Developing Salt-Rejecting Evaporators for Solar Desalination: A Critical Review.

Solar desalination, a green, low-cost, and sustainable technology, offers a promising way to get clean water from seawater without relying on electricity and complex infrastructures. However, the main challenge faced in solar desalination is salt accumulation, either on the surface of or inside the solar evaporator, which can impair solar-to-vapor efficiency and even lead to the failure of the evaporator itself. While many ideas have been tried to address this ″salt accumulation″, scientists have not had a clear system for understanding what works best for the enhancement of salt-rejecting ability. Therein, for the first time, we classified the state-of-the-art salt-rejecting designs into isolation strategy (isolating the solar evaporator from brine), dilution strategy (diluting the concentrated brine), and crystallization strategy (regulating the crystallization site into a tiny area). Through the specific equations presented, we have identified key parameters for each strategy and highlighted the corresponding improvements in the solar desalination performance. This Review provides a semiquantitative perspective on salt-rejecting designs and critical parameters for enhancing the salt-rejecting ability of dilution-based, isolation-based, and crystallization-based solar evaporators. Ultimately, this knowledge can help us create reliable solar desalination solutions to provide clean water from even the saltiest sources.

Polypeptide N-Acetylgalactosaminyl transferase 14 is a novel mediator in pancreatic ß-cell function and growth.

Polypeptide N-Acetylgalactosaminyl transferase 14 (GALNT14) plays important roles in cancer progression and chemotherapy response. Here, we show that GALNT14 is highly expressed in pancreatic ß cells and regulates ß cell function and growth. We found that the expression level of Ganlt14 was significantly decreased in the primary islets from three rodent type-2 diabetic models. Single-Cell sequencing defined that Galnt14 was mainly expressed in ß cells of mouse islets. Galnt14 knockout (G14KO) INS-1 cell line, constructed by using CRISPR/Cas9 technology were growth normal, but showed blunt shape, and increased basal insulin secretion. Combined proteomics and glycoproteomics demonstrated that G14KO altered cell-to-cell junctions, communication, and adhesion. Insulin receptor (IR) and IGF1-1R were indirectly confirmed for GALNT14 substrates, contributed to diminished IGF1-induced p-AKT levels and cell growth in G14KO cells. Overall, this study uncovers that GALNT14 is a novel modulator in regulating ß cells biology, providing a missing link of ß cells O-glycosylation to diabetes development.

Islet-resident macrophage-derived miR-155 promotes ß cell decompensation via targeting PDX1.

Chronic inflammation is critical for the initiation and progression of type 2 diabetes mellitus via causing both insulin resistance and pancreatic ß cell dysfunction. miR-155, highly expressed in macrophages, is a master regulator of chronic inflammation. Here we show that blocking a macrophage-derived exosomal miR-155 (MDE-miR-155) mitigates the insulin resistances and glucose intolerances in high-fat-diet (HFD) feeding and type-2 diabetic db/db mice. Lentivirus-based miR-155 sponge decreases the level of miR-155 in the pancreas and improves glucose-stimulated insulin secretion (GSIS) ability of ß cells, thus leading to improvements of insulin sensitivities in the liver and adipose tissues. Mechanistically, miR-155 increases its expression in HFD and db/db islets and is released as exosomes by islet-resident macrophages under metabolic stressed conditions. MDE-miR-155 enters ß cells and causes defects in GSIS function and insulin biosynthesis via the miR-155-PDX1 axis. Our findings offer a treatment strategy for inflammation-associated diabetes via targeting miR-155.

A delayed and unsynchronized ovary development as revealed by transcriptome of brain and pituitary of Coilia nasus.

