Visible-Light-Promoted Thiolation of Benzyl Chlorides with Thiosulfonates via a Photoactive Electron Donor-Acceptor Complex.

Visible-light-promoted thiolation of benzyl chlorides with thiosulfonates is disclosed via an electron donor-acceptor complex strategy. In addition to efficiently delivering a series of arylbenzylsulfide compounds, versatile thioglycosides were also successfully constructed by applying the metal- and photocatalyst-free protocol. Preliminary mechanistic studies suggest that a radical-radical coupling process was involved in this transformation.

FCMSTrans: Accurate Prediction of Disease-Associated nsSNPs by Utilizing Multiscale Convolution and Deep Feature Combination within a Transformer Framework.

Nonsynonymous single-nucleotide polymorphisms (nsSNPs), implicated in over 6000 diseases, necessitate accurate prediction for expedited drug discovery and improved disease diagnosis. In this study, we propose FCMSTrans, a novel nsSNP predictor that innovatively combines the transformer framework and multiscale modules for comprehensive feature extraction. The distinctive attribute of FCMSTrans resides in a deep feature combination strategy. This strategy amalgamates evolutionary-scale modeling (ESM) and ProtTrans (PT) features, providing an understanding of protein biochemical properties, and position-specific scoring matrix, secondary structure, predicted relative solvent accessibility, and predicted disorder (PSPP) features, which are derived from four protein sequences and structure-oriented characteristics. This feature combination offers a comprehensive view of the molecular dynamics involving nsSNPs. Our model employs the transformer's self-attention mechanisms across multiple layers, extracting higher-level and abstract representations. Simultaneously, varied-level features are captured by multiscale convolutions, enriching feature abstraction at multiple echelons. Our comparative analyses with existing methodologies highlight significant improvements made possible by the integrated feature fusion approach adopted in FCMSTrans. This is further substantiated by performance assessments based on diverse data sets, such as PredictSNP, MMP, and PMD, with areas under the curve (AUCs) of 0.869, 0.819, and 0.693, respectively. Furthermore, FCMSTrans shows robustness and superiority by outperforming the current best predictor, PROVEAN, in a blind test conducted on a third-party data set, achieving an impressive AUC score of 0.7838. The Python code of FCMSTrans is available at https://github.com/gc212/FCMSTrans for academic usage.

Strategies to inTerrupt RAbies Transmission for the Elimination Goal by 2030 In China (STRATEGIC): a modelling study.

BACKGROUND: A global plan has been set to end human deaths from dog-mediated rabies by 2030 ("Zero-by-30"), but whether it could be achieved in some countries, such as China, remains unclear. Although elimination strategies through post-exposure prophylaxis (PEP) use, dog vaccination, and patient risk assessments with integrated bite case management (IBCM) were proposed to be cost-effective, evidence is still lacking in China. We aim to evaluate the future burdens of dog-mediated human rabies deaths in the next decade and provide quantitative evidence on the cost-effectiveness of different rabies-control strategies in China. METHODS: Based on data from China's national human rabies surveillance system, we used decision-analytic modelling to estimate dog-mediated human rabies death trends in China till 2035. We simulated and compared the expected consequences and costs of different combination strategies of the status quo, improved access to PEP, mass dog vaccination, and use of IBCM. RESULTS: The predicted human rabies deaths in 2030 in China will be 308 (95%UI: 214-411) and remain stable in the next decade under the status quo. The strategy of improved PEP access alone could only decrease deaths to 212 (95%UI: 147-284) in 2028, remaining unchanged till 2035. In contrast, scaling up dog vaccination to coverage of 70% could eliminate rabies deaths by 2033 and prevent approximately 3,265 (95%UI: 2,477-3,687) extra deaths compared to the status quo during 2024-2035. Moreover, with the addition of IBCM, the "One Health" approach through mass dog vaccination could avoid unnecessary PEP use and substantially reduce total cost from 12.53 (95%UI: 11.71-13.34) to 8.73 (95%UI: 8.09-9.85) billion US dollars. Even if increasing the total costs of IBCM from 100 thousand to 652.10 million US dollars during 2024-2035, the combined strategy of mass dog vaccination and use of IBCM will still dominate, suggesting the robustness of our results. CONCLUSIONS: The combined strategy of mass dog vaccination and IBCM requires collaboration between health and livestock/veterinary sectors, and it could eliminate Chinese rabies deaths as early as 2033, with more deaths averted and less cost, indicating that adding IBCM could reduce unnecessary use of PEP and make the "One Health" rabies-control strategy most cost-effective.

