New phorbol ester derivatives as potent anti-HIV agents.

Tigliane esters show many biological activities, including anti-HIV-1 activity. Our aim in this study was to establish structure-anti-HIV activity relationships for four series of tigliane-type diterpenoids. We synthesized and evaluated 29 new phorbol ester derivatives for anti-HIV activity and for cytotoxicity against human tumor cell lines. Among them, three derivatives, two phorbol-13-monoesters (5d and 5e) and a phorbol-12,13-diester (6a), showed significant anti-HIV activity. We found that better anti-HIV activity was often associated with a shorter acyl ester at C-13. Particularly, compounds with a phenyl ring in the ester side chain exhibited excellent anti-HIV activity and had good safety indexes. Due to its significant anti-HIV potency with a high selectivity index, phorbol-12,13-dicinnamoate (6a) was chosen as the potential candidate for further preclinical trials.

Synthesis and in vitro anticancer activities of biotinylated derivatives of glaucocalyxin A and oridonin.

Fourteen glaucocalyxin A biotinylated derivatives, one glaucocalyxin C biotinylated derivative, and two oridonin biotinylated derivatives were designed and synthesized. Their structures were confirmed from 1H NMR, 13C NMR and HRMS data. The derivatives were evaluated for cytotoxic activities against lung (A549), cervical cancer cell line HeLa derivative (KB), multidrug-resistant KB subline (KB-VIN), triple-negative breast (MDA-MB-231), and estrogen receptor-positive breast (MCF-7) cancer cell lines.[Formula: see text].

Light/Electricity Energy Conversion and Storage for a Hierarchical Porous In2 S3 @CNT/SS Cathode towards a Flexible Li-CO2 Battery.

A photoinduced flexible Li-CO2 battery with well-designed, hierarchical porous, and free-standing In2 S3 @CNT/SS (ICS) as a bifunctional photoelectrode to accelerate both the CO2 reduction and evolution reactions (CDRR and CDER) is presented. The photoinduced Li-CO2 battery achieved a record-high discharge voltage of 3.14 V, surpassing the thermodynamic limit of 2.80 V, and an ultra-low charge voltage of 3.20 V, achieving a round trip efficiency of 98.1 %, which is the highest value ever reported (<80 %) so far. These excellent properties can be ascribed to the hierarchical porous and free-standing structure of ICS, as well as the key role of photogenerated electrons and holes during discharging and charging processes. A mechanism is proposed for pre-activating CO2 by reducing In3+ to In+ under light illumination. The mechanism of the bifunctional light-assisted process provides insight into photoinduced Li-CO2 batteries and contributes to resolving the major setbacks of the system.

The therapeutic effects of Jaceosidin on lipopolysaccharide-induced acute lung injury in mice.

Acute lung injury (ALI) results from various factors including uncontrolled pulmonary inflammation, oxidative damage and the over-activated complement with high mortality rates. Jaceosidin was a flavonoid compound with significant anti-complement activity. We aimed to investigate the therapeutic effects of Jaceosidin on ALI induced by lipopolysaccharide (LPS). Mice were orally administrated with Jaceosidin (15, 30 and 60 mg/kg) after LPS challenge. 24 h after LPS challenge, Jaceosidin could significantly decrease the lung wet-to-dry weight (W/D) ratio and the protein concentration in bronchoalveolar lavage fluid (BALF). Jaceosidin could down-regulate the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), together with up-regulation the levels of interleukin-4 (IL-4) and interleukin-10 (IL-10) in BALF. Jaceosidin could significantly decrease the levels of myeloperoxidase (MPO), cyclooxygenase-2 (COX-2) and nuclear factor-κB (NF-κB), COX-2 mRNA and NF-κB p65 mRNA together with increasing the activity of catalase (CAT). Additionally, Jaceosidin attenuated lung histopathological changes, inhibited the expressions of COX-2 and NF-κB p65 and reduced complement deposition with decreasing the levels of complement 3 (C3) and complement 3c (C3c) in serum. These data suggest that Jaceocidin may dampen the inflammatory response and decrease the levels of complement together with the antioxidant activity following LPS-induced ALI.

