[Effect of bird-induced anus-lifting surgery combined with oral Relinqing Granules on LUTS/CP with damp heat syndrome: Evaluation by infrared thermal imaging].

OBJECTIVE: To observe the clinical effect of bird-induced anus-lifting surgery (BIAL) combined with oral Relinqing Granules (RG) in the treatment of lower urinary tract symptoms / chronic prostatitis (LUTS/CP) with damp-heat syndrome using infrared thermal imaging (ITI). METHODS: This study included 165 cases of LUTS/CP with damp-heat syndrome treated in the Departments of Andrology and Urology of our hospital, which were divided into three groups of an equal number and treated by medication of oral tamsulosin hydrochloride at 0.2 mg, qd plus levofloxacin at 0.2 g bid (control), anus-lifting exercise (15 lifts once a day) combined with oral RG at 8 g tid (routine treatment) and BIAL (15 lifts once a day) combined with oral RG at 8 g tid (BIAL+RG), respectively, all for two weeks. We recorded the ITI indicators, NIH-CPSI and Self-Rating Anxiety Scale (SAS) scores of patients before and after treatment, observed adverse reactions during the treatment, and compared them among the three groups of patients. RESULTS: Compared with the baseline, NIH-CPSI and SAS scores were significantly reduced in all the three groups after treatment (P < 0.05), even more significantly in the BIAL+RG (10.49 ± 2.97 and 49.73 ± 2.79) than in the control (21.15 ± 3.56 and 52.62 ± 5.38) and routine treatment groups (15.55 ± 2.77 and 52.35 ± 3.87) (P < 0.05). The ITI temperature at the related parts of the body was remarkably decreased in the three groups after treatment (P < 0.05), even lower in the BIAL+RG group (30.47 ± 1.61, 32.14 ± 1.25, 31.16 ± 1.58, 31.97 ± 1.19) than in the control (33.39 ± 0.6, 33.64 ± 1.07, 32.78 ± 0.58, 33.18 ± 0.78) and routine treatment groups (31.93 ± 1.14, 33.06 ± 0.8, 33.08 ± 0.82, 33.17 ± 1.05) (P < 0.05), with statistically significant difference from the baseline in the BIAL+RG group after 12 hours and 24 hours of treatment (ï¼»34.26 ± 0.06ï¼½ vs ï¼»32.65 ± 0.05ï¼½ and ï¼»32.72 ± 0.09ï¼½, P < 0.05), but not between the two time points (P > 0.05). The incidence rate of adverse reactions was markedly lower in the BIAL+RG and routine treatment groups than in the control (P < 0.05) but not significantly different between the BIAL+RG and routine treatment groups (P > 0.05). CONCLUSION: Bird-induced anus-lifting surgery combined with oral Relinqing Granules can safely and significantly improve infrared thermal imaging indicators and NIH-CPSI scores in LUTS/CP patients with damp-heat syndrome.

Repair mechanism of Yishen Tongluo formula on mouse sperm DNA fragmentation caused by polystyrene microplastics.

CONTEXT: Plastics can break down into millions of microplastic (MPs, < 5 mm) particles in the soil and ocean. These MPs can then affect the function of the reproductive system. There is currently no effective solution to this problem aside from traditional Chinese medicine. We have previously used Yishen Tongluo formula (YSTL) to treat sperm DNA damage caused by some toxic substances. OBJECTIVE: To investigate the mechanism underlying the repair of mouse sperm DNA fragmentation caused by polystyrene microplastics by YSTL. MATERIALS AND METHODS: An animal model of polystyrene microplastic (PS-MP)-induced sperm DNA damage was replicated by gavage of SPF ICR (CD1) mice PS-MPs at 1 mg/d and treated with YSTL at 11.89, 23.78 and 47.56 g/kg, respectively, for 60 days. The Sperm DNA fragmentation index (DFI) of each group was detected and compared. The target genes of YSTL identified by transcriptomic and proteomic analyses were validated by qRT-PCR and western blotting. RESULTS: The DFI of the PS group (20.66%) was significantly higher than that of the control group (4.23%). The medium and high doses of the YSTL group (12.8% and 11.31%) exhibited a significant repairing effect. The most enriched pathway was PI3K/Akt. TBL1X, SPARC, hnRNP0, Map7D1, Eps8 and Mrpl27 were screened and SPARC was validated. DISCUSSION AND CONCLUSIONS: The precise mechanism by which YSTL inhibits PD-MPs DNA damage may be associated with the PI3K/Akt pathway and SPARC. It provides a new direction for using traditional Chinese medicine to prevent and repair reproductive system injury caused by MPs.

