Fast freezing inhibits melanin synthesis of melanocytes by modulating the Wnt/ß-catenin signalling pathway.

Skin hyperpigmentation is mainly caused by excessive synthesis of melanin; however, there is still no safe and effective therapy for its removal. Here, we found that the dermal freezer was able to improve UVB-induced hyperpigmentation of guinea pigs without causing obvious epidermal damage. We also mimic freezing stimulation at the cellular level by rapid freezing and observed that freezing treatments <2.5 min could not decrease cell viability or induce cell apoptosis in B16F10 and Melan-A cells. Critically, melanin content and tyrosinase activity in two cells were greatly reduced after freezing treatments. The dramatic decrease in tyrosinase activity was associated with the downregulation of MITF, TYR, TRP-1 and TRP-2 protein expression in response to freezing treatments for two cells. Furthermore, our results first demonstrated that freezing treatments significantly reduced the levels of p-GSK3ß and ß-catenin and the nuclear accumulation of ß-catenin in B16F10 and Melan-A cells. Together, these data suggest that fast freezing treatments can inhibit melanogenesis-related gene expression in melanocytes by regulating the Wnt/ß-catenin signalling pathway. The inhibition of melanin production eventually contributed to the improvement in skin hyperpigmentation induced by UVB. Therefore, fast freezing treatments may be a new alternative of skin whitening in the clinic in the future.

Three Novel Rhodamine 6G-Based Colorimetric and Fluorescent pH Switches.

Three rhodamine 6G derivatives (REHA, RETA and REDA) were designed and synthesized by connecting rhodamine 6G and 3-methyl-2-thiophenal with hydrazine hydrate, ethylenediamine and diethylenetriamine, respectively. In CH3CN/H2O (50/50, v/v), the absorbance of REHA, RETA and REDA at 528 nm was suddenly enhanced by 3.2, 3.8 and 7.2 times within the pH range of 3.03-2.31, 3.05-2.32 and 3.06-2.34, respectively, and the solution changed from colorless to pink. Meanwhile, the maximal fluorescence intensity sharply increased by 53.9, 26.6 and 24.9 times in the pH range of 3.86-3.46, 3.88-3.47 and 3.89-3.48, respectively, and the solution changed from dark to bright yellow-green fluorescence. REHA, RETA and REDA can act as highly selective and sensitive colorimetric and fluorescent pH switches with good recyclability and anti-interference ability. The response mechanism of REHA, RETA and REDA to pH was studied by 1H NMR spectroscopy, and their application in indicating small pH changes in dyeing wastewater was investigated.

Glutathione-depleting Liposome Adjuvant for Augmenting the Efficacy of a Glutathione Covalent Inhibitor Oridonin for Acute Myeloid Leukemia Therapy.

BACKGROUND: Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH. METHODS: We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug's water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes' surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug's impact on AML targets. RESULTS: We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells. CONCLUSION: The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy.

Can the Sterilization Protocol Be Improved to Enhance the Healing of Allograft Tendons? An In Vivo Study in Rabbit Tendons.