[Medium-chain acyl-CoA dehydrogenase deficiency: neonatal screening and follow-uP].

OBJECTIVE: To investigate the epidemiological characteristics, phenotype, genotype, and prognosis of medium-chain acyl-CoA dehydrogenase deficiency (MCADD) in the Chinese population. METHODS: A retrospective analysis was performed for the clinical data of the neonates who underwent screening with high-performance liquid chromatography-tandem mass spectrometry from January 2009 to June 2018 and were diagnosed with MCADD by gene detection. RESULTS: A total of 2 674 835 neonates underwent neonatal screening, among whom 12 were diagnosed with MCADD. Gene detection was performed for 10 neonates with MCADD and found 13 mutation types at 16 mutation sites of the ACADM gene, among which there were 7 reported mutations (p.T150Rfs*4, p.M1V, p.R206C, p.R294T, p.G310R, p.M328V, and p.G362E), 5 novel mutations (p.N194D, p.A324P, p.N366S, c.118+3A>G, and c.387+1del G), and 1 exon 11 deletion; p.T150Rfs*4 was the most common mutation (4/16). The detection rate of mutation sites in the ACADM gene was 80%. No phenotype-genotype correlation was observed. Dietary guidance and symptomatic treatment were given after confirmed diagnosis. No acute metabolic imbalance was observed within 4-82 months of follow-up. All neonates had good prognosis except one who had brain dysplasia. CONCLUSIONS: MCADD is relatively rare in southern China, and p.T150Rfs*4 is a common mutation in the Chinese population. Cases with positive screening results should be evaluated by octanoylcarnitine C8 value and gene detection.

The association of HLA-B27 and Klebsiella pneumoniae in ankylosing spondylitis: A systematic review.

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis of unknown origin. Its autoimmune origin has been suggested but never proven. Several reports have implicated K. pneumoniae as a triggering or perpetuating factor in AS; and the HLA-B27 antigen has also been found in association with AS. But there is no satisfactory explanation of why the presence of HLA-B27 predisposes to AS and the precise role played by K. pneumoniae in the disease has not yet been clarified. However, various studies have shown that the results of molecular, immunological, and microbiological studies could establish the link between K. pneumoniae infections and HLA-B27 in the aetiopathogenesis of AS. In this review, we have examined the evidence linking the interaction between K. pneumoniae infections and HLA-B27 in AS, and tried to exploit the possible mechanisms by which K. pneumoniae infections might induce pathologic processes to develop novel diagnostic criteria. Finally, we have also summarized some dietary regimens that could be helpful in the therapeutic management of AS patients.

Association between VDR polymorphisms and multiple sclerosis: systematic review and updated meta-analysis of case-control studies.

Vitamin D receptor (VDR) polymorphisms have been inconsistently investigated in multiple sclerosis (MS). However, published studies demonstrated differences concerning design and effect size. A meta-analysis is necessary to determine the magnitude of the association between VDR polymorphisms and MS risk. The aim of the current study was to quantify the magnitude of the association between BsmI, FokI, ApaI, and TaqI VDR polymorphisms and MS risk. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic search and meta-analysis of the VDR gene polymorphisms and the risk of MS. The pooled odds ratios (OR) and 95% confidence interval (CI) were calculated by using Stata Version 11.0 with dominant and recessive models and allele analyses. A total of 4013 cases and 4218 controls in 24 case-control studies were included in the meta-analyses. The results did not indicate an association between any of the VDR polymorphisms and the risk of MS among overall populations, Asians, and Caucasians. However, our subgroup analysis suggests that the A allele was associated with MS risk in Asian populations (P = 0.005, OR = 1.267, 95% CI 1.074-1.496). Interestingly, the sensitivity analysis excluding studies with controls not in HWE showed insignificant association between the A allele and MS risk (P = 0.211), which was different from those in the non-sensitivity analysis. Our preliminary results indicate the VDR gene ApaI, BsmI, FokI, and TaqI polymorphisms may not be associated with elevated MS risk among overall populations. But ApaI polymorphism may confer different susceptibility to MS among different populations, and more well-designed studies with a large sample size are still needed to validate our results.