A tissue-specific profile of miRNAs and their targets related to paeoniaflorin and monoterpenoids biosynthesis in Paeonia lactiflora Pall. by transcriptome, small RNAs and degradome sequencing.

Paeonia lactiflora Pall. (Paeonia) has aroused many concerns due to its extensive medicinal value, in which monoterpene glucoside paeoniflorin and its derivatives are the active chemical components. However, little is known in the molecular mechanism of monoterpenoids biosynthesis, and the regulation network between small RNAs and mRNAs in monoterpenoids biosynthesis has not been investigated yet. Herein, we attempted to reveal the tissue-specific regulation network of miRNAs and their targets related to paeoniaflorin and monoterpenoids biosynthesis in Paeonia by combining mRNA and miRNA expression data with degradome analysis. In all, 289 miRNAs and 30177 unigenes were identified, of which nine miRNAs from seven miRNA families including miR396, miR393, miR835, miR1144, miR3638, miR5794 and miR9555 were verified as monoterpenoids biosynthesis-related miRNAs by degradome sequencing. Moreover, the co-expression network analysis showed that four monoterpenoids-regulating TFs, namely AP2, MYBC1, SPL12 and TCP2, were putatively regulated by five miRNAs including miR172, miR828, miR858, miR156 and miR319, respectively. The present study will improve our knowledge of the molecular mechanisms of the paeoniaflorin and monoterpenoids biosynthesis mediated by miRNA to a new level, and provide a valuable resource for further study on Paeonia.

Clinical study of Wuwei Fuzheng Yijing formula in the treatment of sperm DNA damage in male infertility: A study protocol for a randomized controlled trial.

BACKGROUND: The incidence of male infertility is increasing in recent years, and the semen routine examination of some patients is normal, but the semen pathological examination shows that the sperm DNA fragmentation index (DFI) is high, and the patients' clinical manifestations are infertility or recurrent abortion of their spouses. At present, there is no special treatment for male infertility caused by high DFI, and traditional Chinese medicine compound prescription shows potential value in the treatment of male infertility. Wuwei Fuzheng Yijing formula (WFY) is an effective prescription for the treatment of sperm DNA damage in male infertility, but there is no strict clinical trial to support its application. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of WFY in patients with sperm DNA damage in male infertility. METHODS: In this randomized controlled study, 100 patients who met the inclusion criteria were randomly divided into WFY group and levocarnitine oral solution group. The treatment period was 12 weeks. The main observation index was sperm DFI, and the secondary observation index was sperm concentration, motility, survival rate, and TCM syndrome score. Safety observation indicators will include electrocardiogram, blood tests (including blood routine tests, liver and renal function), routine urine tests, and routine stool tests. All results were evaluated at the 4th and 8th week of the baseline, and the end of treatment. DISCUSSION: This study will provide a basis for the efficacy and safety of WFY in the treatment of sperm DNA damage in male infertility with spleen and kidney qi deficiency and blood stasis.

Transcriptomic and proteomic characteristics of the di(2-ethylhexyl) phthalate-induced sperm dna damage mouse model.

Di(2-ethylhexyl) phthalate (DEHP) is one of the most common organic pollutants and is added to various plastic products as a plasticizer. DEHP oxidative metabolite content in the human body is associated with DNA damage in sperm and decreased testosterone levels in blood. In this study, a DEHP-induced sperm DNA damage mouse model was replicated and improved, and the transcriptomic and proteomic characteristics of the model were observed. Male mice in the two groups were exposed to DEHP 1 g/kg/d or the same amount of normal saline for 60 days, and the sperm DNA fragmentation index (DFI) was detected by a sperm chromatin structure assay (SCSA). The mRNA and protein expression profiles of the testis were detected by RNA-seq and data-independent acquisition (DIA). The sperm DFI of the DEHP group was significantly increased. Compared with the control group, 111 differentially expressed genes (DEGs) and 2147 differentially expressed proteins (DEPs), such as Lamb2, Ahnak, Tkt, Dnah8 and Tbl2, were found in the DEHP group. These genes were mainly enriched in metabolic pathways, pathways in cancer and the PI3K-Akt signaling pathway. Our results showed that DEHP 1 g/kg/d can induce sperm DNA damage in a male mouse model after 60 days of intragastric administration. The reproductive toxicity of DEHP may be related to metabolic pathways in cancer and the PI3K-Akt signaling pathway.

