Does Serum Vitamin D Level Affect COVID-19 Infection and Its Severity?-A Case-Control Study

Background: As effective medication to treat COVID-19 is currently unavailable, preventive remedies may be particularly important. Objective: To examine the relationship between serum 25-hydroxy vitamin D (25(OH)D) level and COVID-19 infection, its severity, and its clinical case characteristics. Methods: This case-control study compared serum 25(OH)D levels and rates of vitamin D deficiency (VDD) between 80 healthy controls and 62 patients diagnosed with COVID-19 and admitted to Guangxi People’s Hospital, China, 2/16/2020–3/16/2020. Cases were categorized into asymptomatic, mild/moderate, and severe/critical disease. Logistic regression analysis was conducted to examine the associations between 25(OH)D level, or VDD, and case status/severity of COVID-19 while controlling for demographics and comorbidities. A threshold level of vitamin D for conveying COVID-19 risk was estimated. Results: Severe/critical COVID-19 cases were significantly older and had higher percentages of comorbidity (renal failure) compared to mild cases. The serum 25(OH)D concentration in COVID-19 patient was much lower than that in healthy control. And 25(OH)D level was the lowest in severe/ critical cases, compared with mild cases. In further, significantly higher rates of VDD were found in COVID-19 cases (41.9%) compared to healthy controls (11.1%). And VDD was the greatest in severe/critical cases (80%), compared with mild cases (36%). These statistically significant associations remained even after controlling for demographics and comorbidities. A potential threshold of 25(OH)D (41.19nmol/L) to protect against COVID-19 was identified. Conclusion: Elderly and people with comorbidities were susceptible to severe COVID-19 infection. VDD was a risk factor for COVID-19, especially for severe/critical cases. While further confirmation is needed, vitamin D supplementation may have prevention or treatment potential for COVID- 19 disease

Sex determination and maintenance: the role of DMRT1 and FOXL2

In many species, including mammals, sex determination is genetically based. The sex chromosomes that individuals carry determine sex identity. Although the genetic base of phenotypic sex is determined at the moment of fertilization, the development of testes or ovaries in the bipotential early gonads takes place during embryogenesis. During development, sex determination depends upon very few critical genes. When one of these key genes functions inappropriately, sex reversal may happen. Consequently, an individual′s sex phenotype may not necessarily be consistent with the sex chromosomes that are present. For some time, it has been assumed that once the fetal choice is made between male and female in mammals, the gonadal sex identity of an individual remains stable. However, recent studies in mice have provided evidence that it is possible for the gonadal sex phenotype to be switched even in adulthood. These studies have shown that two key genes, doublesex and mad-3 related transcription factor 1 (Dmrt1) and forkhead box L2 (Foxl2), function in a Yin and Yang relationship to maintain the fates of testes or ovaries in adult mammals, and that mutations in either gene might have a dramatic effect on gonadal phenotype. Thus, adult gonad maintenance in addition to fetal sex determination may both be important for the fertility

Inhibitors of Testosterone Biosynthetic and Metabolic Activation Enzymes

The Leydig cells of the testis have the capacity to biosynthesize testosterone from cholesterol. Testosterone and its metabolically activated product dihydrotestosterone are critical for the development of male reproductive system and spermatogenesis. At least four steroidogenic enzymes are involved in testosterone biosynthesis: Cholesterol side chain cleavage enzyme (CYP11A1) for the conversion of cholesterol into pregnenolone within the mitochondria, 3β-hydroxysteroid dehydrogenase (HSD3B), for the conversion of pregnenolone into progesterone, 17α-hydroxylase/17,20-lyase (CYP17A1) for the conversion of progesterone into androstenedione and 17β-hydroxysteroid dehydrogenase (HSD17B3) for the formation of testosterone from androstenedione. Testosterone is also metabolically activated into more potent androgen dihydrotestosterone by two isoforms 5α-reductase 1 (SRD5A1) and 2 (SRD5A2) in Leydig cells and peripheral tissues. Many endocrine disruptors act as antiandrogens via directly inhibiting one or more enzymes for testosterone biosynthesis and metabolic activation. These chemicals include industrial materials (perfluoroalkyl compounds, phthalates, bisphenol A and benzophenone) and pesticides/biocides (methoxychlor, organotins, 1,2-dibromo-3-chloropropane and prochloraz) and plant constituents (genistein and gossypol). This paper reviews these endocrine disruptors targeting steroidogenic enzymes