The association between homocysteine and systemic sclerosis: A review of the literature and meta-analysis.

OBJECTIVES: The main objective of this study was to summarize the existing evidence and quantitatively evaluate whether serum/plasma levels of homocysteine (Hcy) were associated with sclerosis (SSc) diseases by performing a meta-analysis of previous studies. METHODS: PubMed, Elsevier ScienceDirect and Cochrane Library databases were used to obtain all relative published literatures. Stata version 11.0 (StataCorp, College Station, TX) was used for statistical analysis. The effect size of each study was calculated by the standardized mean difference (SMD) with 95% confidence interval (CI) or quartiles. RESULTS: A total of eight studies including 475 cases and 265 controls were finally included in this meta-analysis. We found significant between-study heterogeneity and conducted analyses using random-effects models. No significant association was found between the serum levels of Hcy and SSc (pooled SMD =1.382 µmol/L, 95%CI = -0.442 to 3.206, p = .137), but there are two outlier studies that deviate significantly from most other studies, which made it difficult to generalize these results. After excluding these two studies, six studies were included in the meta-analysis. The results showed that the serum levels of Hcy in SSc were significantly higher than that in healthy controls (pooled SMD = 1.182µmol/L, 95%CI = 0.230-2.134, p = .015). CONCLUSION: Serum/plasma levels of Hcy in SSc diseases were higher than that in healthy controls.

Association between cigarette smoking and impaired clinical symptoms in systemic sclerosis: A review.

It has been established that smoking has a profound impact on susceptibility and severity in some rheumatic diseases (e.g., rheumatoid arthritis), a mild impact in others (e.g., systemic lupus erythematosus) through epidemiological studies. And smoking is known to affect many inflammatory and autoimmune diseases through various mechanisms, including immunomodulation and chemical exposure. Although similar studies investigating the role of cigarette exposure in susceptibility to SSc have been rarely reported and specific mechanisms have never been established, the relationship between smoking and some SSc-related symptoms have been demonstrated during the last decade. However, due to the diversity of study designs, control populations, patient populations and the methodology used to determine smoking history, these results are contradictory in some respects. This paper will review current evidence on the association between smoking and SSc and summarize potential mechanisms.

Serum adipokines levels in patients with systemic sclerosis: A meta-analysis.

BACKGROUND: Systemic sclerosis is an chronic inflammatory autoimmune diseases. Adipokine has been reported to play an important role in modulating immune responses. Recent studies suggest that adipokine also plays some roles in the pathogenesis of systemic sclerosis (SSc). However, published data regarding the relationship between plasma/serum adipokine levels and SSc are contradictory. The aim of this study was at performing a meta-analysis to derive a more accurate estimation and further investigate the association of plasma/serum leptin and adiponectin levels with SSc patients. METHODS: PubMed, and Web of Science databases (up to Feb 20, 2016) were used to obtain all relative published literatures. The study quality was assessed by the Newcastle-Ottawa scale. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by random-effect model analysis. RESULTS: A total of fourteen studies were finally included in this meta-analysis. Among them, six of which were studied for the serum adiponectin levels in SSc patients, six of which were studied for the serum leptin levels in SSc patients, and two of them were studied both for serum adiponectin levels and serum leptin levels in SSc patients. The meta-analysis results showed that the serum adiponectin levels in SSc patients were significantly lower than that in normal controls (SMD = -0.608 ng/ml, 95% CI = -1.029 to -0.186, p = 0.005). However, there were no significant differences in serum leptin levels between SSc patients and healthy controls (SMD = -0.990 ng/ml, 95% CI = -2.340 to 0.359, p = 0.150). The subgroup analysis showed that Asia SSc patients with age less than 50 years old had lower plasma/serum adiponectin levels when compared with controls. CONCLUSION: The serum adiponectin levels, but not serum leptin levels, in SSc patients were significantly lower than that in normal controls.