Corrected MRI Pulmonary Transit Time for Identification of Combined Precapillary and Postcapillary Pulmonary Hypertension in Patients With Left Heart Disease.

BACKGROUND: The identification of combined precapillary and postcapillary pulmonary hypertension (CpcPH) in patients with pulmonary hypertension (PH) due to left heart disease (LHD) can influence therapy and outcome and is currently based on invasively determined hemodynamic parameters. PURPOSE: To investigate the diagnostic value of MRI-derived corrected pulmonary transit time (PTTc) in PH-LHD sub-grouped according to hemodynamic phenotypes. STUDY TYPE: Prospective observational study. POPULATION: A total of 60 patients with PH-LHD (18 with isolated postcapillary PH [IpcPH] and 42 with CpcPH), and 33 healthy subjects. FIELD STRENGTH/SEQUENCE: A 3.0 T/balanced steady-state free precession cine and gradient echo-train echo planar pulse first-pass perfusion. ASSESSMENT: In patients, right heart catheterization (RHC) and MRI were performed within 30 days. Pulmonary vascular resistance (PVR) was used as the diagnostic "reference standard." The PTTc was calculated as the time interval between the peaks of the biventricular signal-intensity/time curve and corrected for heart rate. PTTc was compared between patient groups and healthy subjects and its relationship to PVR assessed. The diagnostic accuracy of PTTc for distinguishing IpcPH and CpcPH was determined. STATISTICAL TESTS: Student's t-test, Mann-Whitney U-test, linear and logistic regression analysis, and receiver-operating characteristic curves. Significance level: P < 0.05. RESULTS: PTTc was significantly prolonged in CpcPH compared with IpcPH and normal controls (17.28 ± 7.67 vs. 8.82 ± 2.55 vs. 6.86 ± 2.11 seconds), and in IpcPH compared with normal controls (8.82 ± 2.55 vs. 6.86 ± 2.11 seconds). Prolonged PTTc was significantly associated with increased PVR. Furthermore, PTTc was a significantly independent predictor of CpcPH (odds ratio: 1.395, 95% confidence interval: 1.071-1.816). The area under curve was 0.852 at a cut-off value of 11.61 seconds for PTTc to distinguish between CpcPH and IpcPH (sensitivity 71.43% and specificity 94.12%). DATA CONCLUSION: PTTc may be used to identify CpcPH. Our findings have potential to improve selection for invasive RHC for PH-LHD patients. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Intrathecal Injection of Botulinum Toxin Type A has an Analgesic Effect in Male Rats CCI Model by Inhibiting the Activation of Spinal P2X4R.

Purinergic receptor P2X4 (P2X4R) plays an essential role in neuropathic pain. However, the specific mechanism needs to be clarified. Botulinum toxin type A is a neurotoxin produced by Clostridium botulinum type A. This study found that intrathecal injection of botulinum toxin type A produced an excellent analgesic effect in a rat model of chronic constriction sciatic nerve injury and inhibited the activation of P2X4R, microglia, and astrocytes. The administration of a P2X4R activator can up-regulate the expression of P2X4R and eliminate the analgesic effect of intrathecal injection of botulinum toxin type A. In addition, we found that microglia and astrocytes in the spinal cord of rats injected with botulinum toxin type A were reactivated after administration of the P2X4R activator. Our results suggest that intrathecal injection of botulinum toxin type A has an analgesic effect in a rat model of chronic constriction sciatic nerve injury by inhibiting the activation of P2X4R in the spinal cord.

A mixed-reality stimulator for lumbar puncture training: a pilot study.