Repair mechanism of Wuwei Fuzheng Yijing formula in di-2-ethylhexyl phthalate-induced sperm DNA fragmentation in mice.

CONTEXT: Di-2-ethylhexyl phthalate (DEHP), a known persistent organic pollutant, can increase the sperm DNA fragmentation index (DFI). OBJECTIVE: To investigate the mechanism underlying the repair of DEHP-induced sperm DNA damage in mice by Wuwei Fuzheng Yijing (WFY) formula. MATERIALS AND METHODS: The potential targets of WFY and sperm DNA fragment (SDF) were obtained from the TCMSP, BATMAN-TCM, OMIM and GeneCards. The protein-protein interaction (PPI) network, GO and KEGG pathway analyses of WFY-SDF were constructed. An animal model of DEHP-induced sperm DNA damage was replicated by gavage of SPF ICR (CD1) mice DEHP at 1 g/kg/d and treated with WFY at 8.92, 17.84 and 35.67 g/kg, respectively, for 60 d. Sperm DFI of each group was detected and compared. The target genes of WFY identified by transcriptomic and proteomic analyses were validated by qRT-PCR and Western blotting. RESULTS: Network pharmacology pathway analysis indicated that PI3K/Akt was the potential target of WFY on SDF. The DFI of the DEHP group (25.48%) was significantly higher than that of the control group (4.02%). The high-dose WFY group (19.05%) exhibited the most significant repairing effect. The related pathways were PI3K/Akt and metabolic. Aass, Aldh1a7, GSTA3, betaine homocysteine S-methyltransferase (Bhmt), Mug2 and Svs1 were screened and Bhmt was validated. DISCUSSION AND CONCLUSIONS: WFY can repair sperm DNA damage caused by DEHP, and the mechanism may be related to PI3K/Akt and metabolic pathways, and Bhmt. This provides a new direction for using traditional Chinese medicine to prevent and repair reproductive system injury caused by pollutants.

[Huayu Jiedu Shengjing Decoction improves semen quality and reduces TCM syndrome scores in patients with varicocele-induced asthenospermic infertility].

OBJECTIVE: To observe the clinical efficacy of "Huayu Jiedu Shengjing Decoction" (HJSD) in the treatment of varicocele (VC)-induced asthenospermic infertility and its action mechanism. METHODS: Using computer-generated random numbers, we equally divided 88 patients meeting the study criteria into an experimental and a control group, the former treated orally with HJSD plus or minus, while the latter with Maizhiling Tablets and levocarnitine, both for a course of 12 weeks. After medication, we obtained TCM syndrome scores, sperm motility, sperm DNA fragmentation index (DFI), the seminal cord venous ultrasonographic index, and levels of nitric oxide (NO), reactive oxygen species (ROS) and superoxide dismutase (SOD) in the seminal plasma from the patients, compared the therapeutic effects between the two groups, and analyzed the correlation among the obtained parameters. RESULTS: The total effectiveness rate was dramatically higher in the experimental than in the control group (86.04% vs 73.74%, P < 0.01). The TCM syndromes scores, sperm motility, sperm DFI, and seminal plasma NO, ROS and SOD were all more significantly improved in the former than in the latter group (P < 0.05). CONCLUSION: Huayu Jiedu Shengjing Decoction can improve semen quality and reduce TCM syndrome scores without adverse reactions in patients with VC-induced asthenospermic infertility, which may be attributed to its effect of improving antioxidation and local blood flow.

[Yishen Tongluo Prescription for repairing benzo(a)pyrene-induced sperm DNA damage in male rats: Effect and mechanism].