E3 ubiquitin ligase: A potential regulator in fibrosis and systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis in the skin and internal organs. The pathogenesis of SSc is not completely understood until now. Recently, many studies have focused on the role of E3 ubiquitin ligases in organ fibrosis. However, the possible regulatory mechanisms of E3 ubiquitin ligases in fibrosis and SSc are not well documented. In this review, we summarized that E3 ubiquitin ligases regulated fibrosis through ubiquitin-mediated degradation of TGF-ß/Smad signaling pathway. Moreover, E3 ubiquitin ligases participated in regulating fibrosis by other methods, such as inducing epithelial transition to mesenchymal cell, enhancing the production of TGF-ß and protecting activated hepatic stellate cells from apoptosis. However, the specific regulatory mechanisms of E3 ubiquitin ligases in scleroderma is still not fully understood. There are more works to be done to specify the mechanism of E3 ubiquitin ligases in regulation of fibrosis in SSc.

Impact of meteorological changes on the incidence of scarlet fever in Hefei City, China.

Studies on scarlet fever with meteorological factors included were few. We aimed to illustrate meteorological factors' effects on monthly incidence of scarlet fever. Cases of scarlet fever were collected from the report of legal infectious disease in Hefei City from 1985 to 2006; the meteorological data were obtained from the weather bureau of Hefei City. Monthly incidence and corresponding meteorological data in these 22 years were used to develop the model. The model of auto regressive integrated moving average with covariates was used in statistical analyses. There was a highest peak from March to June and a small peak from November to January. The incidence of scarlet fever ranges from 0 to 0.71502 (per 105 population). SARIMAX (1,0,0)(1,0,0)12 model was fitted with monthly incidence and meteorological data optimally. It was shown that relative humidity (ß = -0.002, p = 0.020), mean temperature (ß = 0.006, p = 0.004), and 1 month lag minimum temperature (ß = -0.007, p < 0.001) had effect on the incidence of scarlet fever in Hefei. Besides, the incidence in a previous month (AR(ß) = 0.469, p < 0.001) and in 12 months before (SAR(ß) = 0.255, p < 0.001) was positively associated with the incidence. This study shows that scarlet fever incidence was negatively associated with monthly minimum temperature and relative humidity while was positively associated with mean temperature in Hefei City, China. Besides, the ARIMA model could be useful not only for prediction but also for the analysis of multiple correlations.

The Influence of Different Solvents on Systemic Sclerosis: An Updated Meta-analysis of 14 Case-Control Studies.

BACKGROUND: Several studies have collected detailed data to examine which specific solvents account for the association between solvents and risk of systemic sclerosis (SSc). These studies generally reported elevated risks associated with many of the specific solvents examined, such as toluene, xylene, and trichloroethylene. The previous meta-analysis was not able to conduct separate analyses for specific solvent subtypes. OBJECTIVE: The aims of the new meta-analysis were to investigate a more comprehensive estimate and to consider the effect of different solvents on SSc. METHODS: We searched PubMed, Biosis Previews, China National Knowledge Infrastructure, and Wanfang for all articles published before July 2015. Fourteen case-control studies (1657 patients and 3838 controls) were included. The quality of studies was scored according to the Newcastle-Ottawa scale. The final odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a fixed- or random-effects model according to heterogeneity test. Publication bias was assessed using Begg test. RESULTS: The risk of SSc was significantly different among sex, age, and exposure assessment methods. Separate analyses for specific solvent subtypes indicated that SSc was associated with aromatic solvents (OR, 2.72; 95% CI, 1.21-6.09), trichloroethylene (OR, 2.07; 95% CI, 1.34-3.17), halogenated solvents (OR, 1.49; 95% CI, 1.12-1.99), and ketones (OR, 4.20; 95% CI, 2.19-8.06). CONCLUSIONS: Exposure to identified types solvents does seem to be a risk factor for developing SSc. Needed efforts to decrease such exposures are discussed.

Role of anti-inflammatory cytokines IL-4 and IL-13 in systemic sclerosis.