BACKGROUND: The simulation is one of the basic methods of medical education, which is often used for procedural skills training. However, the existing simulator lacks internal anatomical landmarks. The study developed a mixed-reality stimulator and evaluated its usability and feasibility in lumbar puncture training. METHODS: The study recruited 40 subjects, including medical students, residents and faulty with varied levels of experience. Before training, participants completed the questionnaire about the basic information and watched a presentation about mixed reality. After practicing on mixed-reality stimulator, which provided internal anatomical structure, the examination was carried out and the results were documented. At the end of the training, trainees completed a survey of MR technology. RESULTS: In this study, participants generally believed that the MR technology was very realistic (90%), and that the presentation of internal anatomy could help the operation (95%). Moreover, 72.5% and 75%, respectively, strongly agreed that the MR technology promoted learning and should be used in medical training. After this training, the success rate of puncture and the puncture time were significantly improved in experienced and non-experienced participants. CONCLUSION: The existing simulator was easy to be transformed into MR simulator. This study showed the usability and feasibility of MR simulator in lumbar puncture training. As a potentially good tool to simulated medical skills training, next, MR technology would be developed and evaluated in more clinical skills teaching scenarios.

Diverse Right Ventricular Remodeling Evaluated by MRI and Prognosis in Eisenmenger Syndrome With Different Shunt Locations.

BACKGROUND: Congenital shunt location is related to Eisenmenger syndrome (ES) survival. Moreover, right ventricular (RV) remodeling is associated with poor survival in pulmonary hypertension. PURPOSE: To investigate RV remodeling using comprehensive magnetic resonance imaging (MRI) techniques and identify its relationship with prognosis in ES subgroups classified by shunt location. STUDY TYPE: Prospective observational study. POPULATION: Fifty-four adults with ES (16 with pre-tricuspid shunt and 38 with post-tricuspid shunt). FIELD STRENGTH/SEQUENCE: 3.0 T/cine MRI with balanced steady-state free precession sequence, late gadolinium enhancement with inversion recovery segmented gradient echo sequence and phase-sensitive reconstruction, and T1 mapping with modified Look-Locker inversion recovery sequence. ASSESSMENT: Demographics, clinical characteristics, hemodynamics, RV remodeling features (morphology, systolic function, RV-pulmonary artery (PA) coupling and myocardial fibrosis), and prognosis were compared between ES subgroups. The adverse endpoint was all-cause mortality or readmission for heart failure. STATISTICAL TESTS: The independent samples t-test, Fisher's exact test or Chi-squared test, and the Kaplan-Meier method were used. P < 0.05 was considered significant. RESULTS: Compared to patients with post-tricuspid shunt, patients with pre-tricuspid shunt were significantly older and had higher N-terminal pro-B-type natriuretic peptide concentrations and poorer exercise tolerance. Pre-tricuspid shunt showed significantly larger RV dimensions (end-diastolic volume index: 185.81 ± 37.49 vs. 98.20 ± 36.26 mL/m2 ), worse RV ejection fraction (23.54% ± 12.35% vs. 40.82% ± 10.77%), and RV-PA decoupling (0.35 ± 0.31 vs. 0.72 ± 0.29). Biventricular myocardial fibrosis was significantly more severe in pre-tricuspid shunt than post-tricuspid shunt (extracellular volume, left ventricle: 35.85% ± 2.58% vs. 29.10% ± 5.20%; RV free wall: 30.93% ± 5.65% vs. 26.75% ± 5.15%). In addition, pre-tricuspid shunt demonstrated a significantly increased risk of adverse endpoint (hazard ratio: 2.938, 95% confidence interval: 1.204-7.172). DATA CONCLUSION: ES with pre-tricuspid shunt might be a unique subtype with worse clinically decompensated RV remodeling and poor prognosis. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 5.

First-pass perfusion cardiovascular magnetic resonance parameters as surrogate markers for left ventricular diastolic dysfunction: a validation against cardiac catheterization.