BACKGROUND: Peracetic acid and irradiation are common sterilization methods for allograft tendons; however, under some conditions, both methods adversely affect the fiber arrangement and ultimate load of the tendon. An in vitro study showed that low-dose peracetic acid combined with irradiation may be less detrimental to allograft tendon structure and properties, possibly because the breakdown of peracetic acid can lead to an enlargement of the interstitial spaces and an increase in porosity. QUESTIONS/PURPOSES: Using a rabbit Achilles tendon model, we asked: What is the effect of peracetic acid-ethanol combined irradiation on (1) the histopathology and fiber diameter of the allograft tendon, (2) tensile creep and load-to-failure biomechanical properties of allograft tendons, and (3) healing of the treated tendon in vivo compared with fresh-frozen allograft and peracetic acid-ethanol sterilization at 4 and 8 weeks? METHODS: The Achilles tendons used in this study were sourced from euthanized 10-week-old male New Zealand White rabbits previously used for ophthalmic experiments. All allografts were divided into three groups: fresh-frozen group (control group, n = 20), peracetic acid-ethanol sterilization group (n =20), and peracetic acid-ethanol combined irradiation group (n = 20). The sterilization protocols were performed per a predetermined plan. In the peracetic acid-ethanol sterilization group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (1% peracetic acid for 30 minutes). In the peracetic acid-ethanol combined irradiation group, the tendon tissues were covered with the peracetic acid-ethanol sterilization solution (0.2% peracetic acid for 30 minutes) and were subjected to 15 kGy gamma irradiation. Thirty 10-week-old male New Zealand White rabbits received bilateral Achilles tendon allografts surgically. Tendon samples from each group were harvested at 4 weeks (n = 30) and 8 weeks (n = 30) postoperatively. For each timepoint, eight tissues were used for histologic staining and electron microscopy, 15 tissues were used for biomechanical testing, and seven tissues were used for hydroxyproline assay and quantitative polymerase chain reaction. Histopathology was determined qualitatively by hematoxylin and eosin and Masson staining, while fiber diameter was measured quantitatively by transmission electron microscopy. Biomechanical properties were measured using cyclic loading tests and load-to-failure tests. The healing outcome was quantitatively judged through healing-related genes and proteins. RESULTS: At 4 weeks and 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group visually demonstrated the best continuity and minimal peripheral adhesions. Histologic staining showed that tendon fibers in the peracetic acid-ethanol combined irradiation group maintained consistent alignment without notable disruptions or discontinuities, and there was a qualitatively observed increase in the number of infiltrating cells compared with the control group at the 4-week timepoint (444 ± 49 /mm 2 versus 256 ± 43 /mm 2 , mean difference 188 /mm 2 [95% confidence interval 96 to 281]; p < 0.001). At 8 weeks postoperatively, the tendon fiber diameter in the peracetic acid-ethanol combined irradiation groups was similar to that of the control group (0.23 ± 0.04 µm versus 0.21 ± 0.03 µm, mean difference 0.02 µm [95% CI -0.04 to 0.08]; p = 0.56). At 8 weeks postoperatively, the peracetic acid-ethanol combined irradiation group exhibited better properties in terms of both ultimate load (129 ± 15 N versus 89 ± 20 N, mean difference 40 N [95% CI 7 to 73]; p = 0.02) and energy absorption density (17 ± 6 kJ/m 2 versus 8 ± 4 kJ/m 2 , mean difference 8 kJ/m 2 [95% CI 0.7 to 16]; p = 0.004) compared with the control group. Gene expression analysis revealed higher expression levels of COL1A1 (2.1 ± 0.8 versus 1.0 ± 0, mean difference 1.1 [95% CI 0.1 to 2.1]; p = 0.003) and MMP13 (2.0 ± 0.8 versus 1.0 ± 0, mean difference 1.0 [95% CI 0.4 to 1.6]; p = 0.03) in the peracetic acid-ethanol combined irradiation group than in the control group. There was a higher amount of collagen Type I in tendons treated with peracetic acid-ethanol combined irradiation than in the control group (0.36 ± 0.03 versus 0.31 ± 0.04, mean difference 0.05 [95% CI 0.01 to 0.09]; p = 0.02). CONCLUSION: Treatment with peracetic acid-ethanol combined irradiation did not have any discernible adverse effect on the histology, fiber diameter, enzymatic resistance, collagen content, or biomechanical strength of the allograft tendons compared with the control group. Peracetic acid-ethanol combined irradiation treatment had a positive impact on remodeling of the extracellular matrix and realignment of collagen fibers. CLINICAL RELEVANCE: This sterilization method could be helpful to expand the scope and frequency with which allogeneic materials are applied. The long-term healing effect and strength of allograft tendons must be tested before clinical use, and it is necessary to conduct comparative studies on autografts and synthetic materials that are currently widely used clinically.

Adversarial network for multi-input image restoration under strong turbulence.

Turbulence generated by random ups and downs in the refractive index of the atmosphere produces varying degrees of distortion and blurring of images in the camera. Traditional methods ignore the effect of strong turbulence on the image. This paper proposes a deep neural network to enhance image clarity under strong turbulence to handle this problem. This network is divided into two sub-networks, the generator and the discriminator, whose functions are to mitigate the effects of turbulence on the image and to determine the authenticity of the recovered image. After extensive experiments, it is proven that the present network plays a role in mitigating the image degradation problem caused by atmospheric turbulence.

