox sludge floatation were discussed from the perspective of granular sludge structural characteristics, nutrient transfer, and microbial flora change respectively, and the corresponding control strategies were also summarized. Finally, this paper indicated that future research on sludge flotation should focus on reducing the negative effects of EPS in sludge particles.

Naringin attenuates Actinobacillus pleuropneumoniae-induced acute lung injury via MAPK/NF-κB and Keap1/Nrf2/HO-1 pathway.

Actinobacillus pleuropneumoniae (APP) causes porcine pleuropneumonia (PCP), which is clinically characterized by acute hemorrhagic, necrotizing pneumonia, and chronic fibrinous pneumonia. Although many measures have been taken to prevent the disease, prevention and control of the disease are becoming increasingly difficult due to the abundance of APP sera, weak vaccine cross-protection, and increasing antibiotic resistance in APP. Therefore, there is an urgent need to develop novel drugs against APP infection to prevent the spread of APP. Naringin (NAR) has been reported to have an excellent therapeutic effect on pulmonary diseases, but its therapeutic effect on lung injury caused by APP is not apparent. Our research has shown that NAR was able to alleviate APP-induced weight loss and quantity of food taken and reduce the number of WBCs and NEs in peripheral blood in mice; pathological tissue sections showed that NAR was able to prevent and control APP-induced pathological lung injury effectively; based on the establishment of an in vivo/in vitro model of APP inflammation, it was found that NAR was able to play an anti-inflammatory role through inhibiting the MAPK/NF-κB signaling pathway and exerting anti-inflammatory effects; additionally, NAR activating the Nrf2 signalling pathway, increasing the secretion of antioxidant enzymes Nqo1, CAT, and SOD1, inhibiting the secretion of oxidative damage factors NOS2 and COX2, and enhancing the antioxidant stress ability, thus playing an antioxidant role. In summary, NAR can relieve severe lung injury caused by APP by reducing excessive inflammatory response and improving antioxidant capacity.

Evaluation test and analysis of a microneedle and iontophoresis based medical device "CELLADEEP Patch" in skin improvement on ex vivo human-derived skin tissue models.

BACKGROUND: Microneedles are tiny needles, typically ranging from tens to hundreds of micrometers in length, used in various medical procedures and treatments. The tested medical device named "CELLADEEP Patch" a dissolvable microneedle therapy system (MTS), made of hyaluronic acid and collagen. And the iontophoresis technique is also applied in the system. The study aimed to evaluate the effectiveness of the "CELLADEEP Patch" in skin improvement. METHODS: Ex vivo human-derived skin tissue models were used in this study and they were divided into three different groups, namely, the Untreated Group, the Negative Control Group, and the Test Group respectively. The Untreated Group received no treatment measures, the Negative Control Group was exposed to ultraviolet B radiation (UVB) irradiation, and the Test Group was exposed to UVB irradiation and treated with "CELLADEEP Patch". Skin moisture content, transdermal water loss, and skin elasticity were evaluated by three clinical devices. Additionally, histological staining and related mRNA expression levels were also analyzed. RESULTS: The results of skin moisture content, transdermal water loss, and skin elasticity evaluation consistently illustrated that the application of "CELLADEEP Patch" led to remarkable skin improvement. And the analysis of histological staining images also confirmed the effectiveness of the "CELLADEEP Patch", especially for increasing collagen density. Moreover, the upregulation of Collagen type 1 a (COL1A1) and hyaluronan synthase 3 mRNA expression and the decrease of Matrix metalloproteinase 1 (MMP-1) and Interleukin-1 beta (IL-1ß) mRNA expression reflected its wrinkle improvement, moisturizing and anti-inflammation function. CONCLUSION: "CELLADEPP Patch", the MTS combined with the iontophoresis technique, exhibits its effectiveness in moisturizing, skin elasticity improvement, and anti-inflammatory function when applied to ex vivo human-derived skin tissue models in experiments. The study has contributed to the understanding of the "CELLADEPP Patch" and laid the foundation for subsequent animal experiments and clinical trials.

An evaluation of the effectiveness of 'ULTRACOL 200' in enhancing nasolabial fold wrinkles through cutaneous repair.

BACKGROUND: Injectable filler, a nonsurgical beauty method, has gained popularity in rejuvenating sagging skin. In this study, polydioxanone (PDO) was utilized as the main component of the ULTRACOL200 filler that helps stimulate collagenesis and provide skin radiant effects. The study aimed to evaluate and compare the effectiveness of ULTRACOL200 with other commercialized products in visually improving dermatological problems. METHODS: Herein, 31 participants aged between 20 and 59 years were enrolled in the study. 1 mL of the testing product, as well as the quantity for the compared groups was injected into each participants face side individually. Subsequently, skin texture and sunken volume of skin were measured using ANTERA 3D CS imaging technology at three periods: before the application, 4 weeks after the initial application, and 4 weeks after the 2nd application of ULTRACOL200. RESULTS: The final results of skin texture and wrinkle volume evaluation consistently demonstrated significant enhancement. Consequently, subjective questionnaires were provided to the participants to evaluate the efficacy of the testing product, illustrating satisfactory responses after the twice applications. CONCLUSION: The investigation has contributed substantially to the comprehension of a PDO-based filler (ULTRACOL200) for skin enhancement and provided profound insight for future clinical trials.

Assessing the efficacy of mesotherapy products: Ultra Exo Booster, and Ultra S Line Plus in hair growth: An ex vivo study.