Coilia nasus is an anadromous fish that has been successfully domesticated in the last decade due to its high economic value. The fish exhibits a delayed ovary development during the reproductive season, despite breeding and selection for five to six offspring. The molecular mechanism of the delayed ovary development is still unknown, so the obstacles have not been removed in the large-scale breeding program. This study aims to investigate the key genes regulating ovarian development by comparing the transcriptomes of ovarian-stage IV and stage II brain/pituitary of Coilia nasus. Ovarian stages were validated by histological sections. A total of 75,097,641 and 66,735,592 high-quality reads were obtained from brain and pituitary transcriptomes, respectively, and alternatively spliced transcripts associated with gonadal development were detected. Compared to ovarian Ⅱ- brain, 515 differentially expressed genes (DEGs) were upregulated and 535 DEGs were downregulated in ovarian Ⅳ- brain, whereas 470 DEGs were upregulated and 483 DEGs were downregulated in ovarian Ⅳ- pituitary compared to ovarian Ⅱ- pituitary. DEGs involved in hormone synthesis and secretion and in the GnRH signaling pathway were screened. Weighted gene co-expression network analysis identified gene co-expression modules that were positively correlated with ovarian phenotypic traits. The hub genes Smad4 and TRPC4 in the modules were co-expressed with DEGs including Kiss1 receptor and JUNB, suggesting that ovarian development is controlled by a hypothalamic-pituitary-gonadal axis. Our results have provided new insights that advance our understanding of the molecular mechanism of C. nasus reproductive functions and will be useful for future breeding.

Insufficient TRPM5 Mediates Lipotoxicity-induced Pancreatic ß-cell Dysfunction.

OBJECTIVE: While the reduction of transient receptor potential channel subfamily M member 5 (TRPM5) has been reported in islet cells from type 2 diabetic (T2D) mouse models, its role in lipotoxicity-induced pancreatic ß-cell dysfunction remains unclear. This study aims to study its role. METHODS: Pancreas slices were prepared from mice subjected to a high-fat-diet (HFD) at different time points, and TRPM5 expression in the pancreatic ß cells was examined using immunofluorescence staining. Glucose-stimulated insulin secretion (GSIS) defects caused by lipotoxicity were mimicked by saturated fatty acid palmitate (Palm). Primary mouse islets and mouse insulinoma MIN6 cells were treated with Palm, and the TRPM5 expression was detected using qRT-PCR and Western blotting. Palm-induced GSIS defects were measured following siRNA-based Trpm5 knockdown. The detrimental effects of Palm on primary mouse islets were also assessed after overexpressing Trpm5 via an adenovirus-derived Trpm5 (Ad-Trpm5). RESULTS: HFD feeding decreased the mRNA levels and protein expression of TRPM5 in mouse pancreatic islets. Palm reduced TRPM5 protein expression in a time- and dose-dependent manner in MIN6 cells. Palm also inhibited TRPM5 expression in primary mouse islets. Knockdown of Trpm5 inhibited insulin secretion upon high glucose stimulation but had little effect on insulin biosynthesis. Overexpression of Trpm5 reversed Palm-induced GSIS defects and the production of functional maturation molecules unique to ß cells. CONCLUSION: Our findings suggest that lipotoxicity inhibits TRPM5 expression in pancreatic ß cells both in vivo and in vitro and, in turn, drives ß-cell dysfunction.

Association Between Serum 25-Hydroxyvitamin D and Trichomonas vaginalis Infection Among American Adults: NHANES 2013-2016.

BACKGROUND: Previous studies have suggested that vitamin D may possess anti-infection properties, but the relationship between vitamin D and Trichomonas vaginalis infection remains unexplored. METHODS: Using data from the National Health and Nutrition Examination Survey between 2013 and 2016, we conducted multivariate regression analyses and subgroup analyses to investigate the association between 25-hydroxyvitamin D (25[OH]D) levels and T. vaginalis infection, ensuring the robustness of our results. RESULTS: The final sample included data from 4318 individuals aged 20 to 59 years, among which 92 were diagnosed with T. vaginalis infection. For every 10 nmol/L increase in serum 25(OH)D level, there was a 22% reduction in the likelihood of T. vaginalis infection incidence (adjusted odds ratio [aOR], 0.78; 95% confidence interval [CI], 0.69-0.90). Similarly, higher concentration tertiles demonstrated relatively lower infection ratios compared with the tertile with the lowest 25(OH)D concentration (aOR, 0.54 [95% CI, 0.30-0.95; P = 0.030] for T2; aOR, 0.23 [95% CI, 0.09-0.61; P < 0.001] for T3). CONCLUSIONS: Our cross-sectional study indicates a negative association between 25(OH)D levels and the prevalence of T. vaginalis infection. However, further high-quality evidence is needed to establish a causal relationship between 25(OH)D levels and T. vaginalis infection, as well as to evaluate the potential role of vitamin D supplementation in preventing T. vaginalis infection.