Acacetin Alleviates Cardiac Fibrosis via TGF-ß1/Smad and AKT/mTOR Signal Pathways in Spontaneous Hypertensive Rats.

INTRODUCTION: Attenuating cardiac fibroblasts activation contributes to reducing excessive extracellular matrix deposition and cardiac structural remodeling in hypertensive hearts. Acacetin plays a protective role in doxorubicin-induced cardiomyopathy and ischemia/reperfusion injury. The aim of this study was to investigate the potential molecular mechanisms underlying the protective role of acacetin on hypertension-induced cardiac fibrosis. METHODS: Echocardiography, histopathological methods, and Western blotting techniques were used to evaluate the anti-fibrosis effects in spontaneous hypertensive rat (SHR) which were daily intragastrically administrated with acacetin (10 mg/kg and 20 mg/kg) for 6 weeks. Angiotensin II (Ang II) was used to induce cellular fibrosis in human cardiac fibroblasts (HCFs) in the absence and presence of acacetin treatment for 48 h. RESULTS: Acacetin significantly alleviated hypertension-induced increase in left ventricular (LV) posterior wall thickness and LV mass index in SHR. The expressions of collagen-1, collagen-III, and alpha-smooth muscle actin (α-SMA) were remarkedly decreased after treatment with acacetin (n = 6, p < 0.05). In cultured HCFs, acacetin significantly attenuated Ang II-induced migration and proliferation (n = 6, p < 0.05). Moreover, acacetin substantially inhibited Ang II-induced upregulation of collagen-1 and collagen-III (n = 6, p < 0.05) and downregulated the expression of alpha-SMA in HCFs. Additionally, acacetin decreased the expression of TGF-ß1, p-Smad3/Smad3, and p-AKT and p-mTOR but increased the expression of Smad7 (n = 6, p < 0.05). Further studies found that acacetin inhibited TGF-ß1 agonist SRI and AKT agonist SC79 caused fibrotic effect. CONCLUSION: Acacetin inhibits the hypertension-associated cardiac fibrotic processes through regulating TGF-ß/Smad3, AKT/mTOR signal transduction pathways.

Ten-year trends in surgical management of 1207 congenital scoliosis.

PURPOSE: To report and analyze development trends in the surgical treatment of congenital scoliosis (CS) in a large CS cohort over a 10-year period. METHODS: We retrospectively searched and extracted medical records of CS inpatients receiving posterior instrumented fusion surgery at our institute from January 2010 to December 2019. We analyzed information on demographics and surgical information, including the surgical approach, number of fused segments, use of osteotomy and titanium cage implantation, length of stay, intraoperative blood loss, and rates of complications and readmission. RESULTS: 1207 CS inpatients were included. In the past decade, the proportion of patients younger than 5 years increased from 15.5 to 26.9%. The average number of fused segments decreased from 9.24 to 7.48, and the proportion of patients treated with short-segment fusion increased from 13.4 to 30.3%. The proportion of patients treated with osteotomy and titanium cage implantation increased from 55.65% and 12.03% to 76.5% and 40.22%. The average length of stay and blood loss decreased from 16.5 days and 816.1 ml to 13.5 days and 501.7 ml. The complication and readmission rates also decreased during these ten years. CONCLUSION: During this ten-year period, the surgical treatment of CS at our institute showed trends toward a younger age at fusion, lower number of fused segments, higher rate of osteotomy and titanium cage implantation, reduced blood loss, shorter length of stay and lower rate complications and readmission. These results suggest performing osteotomy combined with titanium cage implantation at an earlier age can achieve fewer fused segments and complications.

Restoration of Mitochondrial Function Is Essential in the Endothelium-Dependent Vasodilation Induced by Acacetin in Hypertensive Rats.