In this study, scalp tissues from Korean adults between 20 and 80 without skin disease were used. Scalp tissues were processed, and hair follicles were isolated and cultured with different treatments (including Bioscalp, Ultra Exo Booster, and Ultra S Line Plus) from Ultra V company. Over 12 days, observations and measurements of hair follicle characteristics were recorded at intervals (Days 0, 3, 6, 9, and 12). The study assessed the impact of these substances on hair follicle growth and morphology. Bioscalp, combined with Ultra Exo Booster and Ultra S Line Plus, showed significant hair elongation in ex vivo. Preservation of hair bulb diameter was observed, indicating potential for sustained hair growth by exosome-based products. The hair growth cycle analysis suggested a lower transition to the catagen stage in test products from Ultra V compared to non-treated groups. The research findings indicated that the tested formulations, especially the combination of Bioscalp, Ultra Exo Booster, and Ultra S Line Plus, demonstrated significant effectiveness in promoting hair growth, maintaining the integrity of the hair bulb, and reducing the transition to the catagen stage. The study suggests promising alternative treatments for hair loss, illustrating results that were as good as those of the conventional testing product groups.

Tracking the extracellular and intracellular antibiotic resistance genes across whole year in wastewater of intensive dairy farm.

Monitoring the annual variation of antibiotic resistance genes (ARGs) in livestock wastewater is important for determining the high-risk period of transfer and spread of animal-derived antibiotic resistance into the environment. However, the knowledge regarding the variation patterns of ARGs, especially intracellular ARGs (iARGs) and extracellular ARGs (eARGs), over time in livestock wastewater is still unclear. Herein, we conducted a year-round study to trace the profiles of ARGs at a Chinese-intensive dairy farm, focusing on the shifts observed in different months. The results showed significant differences in the composition and variation between iARGs and eARGs. Tetracycline, sulfonamide, and macrolide resistance genes were the major types of iARGs, while cfr was the major type of eARG. The environmental adaptations of the host bacteria determine whether ARGs appear as intracellular or extracellular forms. The total abundance of ARGs was higher from April to September, which can be attributed to the favorable climatic conditions for bacterial colonization and increased antibiotic administration during this period. Integron was found to be highly correlated with most iARGs, potentially playing a role in the presence of these genes within cells and their similar transmission patterns in wastewater. The intracellular and extracellular bacterial communities were significantly different, primarily because of variations in bacterial adaptability to the high salt and anaerobic environment. The intracellular co-occurrence network indicated that some dominant genera in wastewater, such as Turicibacter, Clostridium IV, Cloacibacillus, Subdivision5_genera_incertae_sedis, Saccharibacteria_genera_incertae_sedis and Halomonas, were potential hosts for many ARGs. To the best of our knowledge, this study demonstrates, for the first time, the annual variation of ARGs at critical points in the reuse of dairy farm wastewater. It also offers valuable insights into the prevention and control of ARGs derived from animals.

Effects of water fluoridation on early embryonic development of zebrafish.

Fluoride has strong electronegativity and exposes diversely in nature. Water fluoridation is the most pervasive form of occurrence, representing a significant threat to human health. In this study, we investigate the morphometric and physiological alterations triggered by fluoride stimulation during the embryogenesis of zebrafish and reveal its putative effects of stage- and/or dose-dependent. Fluoride exhibits potent biological activity and can be extensively absorbed by the yolk sac, exerting significant effects on the development of multiple organs. This is primarily manifested as restricted nutrient utilization and elevated levels of lipid peroxidation, further leading to the accumulation of superoxide in the yolk sac, liver, and intestines. Moreover, pericardial edema exerts pressure on the brain and eye development, resulting in spinal curvature and reduced body length. Besides, acute fluoride exposure with varying concentrations has led to diverse teratogenic outcomes. A low dose of water fluoridation tends to induce abnormal development of the embryonic yolk sac, while vascular malformation is widely observed in all fluoride-treated groups. The effect of fluoride exposure on blood circulation is universally present, even in zebrafish larvae that do not exhibit obvious deformities. Their swimming behavior is also affected by water fluoridation, resulting in reduced activity and delayed reactions. In conclusion, this study provides valuable insights into the monitoring of environmental quality related to water fluoridation and disease prevention.

Whole exome sequencing analyses identified novel genes for Alzheimer's disease and related dementia.

INTRODUCTION: The heritability of Alzheimer's disease (AD) is estimated to be 58%-79%. However, known genes can only partially explain the heritability. METHODS: Here, we conducted gene-based exome-wide association study (ExWAS) of rare variants and single-variant ExWAS of common variants, utilizing data of 54,569 clinically diagnosed/proxy AD and related dementia (ADRD) and 295,421 controls from the UK Biobank. RESULTS: Gene-based ExWAS identified 11 genes predicting a higher ADRD risk, including five novel ones, namely FRMD8, DDX1, DNMT3L, MORC1, and TGM2, along with six previously reported ones, SORL1, GRN, PSEN1, ABCA7, GBA, and ADAM10. Single-variant ExWAS identified two ADRD-associated novel genes, SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-ß process pathways, microglia, and brain regions like hippocampus. The druggability evidence suggests that DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets. DISCUSSION: Our study contributes to the current body of evidence on the genetic etiology of ADRD. HIGHLIGHTS: Gene-based analyses of rare variants identified five novel genes for Alzheimer's disease and related dementia (ADRD), including FRMD8, DDX1, DNMT3L, MORC1, and TGM2. Single-variant analyses of common variants identified two novel genes for ADRD, including SLCO1C1 and NDNF. The identified genes were predominantly enriched in amyloid-ß process pathways, microglia, and brain regions like hippocampus. DDX1, DNMT3L, TGM2, SLCO1C1, and NDNF could be effective drug targets.