M2 macrophages independently promote beige adipogenesis via blocking adipocyte Ets1.

Adipose tissue macrophages can promote beige adipose thermogenesis by altering local sympathetic activity. Here, we perform sympathectomy in mice and further eradicate subcutaneous adipose macrophages and discover that these macrophages have a direct beige-promoting function that is independent of sympathetic system. We further identify adipocyte Ets1 as a vital mediator in this process. The anti-inflammatory M2 macrophages suppress Ets1 expression in adipocytes, transcriptionally activate mitochondrial biogenesis, as well as suppress mitochondrial clearance, thereby increasing the mitochondrial numbers and promoting the beiging process. Male adipocyte Ets1 knock-in mice are completely cold intolerant, whereas male mice lacking Ets1 in adipocytes show enhanced energy expenditure and are resistant to metabolic disorders caused by high-fat-diet. Our findings elucidate a direct communication between M2 macrophages and adipocytes, and uncover a function for Ets1 in responding to macrophages and negatively governing mitochondrial content and beige adipocyte formation.

Two Novel and Three Recurrent Mutations in the Mevalonate Pathway Genes in Chinese Patients with Porokeratosis.

Purpose: Porokeratosis (PK) is a chronic autosomal-dominant cutaneous keratinization disorder exhibiting clinical and genetic heterogeneity. Mevalonate decarboxylase (MVD), farnesyl diphosphate synthase (FDPS), phosphomevalonate kinase(PMVK), and mevalonate kinase genes(MVK), which encode the mevalonate pathway, are disease-causing genes in PK. Patients and Methods: Data and blood samples were collected from two Chinese families and five sporadic patients with porokeratosis. Whole-exome and Sanger sequencing were performed to detect pathogenic gene mutation in the patients. Results: Five heterozygous mutations were identified, including a novel FDPS stop-gain mutation c.438T>G (p.Tyr146Ter), a novel MVD missense mutation c.683G>C (p.R228P), and three previously reported MVD mutations: c.746T>C (p.F249S), c.875A>G (p.N292S), and c.1111_1113del (p.371_371del). The novel FDPS c.438T>G mutation was predicted as "disease-causing" (p = 1) by Mutation Taster. The other novel MVD c.683G>C was also predicted as "deleterious" (score = 0.00) by Sorting Intolerant From Tolerant (SIFT), "probably damaging" (score = 1) by PolyPhen2, and "disease-causing" (p = 0.999) by Mutation Taster. Conclusion: Our results extended the mutation spectrum of mevalonate pathway genes in porokeratosis and provided useful strategies for a more accurate diagnosis and genetic counseling.

ß-Cell miRNA-503-5p Induced by Hypomethylation and Inflammation Promotes Insulin Resistance and ß-Cell Decompensation.

Chronic inflammation promotes pancreatic ß-cell decompensation to insulin resistance because of local accumulation of supraphysiologic interleukin 1ß (IL-1ß) levels. However, the underlying molecular mechanisms remain elusive. We show that miR-503-5p is exclusively upregulated in islets from humans with type 2 diabetes and diabetic rodents because of its promoter hypomethylation and increased local IL-1ß levels. ß-Cell-specific miR-503 transgenic mice display mild or severe diabetes in a time- and expression-dependent manner. By contrast, deletion of the miR-503 cluster protects mice from high-fat diet-induced insulin resistance and glucose intolerance. Mechanistically, miR-503-5p represses c-Jun N-terminal kinase-interacting protein 2 (JIP2) translation to activate mitogen-activated protein kinase signaling cascades, thus inhibiting glucose-stimulated insulin secretion (GSIS) and compensatory ß-cell proliferation. In addition, ß-cell miR-503-5p is packaged in nanovesicles to dampen insulin signaling transduction in liver and adipose tissues by targeting insulin receptors. Notably, specifically blocking the miR-503 cluster in ß-cells effectively remits aging-associated diabetes through recovery of GSIS capacity and insulin sensitivity. Our findings demonstrate that ß-cell miR-503-5p is required for the development of insulin resistance and ß-cell decompensation, providing a potential therapeutic target against diabetes. ARTICLE HIGHLIGHTS: Promoter hypomethylation during natural aging permits miR-503-5p overexpression in islets under inflammation conditions, conserving from rodents to humans. Impaired ß-cells release nanovesicular miR-503-5p to accumulate in liver and adipose tissue, leading to their insulin resistance via the miR-503-5p/insulin receptor/phosphorylated AKT axis. Accumulated miR-503-5p in ß-cells impairs glucose-stimulated insulin secretion via the JIP2-coordinated mitogen-activated protein kinase signaling cascades. Specific blockage of ß-cell miR-503-5p improves ß-cell function and glucose tolerance in aging mice.