OBJECTIVES: The non-invasive assessment of left ventricular (LV) diastolic dysfunction remains a challenge. The role of first-pass perfusion cardiac magnetic resonance (CMR) parameters in quantitative hemodynamic analyses has been reported. We therefore aimed to validate the diagnostic ability and accuracy of such parameters against cardiac catheterization for LV diastolic dysfunction in patients with left heart disease (LHD). METHODS: We retrospectively enrolled 77 LHD patients who underwent CMR imaging and cardiac catheterization. LV diastolic dysfunction was defined as pulmonary capillary wedge pressure (PCWP) or LV end-diastolic pressure (LVEDP) > 12 mmHg on catheterization. On first-pass perfusion CMR imaging, pulmonary transit time (PTT) was measured as the time for blood to pass from the left ventricle to the right ventricle (RV) through the pulmonary vasculature. Pulmonary transit beat (PTB) was the number of cardiac cycles within the interval, and pulmonary blood volume indexed to body surface area (PBVi) was the product of PTB and RV stroke volume index (RVSVi). RESULTS: Of the 77 LHD patients, 53 (68.83%) were found to have LV diastolic dysfunction, and showed significantly higher PTTc, PTB, and PBVi (p < 0.05) compared with those without. In multivariate analyses, only PTTc and PTB were identified as independent predictors of LV diastolic dysfunction (p < 0.05). With an optimal cutoff of 11.9 s, PTTc yielded the best diagnostic performance for LV diastolic dysfunction (area under the curve = 0.83, p < 0.001). CONCLUSIONS: PTTc may represent a non-invasive quantitative surrogate marker for the detection and assessment of diastolic dysfunction in LHD patients. KEY POINTS: • PTTc yielded the best diagnostic accuracy for diastolic dysfunction, with an optimal cutoff of 11.9 s, and a specificity of 100%. • PTTc and PTB were found to be independent predictors of LV diastolic dysfunction across different multivariate models with high reproducibility. • PTTc is a promising non-invasive surrogate marker for the detection and assessment of diastolic dysfunction in LHD patients.

Detection and evaluation of myocardial fibrosis in Eisenmenger syndrome using cardiovascular magnetic resonance late gadolinium enhancement and T1 mapping.

BACKGROUND: Myocardial fibrosis is a common pathophysiological process involved in many cardiovascular diseases. However, limited prior studies suggested no association between focal myocardial fibrosis detected by cardiovascular magnetic resonance (CMR) late gadolinium enhancement (LGE) and disease severity in Eisenmenger syndrome (ES). This study aimed to explore potential associations between myocardial fibrosis evaluated by the CMR LGE and T1 mapping and risk stratification profiles including exercise tolerance, serum biomarkers, hemodynamics, and right ventricular (RV) function in these patients. METHODS: Forty-five adults with ES and 30 healthy subjects were included. All subjects underwent a contrast-enhanced 3T CMR. Focal replacement fibrosis was visualized on LGE images. The locations of LGE were recorded. After excluding LGE in ventricular insertion point (VIP), ES patients were divided into myocardial LGE-positive (LGE+) and LGE-negative (LGE-) subgroups. Regions of interest in the septal myocardium were manually contoured in the T1 mapping images to determine the diffuse myocardial fibrosis. The relationships between myocardial fibrosis and 6-min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-pro BNP), hematocrit, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance index (PVRI), RV/left ventricular end-systolic volume (RV/LV ESV), RV ejection fraction (RVEF), and risk stratification were analyzed. RESULTS: Myocardial LGE (excluding VIP) was common in ES (16/45, 35.6%), and often located in the septum (12/45, 26.7%). The clinical characteristics, hemodynamics, CMR morphology and function, and extracellular volume fraction (ECV) were similar in the LGE+ and LGE- groups (all P > 0.05). ECV was significantly higher in ES patients (28.6 ± 5.9% vs. 25.6 ± 2.2%, P < 0.05) and those with LGE- ES (28.3 ± 5.9% vs. 25.6 ± 2.2%, P < 0.05) than healthy controls. We found significant correlations between ECV and log NT-pro BNP, hematocrit, mPAP, PVRI, RV/LV ESV, and RVEF (all P < 0.05), and correlations trends between ECV and 6MWT (P = 0.06) in ES patients. An ECV threshold of 29.0% performed well in differentiating patients with high-risk ES from those with intermediate or low risk (area under curve 0.857, P < 0.001). CONCLUSIONS: Myocardial fibrosis is a common feature of ES. ECV may serve as an important imaging marker for ES disease severity.