Mitochondrial dysfunction in the endothelium contributes to the progression of hypertension and plays an obligatory role in modulating vascular tone. Acacetin is a natural flavonoid compound that has been shown to possess multiple beneficial effects, including vasodilatation. However, whether acacetin could improve endothelial function in hypertension by protecting against mitochondria-dependent apoptosis remains to be determined. The mean arterial pressure (MAP) in Wistar Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) administered with acacetin intraperitoneally for 2 h or intragastrically for six weeks were examined. The endothelial injury was evaluated by immunofluorescent staining and a transmission electron microscope (TEM). Vascular tension measurement was performed to assess the protective effect of acacetin on mesenteric arteries. Endothelial injury in the pathogenesis of SHR was modeled in HUVECs treated with Angiotensin II (Ang II). Mitochondria-dependent apoptosis, the opening of Mitochondrial Permeability Transition Pore (mPTP) and mitochondrial dynamics proteins were determined by fluorescence activated cell sorting (FACS), immunofluorescence staining and western blot. Acacetin administered intraperitoneally greatly reduced MAP in SHR by mediating a more pronounced endothelium-dependent dilatation in mesenteric arteries, and the vascular dilatation was reduced remarkably by NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis. While acacetin administered intragastrically for six weeks had no apparent effect on MAP, it improved the endothelium-dependent dilatation in SHR by activating the AKT/eNOS pathway and protecting against the abnormalities of endothelium and mitochondria. Furthermore, acacetin remarkably inhibited Ang II induced apoptosis by inhibiting the increased expression of Cyclophilin D (CypD), promoted the opening of mPTP, ROS generation, ATP loss and disturbance of dynamin-related protein 1 (DRP1)/optic atrophy1 (OPA1) dynamics in HUVECs. This study suggests that acacetin protected against endothelial dysfunction in hypertension by activating the AKT/eNOS pathway and modulating mitochondrial function by targeting mPTP and DRP1/OPA1-dependent dynamics.

Environmental titanium exposure and reproductive health: Risk of low birth weight associated with maternal titanium exposure from a nested case-control study in northern China.

Titanium (Ti) is commonly used in additives in the form of titanium dioxide (TiO2). However, our understanding of the effect of Ti on reproductive health remains limited. This nested case-control study, performed in a Ti mining exposure field, investigated the association between maternal blood Ti concentration and the risk of low birth weight (LBW), as well as the potential biological mechanism. A total of 45 women who delivered LBW infants (cases) and 352 women with normal birth weight infants (controls) were included. We collected maternal peripheral blood samples in the first or early second trimester to measure Ti concentration in serum (Tisr) and blood cells (Tibc), as well as inflammatory, lipid, and oxidative stress biomarkers thereof. The demographic characteristics of the women included in the study were also obtained. The results showed that the median total blood Ti concentration (Titb) in the case group was significantly higher than that in the control group (134 vs. 129 ng/mL, P = 0.039). A higher Titb level was associated with a greater risk of LBW [odds ratio = 2.62; 95% confidence interval (CI): 1.16-5.90], but no such association was observed for Tisr or Tibc after adjusting for potential confounders. The serum lipid biomarkers TC, TG, and total lipids (TL) were all negatively associated with Tisr and Titb. Serum 8-OHdG was positively associated with Tibc. We concluded that a high Titb during early pregnancy may increase the risk of LBW. Lipid metabolism and oxidative stress may play an important role in the adverse health effects associated with Ti exposure. Thus, our results merit more attention to the probable adverse effects of titanium exposure during pregnancy.

Distribution of mercury in serum and blood cells and risk of spontaneous preterm birth: A nested case-control study in China.

The relationship between maternal mercury (Hg) intake and the risk of spontaneous preterm birth (SPB) remains unclear. We conducted a nested case-control study from a prospective cohort in Shanxi Province, China, to explore their associations. In total, 126 pregnant women with SPB (cases) and 348 controls with term delivery were included. We measured the Hg concentrations in their serum (Hgs) and blood cell (Hgc) fractions and calculated the concentration ratio of Hg in serum to Hg in blood cells (Hgs/c). We found that only the Hgs/c in the case group was slightly higher than that in control group. The OR of Hgs/c associated with SPB risk was 1.57 [95%CI: 0.99-2.46] with adjusting confounders. After stratification by sampling time, the association above was only statistically significant in the first trimester. High Hgs/c may increase the risk of SPB in the first trimester among women with relatively low Hg exposure.

Serum kisspeptin levels in polycystic ovary syndrome: A meta-analysis.