Proteomic study of aqueous humour in diabetic patients with cataracts by TMT combined with HPLC-MS/MS.

BACKGROUND: The purpose of this study is to identify the proteomic differences between the aqueous humour of diabetes patients with cataracts and that of non-diabetic sufferers of cataracts in a clinical setting. METHODS: Patients were divided into the diabetic experimental group and the non-diabetic control group. Aqueous humour specimens were obtained via cataract surgery. Sample proteins were treated with a TMT reagent, separated using a cation chromatography column, and analysed using a C18 desalting column. Proteins were identified using HPLC-MS/MS. The differential proteins were identified using both a p value of < 0.05 and a fold change of > 1.2. GO classification enrichment analysis, KEGG pathway enrichment analysis, protein interaction network analysis, and ingenuity pathway analysis were all carried out. The expression level of four differential proteins were verified by Western blot, and GC and TTR expressions were further examined using an expanded sample pool. RESULTS: The postprandial glucose levels between the experimental group (9.40 ± 1.35 mmol/L) and the control group (6.56 ± 0.81 mmol/L) were significantly different, with a p value of 1.16E-06. It is important to note, however, that the baseline levels of the parameters showed no statistical differences. In total, 397 aqueous humour proteins were identified; of these, 137 showed significant differences, with 63 upregulated ones and 74 down-regulated ones. The differential proteins play important roles in numerous biological processes and pathways, such as complement and coagulation cascades (p = 1.71E-09). Some of these differential proteins are associated with diabetic retinal degeneration and other diabetic complications. Differential proteins, such as HP, GC, and TTR, have high node degree in the protein interaction network. Western blot results further confirmed that GC were down-regulated while TTR was up-regulated in aqueous humour under diabetic condition. CONCLUSION: A list of differential proteins in the human aqueous humour of diabetic patients was established. Proteins with high interaction scores as per protein interaction analysis, such as GC and TTR, were further verified and could potentially be used as early diagnostic markers for diabetic eye complications in clinical practice.

Phase-transited lysozyme nanofilm with co-immobilized copper ion and heparin as cardiovascular stent multifunctional coating.

Cardiovascular metal stents have shown potential in the treatment of coronary artery disease using percutaneous coronary intervention. However, thrombosis, endothelialization, and new atherosclerosis after stent implantation remain unsolved problems. Herein, a multifunctional coating material based on phase-transited lysozyme was developed to promote stent endothelialization and simultaneously reduce thrombus events by embedding moieties of heparin and co-immobilized copper ions for in-situ catalyzing nitric oxide (NO) generation. The lysozyme-based biomimetic coating is compatible with blood and enables facile loading and sustainable release of copper ions to produce NO with donors via catalytic reaction. The novel coating strategy displayed several bio-effects of anti-thrombosis; it synergistically promoted endothelial cell growth and inhibited smooth muscle cell growth. Thus, this systemic in vitro study will provide a foundation for developing multifunctional cardiovascular stents in clinical settings.

The effect of maternal vitamin D deficiency during pregnancy on glycolipid metabolism of offspring rats and the improvement of vitamin D intervention after weaning.