OBJECTIVE: To investigate the repairing effect of Yishen Tongluo Prescription (YTP) on sperm DNA fragmentation index (DFI) in male rats exposed to benzo(a)pyrene (BaP) and its possible mechanism. METHODS: Thirty Wistar male rats were equally randomized into a blank control, a BaP-exposure and a YTP intervention group, those in the latter two groups exposed to BaP at 20 mg/kg/d for 60 consecutive days, and those in the YTP intervention group treated intragastrically with YTP from the 31st day of BaP exposure for a total of 30 days. After the last administration, the sperm DFI of the rats was detected by sperm chromatin structure analysis, the levels of FSH, LH and T in the serum and superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO) and adenosine triphosphate (ATP) in the testis were measured by ELISA. RESULTS: Compared with the blank controls, the rats in the BaP-exposure group showed significantly increased DFI ( ï¼»4.23 ± 1.40ï¼½% vs ï¼»12.46 ± 3.07ï¼½%, P < 0.05), serum FSH (ï¼»1.76 ± 0.31ï¼½ vs ï¼»2.53 ± 0.28ï¼½ U/L, P < 0.05) and LH (ï¼»30.59 ± 2.14ï¼½ vs ï¼»39.72 ± 2.80ï¼½ U/L, P < 0.05), decreased levels of serum T (ï¼»5.33 ± 0.43ï¼½ vs ï¼»4.42 ± 0.38ï¼½ nmol/L, P < 0.05) and testicular SOD (ï¼»166.18 ± 3.74ï¼½ vs ï¼»113.23 ± 10.76ï¼½ U/ml, P < 0.05) and ATP (ï¼»41.23 ± 2.21ï¼½ vs ï¼»33.48 ± 2.74ï¼½ mol/L, P < 0.05), and elevated contents of MDA (ï¼»7.55 ± 0.93ï¼½ vs ï¼»10.59 ± 1.17ï¼½ nmol/ml, P < 0.05) and NO (ï¼»44.23±4.47ï¼½ vs ï¼»54.49 ± 3.13ï¼½ mol/L, P < 0.05). All the above parameters returned to normal after YTP intervention (DFI: ï¼»5.73 ± 2.46ï¼½%, FSH: ï¼»2.07 ± 0.45ï¼½ U/L, LH: ï¼»33.94 ± 4.44ï¼½ U/L, T: ï¼»4.96 ± 0.24ï¼½ nmol/L, SOD: ï¼»135.22 ± 7.26ï¼½ U/ml, ATP: ï¼»38.26 ± 2.14ï¼½ mol/L, MDA: ï¼»8.37 ± 1.29ï¼½ nmol/ml, NO: ï¼»48.36 ± 3.98ï¼½ mol/L), with statistically significant difference from those in the BaP-exposure group (all P < 0.05). CONCLUSION: Yishen Tongluo Prescription can repair BaP-induced sperm DNA damage in male rats, which may be attributed to its effects of suppressing oxidative damage.

Lineage Divergence and Vector-Specific Adaptation Have Driven Chikungunya Virus onto Multiple Adaptive Landscapes.

Previous studies have shown that the adaptation of Indian Ocean lineage (IOL) chikungunya virus (CHIKV) strains for Aedes albopictus transmission was mediated by an E1-A226V substitution, followed by either a single substitution in E2 or synergistic substitutions in the E2 and E3 envelope glycoproteins. Here, we examined whether Asian lineage strains, including those that descended from the 2014 Caribbean introduction, are likely to acquire these A. albopictus-adaptive E2 substitutions. Because Asian lineage strains cannot adapt through the E1-A226V substitution due to an epistatic constraint, we first determined that the beneficial effect of these E2 mutations in IOL strains is independent of E1-A226V. We then introduced each of these E2 adaptive mutations into the Asian lineage backbone to determine if they improve infectivity for A. albopictus. Surprisingly, our results indicated that in the Asian lineage backbone, these E2 mutations significantly decreased CHIKV fitness in A. albopictus. Furthermore, we tested the effects of these mutations in Aedes aegypti and observed different results from those in A. albopictus, suggesting that mosquito species-specific factors that interact with the envelope proteins are involved in vector infection efficiency. Overall, our results indicate that the divergence between Asian lineage and IOL CHIKVs has led them onto different adaptive landscapes with differing potentials to expand their vector host range. IMPORTANCE Since its introduction into the Caribbean in October 2013, CHIKV has rapidly spread to almost the entire neotropical region. However, its potential to further spread globally, including into more temperate climates, depends in part on its ability to be transmitted efficiently by Aedes albopictus, which can survive colder winters than A. aegypti. We examined in an Asian lineage backbone A. albopictus-adaptive mutations that arose from 2005 to 2009 in Indian Ocean lineage (IOL) strains. Our results predict that the Asian CHIKV lineage now in the Americas will not readily adapt for enhanced A. albopictus transmission via the same mechanisms or adaptive mutations used previously by IOL strains. The vector species- and CHIKV lineage-specific effects caused by adaptive CHIKV envelope glycoprotein substitutions may elucidate our understanding of the mechanisms of mosquito infection and spread.