OBJECTIVE: The aim of this paper is to review the anti-inflammatory cytokines IL-4 and IL-13 and their receptor signals; we discuss new insight into their possible roles in systemic sclerosis (SSc) and their overlapping function in SSc. INTRODUCTION: SSc is a connective tissue disease characterized by fibrosis. The exact etiology of SSc is unknown, and no therapy has been proved effective in modifying its course. Recently the roles of IL-4 and IL-13 in the development of SSc have been extensively considered. The possible roles of IL-4 and IL-13, especially their overlapping function, in SSc are not well documented. METHODS: A literature survey was performed using a PubMed database search to gather complete information regarding IL-4 and IL-13 and their role in inflammation. RESULTS AND CONCLUSIONS: The participation of complex pathways of IL-4 and IL-13 in the process of inflammation and fibrosis action in SSc is still not very clear, and some pathogenesis of regulation found in vitro needs to be further proved. There is still more work which could be done to achieve useful developments with therapeutic benefit in SSc.

The epidemiology of alcohol consumption and multiple sclerosis: a review.

Alcohol consumption is accounted for a large proportion in patients with multiple sclerosis (MS) and may be a modifiable lifestyle factor that affects the risk of developing the disease. The epidemiological studies about the association between MS and alcohol consumption have got corresponding studies during the last decade. It has been suggested that alcohol consumption was associated with mood disorders, disability and even onset of MS, but a common theme is lacking. To make an understanding of the effect of alcohol consumption on MS, the related epidemiological evidence and potential mechanisms are reviewed.

Comprehensive newborn screening for severe combined immunodeficiency, X-linked agammaglobulinemia, and spinal muscular atrophy: the Chinese experience.

BACKGROUND: Newborn screening (NBS) for severe combined immunodeficiency (SCID), X-linked agammaglobulinemia (XLA), and spinal muscular atrophy (SMA) enables early diagnosis and intervention, significantly improving patient outcomes. Advances in real-time polymerase chain reaction (PCR) technology have been instrumental in facilitating their inclusion in NBS programs. METHODS: We employed multiplex real-time PCR to simultaneously detect T-cell receptor excision circles (TRECs), kappa-deleting recombination excision circles (KRECs), and the absence of the survival motor neuron (SMN) 1 gene in dried blood spots from 103,240 newborns in Zhejiang Province, China, between July 2021 and December 2022. RESULTS: Of all the samples, 122 were requested further evaluation. After flow cytometry evaluation and/or genetic diagnostics, we identified one patient with SCID, two patients with XLA, nine patients with SMA [one of whom also had Wiskott-Aldrich Syndrome (WAS)], and eight patients with other medical conditions. The positive predictive values (PPVs) of NBS for SCID, XLA, and SMA were 2.44%, 2.78%, and 100%, respectively. The estimated prevalence rates in the Chinese population were 1 in 103,240 for SCID, 1 in 51,620 for XLA, and 1 in 11,471 for SMA. CONCLUSION: This study represents the first large-scale screening in mainland China using a TREC/KREC/SMN1 multiplex assay, providing valuable epidemiological data. Our findings suggest that this multiplex assay is an effective screening method for SCID, XLA, and SMA, potentially supporting the universal implementation of NBS programs across China.

Use of parsimony analysis to identify areas of endemism of chinese birds: implications for conservation and biogeography.

Parsimony analysis of endemicity (PAE) was used to identify areas of endemism (AOEs) for Chinese birds at the subregional level. Four AOEs were identified based on a distribution database of 105 endemic species and using 18 avifaunal subregions as the operating geographical units (OGUs). The four AOEs are the Qinghai-Zangnan Subregion, the Southwest Mountainous Subregion, the Hainan Subregion and the Taiwan Subregion. Cladistic analysis of subregions generally supports the division of China's avifauna into Palaearctic and Oriental realms. Two PAE area trees were produced from two different distribution datasets (year 1976 and 2007). The 1976 topology has four distinct subregional branches; however, the 2007 topology has three distinct branches. Moreover, three Palaearctic subregions in the 1976 tree clustered together with the Oriental subregions in the 2007 tree. Such topological differences may reflect changes in the distribution of bird species through circa three decades.

The association between reproductive factors and systemic sclerosis in Chinese women: A case-control study and meta-analysis.