Background: Vitamin D deficiency during pregnancy is common, but whether maternal vitamin D status affects glycolipid metabolism of offspring remains unclear. Objective: To evaluate the effect of maternal vitamin D deficiency during pregnancy on the glycolipid metabolism of offspring at different life-cycles (from birth to adulthood) and to explore the improvement of different dosages of vitamin D supplementation. Methods: Sprague-Dawley rats were fed vitamin D-deprived (VDD group) or standard vitamin D diets (SC group) during pregnancy, and their diets were changed to standard vitamin D diets during lactation (the offspring were sorted into VDDoffspring and SCoffspring groups). After weaning, rats in the VDDoffspring group were randomly assigned to the VDDoffspring, VDDoffspring-S3300 and VDDoffspring-S10000 groups with diets containing standard, medium and high dosages of vitamin D for 12 wk. Serum was collected for biochemical analyses at postnatal Day 21, postnatal Day 56 and postnatal Day 84. Oral glucose tolerance test (OGTT) was performed at postnatal Day 70. Results: Compared to SCoffspring, rats in the VDDoffspring group had significantly lower birth weight with faster weight gain and higher levels of lipid metabolism in early life. After near adulthood, the differences in weight and lipid metabolism between the two groups disappeared. OGTT showed significantly higher blood glucose levels in the VDDoffspring group at 30 min, 60 min, and 90 min. The continuation of vitamin D supplementation at medium and high dosages after weaning did not cause any obvious changes in weight or glycolipid metabolism (except for postprandial hyperglycemia). OGTT demonstrated that the glucose levels in the VDDoffspring-S3300 group were lowest at all the time points and that those in the VDDoffspring-S10000 group were the highest at 30 min, 60 min, and 90 min among the three groups. Conclusion: The adverse effects of vitamin D deficiency during pregnancy on glycolipid metabolism in offspring vary in different stages. Over a long time period, adequate vitamin D supplementation is beneficial to glycolipid metabolism for the offspring of subjects with vitamin D deficiency during pregnancy; however, further improvement is required.

Untargeted Plasma Lipidomics Reveal Perturbed Metabolites of Glycerophospholipids, and Sphingolipids in Moderate-to-Severe Acne.

Background: Acne vulgaris (AV) is a common inflammatory disorder involving the pilosebaceous unit. The study aimed to explore the plasma lipidome signatures and identify specific lipid biomarkers in moderate-to-severe acne patients. Patients and Methods: Untargeted plasma lipidomic analysis using ultra-high performance liquid chromatography system (UHPLC) coupled to q-extraction plus was employed on 30 moderate-to-severe acne patients aged between 16-25 years and 30 healthy controls. Multivariate data analyses were used to identify the distinguishing lipid metabolites. Results: All 1449 species of 37 lipid subclasses were identified from the MS data. There were apparent differences in plasma lipid profiles between acne groups and control groups. With variable influence on projection (VIP) > 1.0 and P-value < 0.05, 26 significantly different lipid metabolites were identified. These metabolites consisted mainly of glycerophospholipids (GPs), sphingolipids (SPs), and glycerolipids (GLs). Combining with AUC≥0.800 as the elected criteria, we obtained five differential lipids with good diagnostic performance for acne severity, including 2 sphingomyelins (SM), 1 phosphatidylglycerol (PG), 1 trihexosylceramide (Hex3Cer), and 1 Phosphatidylcholine (PC). Among them, PG (44:0) had the highest AUC values. Conclusion: Our study revealed the plasma lipidome signature of patients with moderate-to-severe acne. The results will provide a novel light into the perturbed lipid metabolism leading to the development of acne.

Factors and Molecular Mechanisms of Vitamin A and Childhood Obesity Relationship: A Review.

Childhood obesity has become a public health concern. As the importance of vitamin A (VA) in the body has become increasingly acknowledged, there is limited clinical trial evidence to substantiate the association between VA and childhood obesity. Vitamin A deficiency (VAD) increases the risk of childhood obesity, a finding consistently reported in pregnant women. VA could regulate the adipogenic process, inflammation, oxidative stress and metabolism-related gene expression in mature adipocytes. VAD disrupts the balance of obesity-related metabolism, thus affecting lipid metabolism and insulin regulation. Conversely, VA supplementation has a major impact on efficacy in obesity, and obese individuals typically have a lower VA status than normal-weight individuals. Several studies have attempted to identify the genetic and molecular mechanisms underlying the association between VA and obesity. In this review, we summarize and discuss recent new developments focusing on retinol, retinoic acid, and RBP4 and elucidate and provide an overview of the complex interrelationships between these critical components of VA and childhood obesity. However, the causal relationship between VA status and childhood obesity remains unclear. It is also unknown whether VA supplementation improves the overall obesogenic metabolic profile.