Comparisons of electrophysiological characteristics, pacing parameters and mid- to long-term effects in right ventricular septal pacing, right ventricular apical pacing and left bundle branch area pacing.

BACKGROUND: As a near-physiological pacing innovation, left bundle branch area pacing (LBBAP) has drawn much attention recently. This study was aimed to investigate the electrophysiological characteristics, unipolar/bipolar pacing parameters and mid- to long-term effects and safety of three different pacing methods and identify possible predictors of adverse left ventricular remodeling. METHODS: Ninety-two patients were divided into the LBBAP group, right ventricular septal pacing (RVSP) group and right ventricular apical pacing (RVAP) group. Baseline information, electrophysiological, pacing and echocardiographic parameters were collected. RESULTS: The three pacing methods were performed with a similar high success rate. The paced QRSd was significantly different among the LBBAP, RVSP and RVAP groups (105.93 ± 15.85 ms vs. 143.63 ± 14.71 ms vs. 155.39 ± 14.17 ms, p < 0.01). The stimulus to left ventricular activation time (Sti-LVAT) was the shortest in the LBBAP group, followed by the RVSP and RVAP groups (72.80 ± 12.07 ms vs. 86.29 ± 8.71 ms vs. 94.14 ± 10.14 ms, p < 0.001). LBBAP had a significantly lower tip impedance during the procedure and 3-month follow up as compared to RVSP and RVAP (p < 0.001). Higher bipolar captured thresholds were observed in LBBAP during the procedure (p < 0.001). Compared to the baseline values, there was a greater reduction in left ventricular end-diastolic dimension (LVEDD) in the LBBAP group (p = 0.046) and a significant enlargement in LVEDD in the RVAP group (p = 0.008). Multiple regression analysis revealed that the Sti-LVAT was a significant predictor of LVEDD at 12 months post-procedure. At the 24-h post-procedure, significant elevations were observed in the cTnI levels in LBBAP (p < 0.001) and RVSP (p < 0.05). More transient RBB injury was observed in LBBAP. But no significant difference was found in cardiac composite endpoints among three groups (p > 0.05). CONCLUSIONS: LBBAP demonstrated a stable captured threshold, a low tip impedance and a high R-wave amplitude during the 12-month follow-up. Left ventricular remodeling was improved at 12 months post-procedure through LBBAP. The Sti-LVAT was a significant predictor of left ventricular remodeling. LBBAP demonstrated its feasibility, effectiveness, safety and some beneficial electrophysiological characteristics during this mid- to long-term follow-up, which should be confirmed by further studies.

C-reactive protein and atrial fibrillation: Insights from epidemiological and Mendelian randomization studies.

BACKGROUND AND AIMS: This study aimed to investigate the role of C-reactive protein (CRP) in atrial fibrillation (AF) from epidemiological and genetic perspectives. METHODS AND RESULTS: Individual-level data from the Kailuan cohort recruited between 2006 and 2017 were included. Serum CRP levels were measured at baseline and at biennial follow-up visits, and incident AF was ascertained from biennial 12-lead ECG assessment and medical records. Cox proportional hazards models were used to assess the association between baseline CRP levels or cumulative exposure to CRP and incident AF. A meta-analysis including nine prospective cohort studies and our current study was also conducted. Mendelian randomization (MR) analysis was performed to evaluate the aetiological role of CRP in AF. In our observational study (n = 86,424), high baseline CRP levels (>3 mg/L), compared with low CRP (<1 mg/L), were not significantly associated with AF risk (HR: 1.18; 95% CI: 0.99-1.40). High cumulative exposure to CRP (HR: 1.49; 95%CI: 1.01-2.21) was significantly associated with an increased risk of AF. Our meta-analysis suggested a positive association between elevated CRP levels and incident AF (relative risk: 1.27; 95% CI: 1.14-1.42). However, no significant association between genetically determined CRP and AF risk was observed in the MR analysis. CONCLUSION: Evidence from observational studies suggested that elevated serum CRP levels were positively associated with incident AF, while the causal effects of CRP on AF were not supported by the MR analysis. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-TNRC-11001489.