One-Pot Tandem Synthesis of 2-Arylquinazolines by a Multicomponent Cyclization Reaction

A series of 2-arylquinazolines have been synthesized in moderate to excellent yields by one-pot tandem reaction of (2-aminophenyl)methanols, aldehydes and ceric ammonium nitrate (CAN). The utility of this transformation was demonstrated by its compatibility with a wide range of functional groups. Thus, the method represents a simple and practical procedure to access 2-arylquinazolines

Insights into the Development of the Adult Leydig Cell Lineage from Stem Leydig Cells

Adult Leydig cells (ALCs) are the steroidogenic cells in the testes that produce testosterone. ALCs develop postnatally from a pool of stem cells, referred to as stem Leydig cells (SLCs). SLCs are spindle-shaped cells that lack steroidogenic cell markers, including luteinizing hormone (LH) receptor and 3β-hydroxysteroid dehydrogenase. The commitment of SLCs into the progenitor Leydig cells (PLCs), the first stage in the lineage, requires growth factors, including Dessert Hedgehog (DHH) and platelet-derived growth factor-AA. PLCs are still spindle-shaped, but become steroidogenic and produce mainly androsterone. The next transition in the lineage is from PLC to the immature Leydig cell (ILC). This transition requires LH, DHH, and androgen. ILCs are ovoid cells that are competent for producing a different form of androgen, androstanediol. The final stage in the developmental lineage is ALC. The transition to ALC involves the reduced expression of 5α-reductase 1, a step that is necessary to make the cells to produce testosterone as the final product. The transitions along the Leydig cell lineage are associated with the progressive down-regulation of the proliferative activity, and the up-regulation of steroidogenic capacity, with each step requiring unique regulatory signaling

Next Decade of Telecommunications Artificial Intelligence

It has been an exciting journey since the mobile communications and artificial intelligence (AI) were conceived in 1983 and 1956. While both fields evolved independently and profoundly changed communications and computing industries, the rapid convergence of 5th generation mobile communication technology (5G) and AI is beginning to significantly transform the core communication infrastructure, network management, and vertical applications. The paper first outlined the individual roadmaps of mobile communications and AI in the early stage, with a concentration to review the era from 3rd generation mobile communication technology (3G) to 5G when AI and mobile communications started to converge. With regard to telecommunications AI, the progress of AI in the ecosystem of mobile communications was further introduced in detail, including network infrastructure, network operation and management, business operation and management, intelligent applications towards business supporting system (BSS) & operation supporting system (OSS) convergence, verticals and private networks, etc. Then the classifications of AI in telecommunication ecosystems were summarized along with its evolution paths specified by various international telecommunications standardization organizations. Towards the next decade, the prospective roadmap of telecommunications AI was forecasted. In line with 3rd generation partnership project (3GPP) and International Telecommunication Union Radiocommunication Sector (ITU-R) timeline of 5G & 6th generation mobile communication technology (6G), the network intelligence following 3GPP and open radio access network (O-RAN) routes, experience and intent-based network management and operation, network AI signaling system, intelligent middle-office based BSS, intelligent customer experience management and policy control driven by BSS & OSS convergence, evolution from service level agreement (SLA) to experience level agreement (ELA), and intelligent private network for verticals were further explored. The paper is concluded with the vision that AI will reshape the future beyond 5G (B5G)/6G landscape, and we need pivot our research and development (R&D), standardizations, and ecosystem to fully take the unprecedented opportunities

Determination of the Peak and Residual Shear Strengths of the Sandwich Material in Slopes