A Dynamic Model of Internationalization and Innovation in Emerging Market Enterprises: Knowledge Exploration, Transformation, and Exploitation.

Drawing on organizational learning theory and taking an institutional perspective, this study investigates (1) the dynamic relationship between internationalization and innovation in emerging market enterprises (EMEs), and (2) how state ownership moderates the focal relationships. Using a panel dataset of listed Chinese firms from 2007 to 2018, we find that internationalization encourages innovation input in EMEs, which in turn transforms into more innovation output. Higher innovation output leads to further international commitment, creating a dynamic upward spiral of internationalization and innovation. Interestingly, state ownership positively moderates the innovation input-innovation output link but negatively moderates the relationship between innovation output and internationalization. Our paper enriches and refines our understanding of the dynamic relationship between internationalization and innovation in EMEs by integrating the knowledge exploration, transformation, and exploitation perspectives, with the institutional perspective of state ownership.

Two Novel and a Recurrent ATP2C1 Mutations in Chinese Population with Hailey-Hailey Disease.

Purpose: Hailey-Hailey disease (HHD), also known as familial benign chronic pemphigus, is a rare autosomal dominant inherited blistering dermatosis. Pathogenic variants in ATP2C1 have been associated with HHD since 2000. This study aimed to identify the mutations in the ATP2C1 gene in two Chinese pedigrees and two sporadic cases with HHD. Patients and Methods: Two Chinese pedigrees and two sporadic cases were included in this study. Whole-exome sequencing and Sanger sequencing were performed to detect the mutation of the ATP2C1 gene. Predictions of protein structure and function were performed using bioinformatics tools, including Mutation Taster, Polyphen-2, SIFT, and Swiss-Model. Results: In this study, we detected three heterozygous mutations, including novel compound mutations of (c.1840-4delA and c.1840_1844delGTTGC), splice site mutation of c.1570+3A>C, and a previously known nonsense mutation c.1402C>T in the ATP2C1 gene. Combined with our previous study, ten patients with c.1402C>T mutation in the ATP2C1 gene have been identified, and all these patients originated from Jiangxi Province. Conclusion: c.1402C>T mutation in the ATP2C1 gene was considered a regional highly prevalent mutation in the Chinese population with HHD. The results added new variants to the database of ATP2C1 mutations associated with HHD.

BRSK2 in pancreatic ß cells promotes hyperinsulinemia-coupled insulin resistance and its genetic variants are associated with human type 2 diabetes.

Brain-specific serine/threonine-protein kinase 2 (BRSK2) plays critical roles in insulin secretion and ß-cell biology. However, whether BRSK2 is associated with human type 2 diabetes mellitus (T2DM) has not been determined. Here, we report that BRSK2 genetic variants are closely related to worsening glucose metabolism due to hyperinsulinemia and insulin resistance in the Chinese population. BRSK2 protein levels are significantly elevated in ß cells from T2DM patients and high-fat diet (HFD)-fed mice due to enhanced protein stability. Mice with inducible ß-cell-specific Brsk2 knockout (ßKO) exhibit normal metabolism with a high potential for insulin secretion under chow-diet conditions. Moreover, ßKO mice are protected from HFD-induced hyperinsulinemia, obesity, insulin resistance, and glucose intolerance. Conversely, gain-of-function BRSK2 in mature ß cells reversibly triggers hyperglycemia due to ß-cell hypersecretion-coupled insulin resistance. Mechanistically, BRSK2 senses lipid signals and induces basal insulin secretion in a kinase-dependent manner. The enhanced basal insulin secretion drives insulin resistance and ß-cell exhaustion and thus the onset of T2DM in mice fed an HFD or with gain-of-function BRSK2 in ß cells. These findings reveal that BRSK2 links hyperinsulinemia to systematic insulin resistance via interplay between ß cells and insulin-sensitive tissues in the populations carrying human genetic variants or under nutrient-overload conditions.