Naked-Eye Detection of Hepatitis B Surface Antigen Using Gold Nanoparticles Aggregation and Catalase-Functionalized Polystyrene Nanospheres.

Developing rapid, efficient, highly sensitive, simple, stable, and low-cost virus marker detection products that are appropriate for basic facilities is of great importance in the early diagnosis and treatment of viruses. Naked-eye detection methods are especially important when medical testing facilities are limited. Polystyrene nanospheres (PSs) with catalytic and specific recognition functions were successfully developed by simultaneously modifying catalase and goat anti-hepatitis B surface antibodies on nanospheres. The modified PSs contributed significantly to the amplification of the signal. Via the specific antigen-antibody reaction, the bifunctional nanospheres could be captured on microplate and then catalyzed the decomposition of hydrogen peroxide to reduce chloroauric acid and synthesize gold nanoparticles (AuNPs). Due to the surface plasmon resonance of AuNPs, the solution color change could be observed with the naked eye and the limit of detection (LOD) was 0.1 ng/mL. Furthermore, the LOD observed with instrumentation was 0.01 ng/mL, which meant that a rapid, efficient, and highly sensitive method for the detection of hepatitis B surface antigens was successfully developed, and neither complex sample pretreatment nor expensive equipment was needed.

One-step synthesis of fluorescence-enhanced carbon dots for Fe (III) on-off-on sensing, bioimaging and light-emitting devices.

Carbon quantum dots (CDs), as one of the most potential fluorescent sensing materials, have attracted lots of attention in recent years. However, the low quantum yields, complicated separation and purification procedures have limited its application and large-scale production. In this paper, a facile and universal method was successfully developed to synthesize CDs-silica (SiO2) spheres composites (CS composites), which not only demonstrates 10-fold fluorescence enhancement compared with single CDs but also enables the purification with a simple centrifugation step. Meanwhile, fabricated composites also presented superior photoluminescence (PL) stability and high PL intensity, even in some tough environments such as acid/alkali aqueous solution, high/low temperature, and high ion concentration aqueous solution. This simple, fast, low-cost, and efficient synthesis method would potentially expand the application of CDs for clinical analysis, optical sensing (ferric ion (Fe3+) and pyrophosphate), bioimaging and light-emitting diodes (LEDs).

Novel Graphene Oxide Nanohybrid Doped Methacrylic Acid Hydrogels for Enhanced Swelling Capability and Cationic Adsorbability.

Novel versatile hydrogels were designed and composited based on covalent bond and noncovalent bond self-assembly of poly(methacrylic acid) (PMAA) networks and nanohybrids doped with graphene oxide (GO). The structures and properties of the neat PMAA and the prepared PMAA/GO hydrogels were characterized and analyzed in detail, using X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, swelling and cationic absorption, etc. The swelling results showed that the water penetration follows the non-Fick transport mechanism based on swelling kinetics and diffusion theory. The swelling capacity of PMAA and composited PMAA/GO hydrogels toward pH, Na+, Ga2+, and Fe3+ was investigated; the swelling ratio was tunable between 4.44 and 36.44. Taking methylene blue as an example, the adsorption capacity of PMAA/GO hydrogels was studied. Nanohybrid doped GO not only self-associated with PMAA via noncovalent bonding interactions and had a tunable swelling ratio, but also interacted with water molecules via electrostatic repulsion, offering a pH response of both the network and dye absorption. Increases in pH caused a rise in equilibrium swelling ratios and reduced the cumulative cationic dye removal.