AIM: To examine the associations between female menstrual or reproductive factors and the development of systemic sclerosis (SSc) in China. METHODS: In this hospital-based case-control study, for each subject, data on reproductive and menstrual factors such as number of births, abortions, and age at menarche were obtained by structured questionnaire. Risk estimates, measured by the odds ratio (OR) and 95% confidence interval (CI), were obtained by unconditional logistics regression. Furthermore, meta-analysis was performed and pooled OR with 95% CI for the number of pregnancies and abortions were calculated. RESULTS: There were 166 SSc and 392 female controls seen during the study period. The results showed women with late menarche age (≥17 years) were less likely than those with earlier age at menarche to develop SSc (OR 0.347, 95% CI 0.174-0.693) and compared with women without abortion, women with abortion (1 time) were at reduced risk of developing SSc (P = .036). After adjusting for potential confounders such as occupation and body mass index (BMI), late age at menarche (≥17 years) was associated with a decreased risk of SSc (OR 0.187, 95% CI 0.068-0.513), but abortions were not significantly related to SSc. The meta-analysis revealed there was no association between SSc and abortions or number of pregnancies. No significant publication bias was observed (P > .05). CONCLUSION: Late age at menarche was associated with a reduced risk of SSc but abortion may not be an independent risk factor for SSc. Further investigations are required to verify our findings.

Effects of meteorological factors on incidence of scarlet fever during different periods in different districts of China.

OBJECTIVE: To reveal the difference of meteorological effect on scarlet fever in Beijing and Hong Kong, China, during different periods among 2004-2014. METHODS: The data of monthly incidence of scarlet fever and meteorological variables from 2004 to 2014 in Beijing and Hong Kong were collected from Chinese science data center of public health, meteorological data website and Hong Kong observatory website. The whole study period was separated into two periods by the outbreak year 2011 (Jan 2004-Dec 2010 and Jan 2011-Dec 2014). A generalized additive Poisson model was conducted to estimate the effect of meteorological variables on monthly incidence of scarlet fever during two periods in Beijing and Hong Kong, China. RESULTS: Incidence of scarlet fever in two districts were compared and found the average incidence during period of 2004-2010 were significantly different (Z=203.973, P<0.001) while average incidence became generally equal during 2011-2014 (Z=2.125, P>0.05). There was also significant difference in meteorological variables between Beijing and Hong Kong during whole study period, except air pressure (Z=0.165, P=0.869). After fitting GAM model, it could be found monthly mean temperature showed a negative effect (RR=0.962, 95%CI: 0.933, 0.992) on scarlet fever in Hong Kong during the period of 2004-2010. By comparison, for data in Beijing during the period of 2011-2014, the RRs of monthly mean temperature range growing 1°C and monthly sunshine duration growing 1h was equal to 1.196(1.022, 1.399) and 1.006(1.001, 1.012), respectively. The changes of meteorological effect on scarlet fever over time were not significant both in Beijing and Hong Kong. CONCLUSION: This study suggests that meteorological variables were important factors for incidence of scarlet fever during different period in Beijing and Hong Kong. It also support that some meteorological effects were opposite in different period although these differences might not completely statistically significant.

Association between the serum level of vitamin D and systemic sclerosis in a Chinese population: a case control study.

AIM: Several autoimmune diseases have been associated with reduced vitamin D levels. However, the serum level of vitamin D in Chinese systemic sclerosis (SSc) patients have not been reported. The aim of this study was to evaluate the serum levels of vitamin D in Chinese SSc patients and analyze the association between vitamin D and SSc. METHODS: 25-hydroxy vitamin D 125 I RIA kit was applied to evaluate the serum levels of vitamin D in 60 SSc patients and 60 healthy controls from Anhui Provincial Hospital, China. The data of epidemiological and clinical characteristics of SSc patients were also collected. RESULTS: The serum levels of vitamin D were significantly lower in SSc patients than that in healthy controls (26.51 ± 6.27 vs. 36.29 ± 14.24 ng/mL, P < 0.001). The ratio of pulmonary involvement in vitamin D insufficiency patients was higher than that in normal vitamin D patients, but the difference missed statistical significance. The differences in other aspects were not statistically significant in the two groups. CONCLUSION: Serum levels of vitamin D in patients with SSc were lower than that in healthy controls. Further studies are needed to determine whether vitamin D supplement could provide some positive effects.