Morphological and anatomical characteristics of exserted stigma sterility and the location and function of SlLst (Solanum lycopersicum Long styles) gene in tomato.

KEY MESSAGE: Anatomical changes in and hormone roles of the exserted stigma were investigated, and localization and functional analysis of SlLst for the exserted stigma were performed using SLAF-BSA-seq, parental resequencing and overexpression of SlLst in tomato. Tomato accession T431 produces stigmas under relatively high temperatures (> 27 °C, the average temperature in Harbin, China, in June-August), so pollen can rarely reach the stigma properly. This allows the percentage of male sterility exceed 95%, making the use of this accession practical for hybrid seed production. To investigate the mechanism underlying the exserted stigma male sterility, the morphological changes of, anatomical changes of, and comparative endogenous hormone (IAA, ABA, GA3, ZT, SA) changes in flowers during flower development of tomato accessions DL5 and T431 were measured. The location and function of genes controlling exserted stigma sterility were analyzed using super SLAF-BSA-seq, parental resequencing, comparative genomics and the overexpression of SlLst in tomato. The results showed that an increase in cell number mainly caused stigma exsertion. IAA played a major role, while ABA had an opposite effect on stigma exertion. Moreover, 26 candidate genes related to the exserted stigma were found, located on chromosome 12. The Solyc12g027610.1 (SlLst) gene was identified as the key candidate gene by functional analysis. A subcellular localization assay revealed that SlLst is targeted to the nucleus and cell membrane. Phenotypic analysis of SlLst-overexpressing tomato showed that SlLst plays a crucial role during stigma exsertion.

The α-Subunit of the Chloroplast ATP Synthase of Tomato Reinforces Resistance to Gray Mold and Broad-Spectrum Resistance in Transgenic Tobacco.

Chloroplast ATP synthase (cpATPase) is responsible for ATP production during photosynthesis. Our previous studies showed that the cpATPase CF1 α subunit (AtpA) is a key protein involved in Clonostachys rosea-induced resistance to the fungus Botrytis cinerea in tomato. Here, we show that expression of the tomato atpA gene was upregulated by B. cinerea and Clonostachys rosea. The tomato atpA gene was then isolated, and transgenic tobacco lines were obtained. Compared with untransformed plants, atpA-overexpressing tobacco showed increased resistance to B. cinerea, characterized by reduced disease incidence, defense-associated hypersensitive response-like reactions, balanced reactive oxygen species, alleviated damage to the chloroplast ultrastructure of leaf cells, elevated levels of ATP content and cpATPase activity, and enhanced expression of genes related to carbon metabolism, photosynthesis, and defense. Incremental Ca2+ efflux and steady H+ efflux were observed in transgenic tobacco after inoculation with B. cinerea. In addition, overexpression of atpA conferred enhanced tolerance to salinity and resistance to the fungus Cladosporium fulvum. Thus, AtpA is a key regulator that links signaling to cellular redox homeostasis, ATP biosynthesis, and gene expression of resistance traits to modulate immunity to pathogen infection and provides broad-spectrum resistance in plants in the process.

Optimization of Ultrasonic Flavonoid Extraction from Saussurea involucrate, and the Ability of Flavonoids to Block Melanin Deposition in Human Melanocytes.