A fluorometric and colorimetric dual-signal nanoplatform for ultrasensitive visual monitoring of the activity of alkaline phosphatase.

Considering the limited sensitivity and accuracy of single-signal assay strategies, the multi-signal assay strategy has sparked significant excitement in recent years. In this study, for the first time, we reported a one-pot method in situ synthesis of carbon-containing nanoparticles (CNPs) via p-aminophenol (AP) and diethylenetriamine (DETA). The CNP solution exhibits yellow and light blue fluorescence under UV-light. Moreover, the CNPs exhibited excellent photoluminescence stability even under extreme conditions. Inspired by the alkaline phosphatase (ALP)-triggered specific catalytic reaction, we constructed an ultrasensitive fluorescence and colorimetric two-channel strategy for monitoring the ALP activity. By optimizing the detection parameters, the detection limits for both fluorometric and colorimetric were 0.05 mU mL-1. Moreover, the strategy showed high specificity and was successfully applied to monitor the ALP activity level in human serum samples. The analytical strategy opened a new window for the detection of the ALP activity, screening of the ALP inhibitor, and disease diagnosis.

Water-stable perovskite-on-polymer fluorescent microspheres for simultaneous monitoring of pH, urea, and urease.

Perovskite materials have attracted attention due to their excellent optical and electrical properties; however, their unsatisfactory stability limits their application in biochemical detection. In this paper, CsPbBr3 perovskite quantum dots were successfully encapsulated in poly(styrene/acrylamide) microspheres, using a swelling-shrinking method. The manufactured perovskite microspheres (PDPS composites) not only maintained strong photoluminescence (PL) stability but also demonstrated great water solubility. Additionally, a real-time pH monitoring platform was constructed based on the prepared PDPS composites and dopamine, and the system showed a good linear relationship in a pH range of 4-12. Furthermore, urea could be hydrolyzed to produce hydroxyl groups, thereby increasing the pH of the solution. Therefore, this system was then extended for urea and urease detection. As a result, the detection limits of urea and urease were recorded as 1.67 µM and 2.1 mU/mL, respectively. This development provides an interesting demonstration of the expanding list of applications of perovskite materials.

Yishentongluo decoction in treatment of idiopathic asthenozoospermia infertility: Study protocol for a randomized controlled trial.

BACKGROUND: The reproductive dilemma faced by men has always been the focus of the whole society. Idiopathic asthenozoospermia (AZS), as one of the common causes of male infertility, lack of specific treatment. Traditional Chinese medicine has shown potential benefits in the management of male infertility. Yishentongluo decoction (YSTL) is a representative Chinese herbal formula; however, there is still no rigorous clinical trial supporting its application. Therefore, we designed a randomized controlled trial to evaluate the efficacy and safety of YSTL for patients with idiopathic AZS and explain the possible action mechanisms of YSTL in improving sperm motility. METHODS: In this randomized controlled study, a total of 160 eligible patients will be assigned to YSTL group or the Levocarnitine oral solution group in a 1:1 ratio. The treatment period will be 12 weeks and the follow-up period will last 4 weeks. The primary outcome will be the the progressive (motility), sperm rate (%). Secondary outcomes will include the progressive (motility) + non-progressive (motility) sperm rate(%), total effective sperm count, inner mitochondrial membrane potential (MMP) in spermatozoa, and spouse pregnancy rate (%). Safety outcomes will cover electrocardiogram , blood tests (including blood routine test, hepatic function, and renal function), urine routine test, and stool routine test. The semen parameters, sperm MMP test, and all the safety outcomes will be performed at the baseline, 4th, 8th and 12th week. The pregnancy outcome will be evaluated at 4 weeks after treatment. DISCUSSION: This study will provide initial evidence regarding the efficacy and safety of YSTL in the treatment of idiopathic AZS with kidney deficiency and blood stasis pattern. In addition, potential mechanisms of YSTL in improving sperm motility will be explored based on sperm MMP test. TRIAL REGISTRATION: Chinese Clinical Trials Register identifier, ChiCTR2000033290, registered on 26 May 2020.

A Zika virus envelope mutation preceding the 2015 epidemic enhances virulence and fitness for transmission.