The mudded weak interlayer is a geotechnical sandwich material exhibiting strain softening behavior, which plays an important part in the slope stability. The present work primarily focuses on the shear strength of the mudded weak interlayer in rock slopes. To determine the peak and residual shear strengths of the mudded weak interlayers, the particle flow code (PFC) is used to simulate the failure behavior during the direct shear tests. Laboratory investigations including uniaxial compression test, SEM, and 3D deformation measurement are employed to calibrate the essential micro parameters of the mudded weak interlayer during the simulation process in PFC. The numerical model is built based on these parameters and both the peak and residual shear strengths can be predicted from the model. The prediction results show that the peak and residual internal friction angle are 19.36° and 14.61°, while the peak and residual cohesion are 22.33 kPa and 2.73 kPa, respectively. Moreover, to validate the obtained peak and residual strengths, the results are compared with literature data. The peak and residual shear strengths of the mudded weak interlayer can serve as an important benchmark to evaluate the stability of side slopes and provide guiding suggestions for their reinforcement

The Next Decade of Telecommunications Artificial Intelligence

It has been an exciting journey since the mobile communications and artificial intelligence were conceived 37 years and 64 years ago. While both fields evolved independently and profoundly changed communications and computing industries, the rapid convergence of 5G and deep learning is beginning to significantly transform the core communication infrastructure, network management and vertical applications. The paper first outlines the individual roadmaps of mobile communications and artificial intelligence in the early stage, with a concentration to review the era from 3G to 5G when AI and mobile communications started to converge. With regard to telecommunications artificial intelligence, the paper further introduces in detail the progress of artificial intelligence in the ecosystem of mobile communications. The paper then summarizes the classifications of AI in telecom ecosystems along with its evolution paths specified by various international telecommunications standardization bodies. Towards the next decade, the paper forecasts the prospective roadmap of telecommunications artificial intelligence. In line with 3GPP and ITU-R timeline of 5G & 6G, the paper further explores the network intelligence following 3GPP and ORAN routes respectively, experience and intention driven network management and operation, network AI signalling system, intelligent middle-office based BSS, intelligent customer experience management and policy control driven by BSS and OSS convergence, evolution from SLA to ELA, and intelligent private network for verticals. The paper is concluded with the vision that AI will reshape the future B5G or 6G landscape and we need pivot our R&D, standardizations, and ecosystem to fully take the unprecedented opportunities.Comment: 50 pages in English 24 figures. (Note version 5 is 19 pages, in Chinese, with 24 figures

The Inactivation of JAK2/STAT3 Signaling and Desensitization of M1 mAChR in Minimal Hepatic Encephalopathy (MHE) and the Protection of Naringin Against MHE

Background: We previously reported that elevation of intracranial dopamine (DA) levels from cirrhotic livers is implicated in the pathogenesis of minimal hepatic encephalopathy (MHE). Intracellular events in neurons, which lead to memory loss in MHE by elevated DA, however, remain elusive. Methods: In our present study, an MHE rat model, a DA - intracerebroventricularly (i.c.v.) injected rat model and DA-treated primary cortical neurons (PCNs) were used to study this issue using behavioral tests, double-labeled fluorescent staining, immunoblotting, and semi-quantitative RT-PCR. Results: Cognitive impairment was observed in MHE rats and DA (10 µg, i.c.v.)-treated rats. The levels of DA in the cerebral cortex of both MHE and DA (10 µg)-treated rats were increased. DA conversely modulated the p-JAK2/p-STAT3 levels in PCNs. In accordance, DA downregulated an anacetylcholine-producing enzyme, choline acetyltransferase (ChAT), and desensitized the M1-type muscarinic acetylcholine receptor (M1 mAChR). Furthermore, naringin completely restored cognitive function in MHE/DA (10 µg)-treated models by activating the JAK2/STAT3 axis, paralleling the upregulation of ChAT and sensitization of M1 mAChR. Conclusions: We propose a hypothesis accounting for memory impairment related to MHE: DA-dependent inactivation of the JAK2/STAT3 axis causes memory loss through cholinergic dysfunction. Our findings provide not only a novel pathological hallmark in MHE but also a novel target in MHE therapy