(1) Background: Flavonoids are the primary medicinal ingredient of Saussurea involucrate, which have significant antioxidant capacity. Optimizing the extraction of Saussurea involucrate flavonoids (SIFs) and exploring the ability to block melanin deposition caused by reactive oxygen can greatly promote the development of S. involucrate whitening products. (2) Methods: Ultrasonic extraction process was optimized using the Box-Behnken design (BBD) and response surface methodology (RSM). Then, the effect of SIFs on antioxidant activity and anti-deposition of melanin, and genes related to the melanin synthesis are studied. (3) Results: The optimal extraction procedures are as follows: the extraction time, ethanol content, and solvent ratio (v/w) are 64 min, 54%, and 54:1, respectively. The reducing activity and scavenging rates of 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide anion, hydroxyl radical, and ABTS+ were promoted as more S. involucrate flavonoid extract was added. The SIFs extract induced a decrease in the melanin synthesis by inhibiting the human melanoma A375 cell tyrosinase activity. SIFs also depress expression of melanin synthesis related genes. (4) Conclusions: the highest SIFs content was obtained by using 54% ethanol and 54:1 solvent ratio (v/w) for 64 min. The extract of SIFs exhibited good ability of antioxidant and anti-deposition of melanin in human melanocytes.

Darwinian Positive Selection on the Pleiotropic Effects of KITLG Explain Skin Pigmentation and Winter Temperature Adaptation in Eurasians.

Human skin color diversity is considered an adaptation to environmental conditions such as UV radiation. Investigations into the genetic bases of such adaptation have identified a group of pigmentation genes contributing to skin color diversity in African and non-African populations. Here, we present a population analysis of the pigmentation gene KITLG with previously reported signal of Darwinian positive selection in both European and East Asian populations. We demonstrated that there had been recurrent selective events in the upstream and the downstream regions of KITLG in Eurasian populations. More importantly, besides the expected selection on the KITLG variants favoring light skin in coping with the weak UV radiation at high latitude, we observed a KITLG variant showing adaptation to winter temperature. In particular, compared with UV radiation, winter temperature showed a much stronger correlation with the prevalence of the presumably adaptive KITLG allele in Asian populations. This observation was further supported by the in vitro functional test at low temperature. Consequently, the pleiotropic effects of KITLG, that is, pigmentation and thermogenesis were both targeted by natural selection that acted on different KITLG sequence variants, contributing to the adaptation of Eurasians to both UV radiation and winter temperature at high latitude areas.

RE[N(SiMe3)2]3-Catalyzed Guanylation/Cyclization of Amino Acid Esters and Carbodiimides.

The example of rare-earth metal-catalyzed guanylation/cyclization of amino acid esters and carbodiimides is well-established, forming 4(3H)-2-alkylaminoquinazolinones in 65-96% yields. The rare-earth metal amides RE[N(TMS)2]3 (RE = Y, Yb, Nd, Sm, La; TMS = SiMe3) showed high activities, and La[N(TMS)2]3 performed best for a wide scope of the substrates.

Persistent Methyl Orange Degradation Ability of MgAl2O4:(Pr3+,Dy3+)/M-TiO2 Luminescent Photocatalyst.

Metal ions (Cr, Ni, Co) doped titania (M-TiO2) coupled with the long after glow phosphor MgAl2O4:(Pr3+, Dy3+) particles were synthesized by the sol-gel method, with the best mass ratio of MgAl2O4:(Pr3+, Dy3+) to M-TiO2 as 4:6. MgAl2O4:(Pr3+, Dy3+)/M-TiO2 had the persistent methyl orange (MO) photocatalytic degradation ability and the photocatalytic degradation went on reacting more than 90 min in dark after turning off the light. MgAl2O4:(Pr3+, Dy3+) emitted the light as a light source in dark which was absorbed by M-TiO2. The differences of MgAl2O4:(Pr3+, Dy3+)/Cr-TiO2, MgAl2O4:(Pr3+, Dy3+)/Ni-TiO2 and MgAl2O4:(Pr3+, Dy3+)/Co-TiO2 might be attributed to the difference in the metal ions doping. The composite MgAl2O4:(Pr3+, Dy3+)/Cr-TiO2 revealed the highest ability of persistent photocatalytic degradation methyl orange. Different metal ions doping made the TiO2 with different band gap.

[Based on traditional Chinese medicine inheritance support system to analyze the regularity of umbilicus application to treat ascites due to cirrhosis].