Arboviruses maintain high mutation rates due to lack of proofreading ability of their viral polymerases, in some cases facilitating adaptive evolution and emergence. Here we show that, just before its 2013 spread to the Americas, Zika virus (ZIKV) underwent an envelope protein V473M substitution (E-V473M) that increased neurovirulence, maternal-to-fetal transmission, and viremia to facilitate urban transmission. A preepidemic Asian ZIKV strain (FSS13025 isolated in Cambodia in 2010) engineered with the V473M substitution significantly increased neurovirulence in neonatal mice and produced higher viral loads in the placenta and fetal heads in pregnant mice. Conversely, an epidemic ZIKV strain (PRVABC59 isolated in Puerto Rico in 2015) engineered with the inverse M473V substitution reversed the pathogenic phenotypes. Although E-V473M did not affect oral infection of Aedes aegypti mosquitoes, competition experiments in cynomolgus macaques showed that this mutation increased its fitness for viremia generation, suggesting adaptive evolution for human viremia and hence transmission. Mechanistically, the V473M mutation, located at the second transmembrane helix of the E protein, enhances virion morphogenesis. Overall, our study revealed E-V473M as a critical determinant for enhanced ZIKV virulence, intrauterine transmission during pregnancy, and viremia to facilitate urban transmission.

Carbon dots-based dual-emission ratiometric fluorescence sensor for dopamine detection.

The detection of Dopamine (DA) is significant for disease surveillance and prevention. However, the development of the precise and simple detection techniques is still at a preliminary stage due to their high tester requirements, time-consuming process, and low accuracy. In this work, we present a novel dual-emission ratiometric fluorescence sensing system based on a hybrid of carbon dots (CDs) and 7-amino-4-methylcoumarin (AMC) to quickly monitor the DA concentration. Linked via amide bonds, the CDs and AMC offered dual-emissions with peaks located at 455 and 505 nm, respectively, under a single excitation wavelength of 300 nm. Attributed to the fluorescence of the CDs and AMC in the nanohybrid system can be quenched by DA, the concentration of DA could be quantitatively detected by monitoring the ratiometric ratio change in fluorescent intensity. More importantly, the CDs-AMC-based dual-emission ratiometric fluorescence sensing system demonstrated a remarkable linear relationship in the range of 0-33.6 µM to detection of DA, and a low detection limit of 5.67 nM. Additionally, this sensor successfully applied to the detection of DA in real samples. Therefore, the ratiometric fluorescence sensing system may become promising to find potential applications in biomedical dopamine detection.

Chikungunya Virus: Role of Vectors in Emergence from Enzootic Cycles.

Chikungunya virus (CHIKV), a re-emerging mosquito-borne arbovirus, has caused millions of cases of severe, often chronic arthralgia during recent outbreaks. In Africa, circulation in sylvatic, enzootic cycles involves several species of arboreal mosquito vectors that transmit among diverse nonhuman primates and possibly other amplifying hosts. Most disease occurs when CHIKV emerges into a human-amplified cycle involving Aedes aegypti and sometimes Aedes albopictus transmission and extensive spread via travelers. Epidemiologic studies suggest that the transition from enzootic to epidemic cycles begins when people are infected via spillover in forests. However, efficient human amplification likely only ensues far from enzootic habitats where peridomestic vector and human densities are adequate. Recent outbreaks have been enhanced by mutations that adapt CHIKV for more efficient infection of Ae. albopictus, allowing for geographic expansion. However, epistatic interactions, sometimes resulting from founder effects following point-source human introductions, have profound effects on transmission efficiency, making CHIKV emergence somewhat unpredictable.

[Luobufukebiri Pills improve semen quality and seminal plasma-related biochemical indexes in patients with asthenospermia].

OBJECTIVE: To investigate the clinical effect of Luobufukebiri Pills (LP) on asthenospermia and its action mechanism. METHODS: A total of 206 patients with asthenospermia in Henan Provincial Hospital of Traditional Chinese Medicine from March 2018 to December 2018 were randomly assigned to receive oral LP (the experimental group, n = 103) bid 10 pills each time or vitamin E soft capsules (the control group, n = 103) bid 100 mg each time for a course of 12 weeks. We compared the semen volume, sperm concentration, sperm motility, levels of α-glucosidase (α-Glu), fructose (Fru), malondialdehyde (MDA) and superoxide dismutase (SOD) in the seminal plasma, and the number of pregnancies between the two groups of patients before and after treatment. RESULTS: All the patients finished the experiment except 1 in the control group due to personal reasons. After 12 weeks of medication, the patients in the experimental group showed significant increases over the baseline in sperm concentration (ï¼»36.27 ± 11.05ï¼½ vs ï¼»25.96 ± 8.63ï¼½ ×106/ml, P < 0.05), grade a sperm (ï¼»16.92 ± 5.72ï¼½% vs ï¼»9.34 ± 3.18ï¼½%, P < 0.05), grade a+b sperm (ï¼»36.08 ± 6.84ï¼½% vs ï¼»19.88 ± 4.65ï¼½%, P < 0.05), total sperm motility (ï¼»50.37 ± 10.38ï¼½% vs ï¼»24.62 ± 6.12ï¼½%, P < 0.05), and the levels of α-Glu (ï¼»46.94 ± 9.16ï¼½ vs ï¼»32.25 ± 8.30ï¼½ U/ml, P < 0.05), Fru (ï¼»28.08 ± 5.72ï¼½ vs ï¼»16.38 ± 4.62ï¼½ µmol/ml, P < 0.05) and SOD (ï¼»182.28 ± 18.44ï¼½ vs ï¼»100.37 ± 10.22ï¼½ U/ml, P < 0.05), but a decrease in the content of seminal plasma MDA (ï¼»10.37 ± 2.93ï¼½ vs ï¼»15.62 ± 4.68ï¼½ nmol/ml, P < 0.05). Increases were also observed in the control group over the baseline in grade a sperm (ï¼»12.40 ± 6.33ï¼½% vs ï¼»9.26 ± 2.94ï¼½%, P < 0.05), grade a+b sperm (ï¼»25.42 ± 5.24ï¼½% vs ï¼»19.43 ± 4.17ï¼½%, P < 0.05), total sperm motility (ï¼»40.22 ± 9.72ï¼½% vs ï¼»23.99 ± 5.77ï¼½%, P < 0.05), and levels of α-Glu (ï¼»40.31 ± 8.22ï¼½ vs ï¼»31.06 ± 7.51ï¼½ U/ml, P < 0.05) and SOD (ï¼»139.71 ± 14.08ï¼½ vs ï¼»102.11 ± 9.24ï¼½ U/ml, P < 0.05), but a decrease in the content of seminal plasma MDA (ï¼»12.72 ± 3.11ï¼½ vs ï¼»15.62 ± 4.68ï¼½ nmol/ml, P < 0.05). The total clinical effectiveness rate was remarkably higher in the experimental than in the control group (87.38% vs 58.82%, P < 0.05). CONCLUSIONS: Luobufukebiri Pills are safe and effective for the treatment of asthenospermia, which may be attributed to their ability of improving oxidative stress damage.

Molecular Epidemiology of Dengue in Panama: 25 Years of Circulation.

Dengue virus (DENV) is the most prevalent arbovirus in terms of human public health importance globally. In addition to DENV epidemiological surveillance, genomic surveillance may help investigators understand the epidemiological dynamics, geographic distribution, and temporal patterns of DENV circulation. Herein, we aimed to reconstruct the molecular epidemiology and phylogeny of DENV in Panama to connect the epidemiological history of DENV dispersal and circulation in Latin America. We retrospectively analyzed the epidemiological data obtained during 25 years of DENV surveillance in Panama. DENV was reintroduced in Panama in 1993 after a 35 year absence of autochthonous transmission. The increase in the number of total dengue cases has been accompanied by an increase in severe and fatal cases, with the highest case fatality rate recorded in 2011. All four serotypes were detected in Panama, which is characterized by serotype replacement and/or co-circulation of multiple serotypes. Phylogenetic analysis of datasets collected from envelope (E) gene sequences obtained from viruses isolated from human sera demonstrated that circulating viruses were highly diverse and clustered in distinct clades, with co-circulation of clades from the same genotype. Our analyses also suggest that Panamanian strains were related to viruses from different regions of the Americas, suggesting a continuous exchange of viruses within the Americas.