Umbilicus application to treat ascites caused by cirrhosis is a simple and effective characteristic therapy. This article analyzed the regularity of application traditional Chinese medicine (TCM) herbs on umbilicus to treat ascites caused by cirrhosis through TCM inherited auxiliary system. This study chose academic literatures related to TCM dressing umbilicus to treat ascites caused by cirrhosis in CNKI database, VIP database, Wanfang database over the past 20 years as the data source, and established database to analyze the core drugs and their channel tropism, property and flavor, compatibility law, and core composition,by means of frequency statistics, and association rules (Apriori method, complicated system entropy clustering). Finally, 92 prescription to treat ascites caused by cirrhosiss were screened out. These prescription includes 109 traditional Chinese medicines. And the analysis showed that there are 14 drugs with usage frequency of 10 and more than 10, 19 common drug pairs, 12 core drug combination. The drugs with high usage frequency include Kansui Radix, Borneolum Syntheticum, Pharbitidis Semen, Rhei Radix et Rhizoma, Moschus, Euphorbiae Pekinensis Radix, Natrii Sulfas, Cinnamomi Cortex, Genkwa Flos, Phytolaccae Radix, Arecae Semen. And the channel which are mostly invoivet includ lung meridian, spleen meridian and kidney meridian; while the property and flavor of the herbs used have the properties of cold and acrid; the common drug pairs include Pharbitidis Semen-Kansui Radix, Borneolum Syntheticum-Kansui Radix, Kansui Radix-Euphorbiae Pekinensis Radix, Kansui Radix-Moschus, Rhei Radix et Rhizome-Kansui Radix, Kansui Radix-Genkwa Flos, Borneolum Syntheticum-Pharbitidis Semen, Borneolum Syntheticum-Pharbitidis Semen-Kansui Radix, Kansui Radix-Arecae Semen; herbs with the function of expelling water and purgation used as main conponents, and resuscitation, promoting the circulation of Qi, and increaseing Yang used as auxilizy conponents.

Occurrence and Genetic Characteristics of Cryptosporidium hominis and Cryptosporidium andersoni in Horses from Southwestern China.

A total of 333 fecal specimens from horses in southwestern China were genotyped based on analysis of the small subunit rRNA (SSU rRNA) gene. Cryptosporidium hominis and Cryptosporidium andersoni were identified in 2 and 4 stool specimens, respectively. The identification of C. hominis was confirmed by sequence analysis of the 70-kDa heat shock protein (HSP70) and oocyst wall protein (COWP) genes. Subtyping analysis of the 60-kDa glycoprotein (GP60) gene sequence of C. hominis revealed a new rare subtype Id, named IdA15; only three Id isolates have been reported in humans to date. Multilocus sequence typing (MLST) analysis indicated that the C. andersoni subtype was A6, A5, A2, and A1 at the four minisatellite loci (MS1, MS2, MS3, and MS16, respectively). This is the first report to identify the presence of C. andersoni and C. hominis in horses in southwestern China and the first to identify a rare zoonotic subtype Id of C. hominis in horses. These findings suggest that infected horses may act as potential reservoirs of Cryptosporidium to transmit infections to humans.

Plastid DNA insertions in plant nuclear genomes: the sites, abundance and ages, and a predicted promoter analysis.

The transfer of plastid DNA sequences into plant nuclear genomes plays an important role in the genomic evolution of plants. The abundance of nuclear-localized plastid DNA (nupDNA) correlates positively with nuclear genome size, but the genetic content of nupDNA remains unknown. In this mini review, we analyzed the number of nuclear-localized plastid gene fragments in known plant genomic data. Our analysis suggests that nupDNAs are abundant in plant nuclear genomes and can include multiple complete copies of protein-coding plastid genes. Mutated nuclear copies of plastid genes contained synonymous and nonsynonymous substitutions. We estimated the age of the nupDNAs based on the time when each integration occurred, which was calculated by comparing the nucleotide substitution rates of the nupDNAs and their respective plastid genes. These data suggest that there are two distinct age distribution patterns for nupDNAs in plants, and Oryza sativa and Zea mays were found to contain a very high proportion of young nupDNAs. Expressed sequence tags and predicted promoters of nupDNAs were identified, revealing that certain nuclear-localized plastid genes may be functional and that some have undergone positive natural selection pressure.