AIM: To clarify the association of serum kisspeptin levels in women with polycystic ovary syndrome (PCOS) by meta-analysis. METHODS: Two English databases and two Chinese databases were searched for the relationship between kisspeptin and PCOS published from 2009. After the studies screening according to specific principles, we used STATA 12.0 for meta-analysis. Standardized mean difference (SMD) and its 95% confidence intervals (95% CIs) were used as the effect size and STATA 12.0 software was performed by this meta-analysis. RESULTS: Nine articles were included in the end, with a total of 1282 participants (699 patients and 583 controls). Heterogeneity between studies was statistically significant. Therefore, the random effects model was used to combine the effects. Meta-analysis showed statistically significant differences in serum kisspeptin levels between the PCOS patients and controls (SMD = 0.57, 95% CI [0.32, 0.82]), which indicated that there is a strong association between serum kisspeptin levels and PCOS. The source of high heterogeneity between the inclusion studies (I2  = 73.2%) might be due to the small sample size. The larger variation of kisspeptin concentration might be caused by different diagnosis criteria of PCOS and short half-time period of kisspeptin combined with nonstandard testing process. CONCLUSION: Serum kisspeptin levels in PCOS patients were higher than non-PCOS patients. It is a hint to indicate us that kisspeptin might be an independent biomarker of PCOS patients.

Inhibitory Effects of Dronedarone on Small Conductance Calcium Activated Potassium Channels in Patients with Chronic Atrial Fibrillation: Comparison to Amiodarone.

BACKGROUND Dysfunction of small conductance calcium activated potassium (SK) channels plays a vital role in atrial arrhythmogenesis. Amiodarone and dronedarone are the most effective class III antiarrhythmic drugs. It is unclear whether the antiarrhythmic effect of amiodarone and dronedarone is related to SK channel inhibition. MATERIAL AND METHODS Tissue samples were obtained from the right atria of 46 patients with normal sinus rhythm and 39 patients with chronic atrial fibrillation. Isolated atrial myocytes were obtained by enzymatic dissociation. KCNN2 (SK2) channels were transiently expressed in human embryonic kidney (HEK)-293 cells. SK currents were recorded using whole-cell conventional patch clamp techniques. RESULTS Amiodarone and dronedarone showed a concentration-dependent inhibitory effect on SK currents (IKAS) in atrial myocytes from normal sinus rhythm patients and chronic atrial fibrillation patients. The suppressed efficacy of dronedarone and amiodarone on IKAS was greater in atrial myocytes from chronic atrial fibrillation patients than that from normal sinus rhythm patients. Furthermore, in patients with chronic atrial fibrillation, the IC50 value was 2.42 µM with dronedarone and 8.03 µM with amiodarone. In HEK-293 cells with transiently transfected SK2 channels, both dronedarone and amiodarone had a dose-dependent inhibitory effect on IKAS. The IC50 value was 1.7 µM with dronedarone and 7.2 µM with amiodarone in cells from patients with chronic atrial fibrillation. Compared to amiodarone, dronedarone is more efficacy to inhibit IKAS and could be a potential intervention for patients with chronic atrial fibrillation. CONCLUSIONS Dronedarone provides a great degree of IKAS inhibition in atrial myocytes from chronic atrial fibrillation than amiodarone. IKAS might be a potential target of amiodarone and dronedarone for the management of chronic atrial fibrillation.

Physiological and transcriptomic analyses of mulberry (Morus atropurpurea) response to cadmium stress.

Mulberry (Morus atropurpurea) is an economically important woody tree and has great potential for the remediation of heavy metals. To investigate how cadmium accumulates and its detoxification in mulberry, we assessed the physiological and transcriptomic effects of cadmium contamination and as well as its chemical forms and subcellular distribution. Cadmium significantly inhibited mulberry plant growth and primarily accumulated in mulberry roots. Antioxidant enzymes were induced by cadmium in all tissues of mulberry. Subcellular fractionation analyses of cadmium indicated that the majority was compartmentalized in soluble fraction in roots while it mainly located in cell wall in leaves and stems. The greatest amount of the cadmium was integrated with proteins and pectates in all mulberry tissues. RNA-seq transcriptomic analyses of mulberry roots revealed that various metabolic pathways involved in cadmium stress response such as RNA regulation, hormone metabolism, and response to stress, secondary metabolism, as well as signaling, protein metabolism, transport, and cell-wall metabolism. These results will increase our understanding of the molecular mechanisms of cadmium detoxification in mulberry and provide new insights into engineering woody plants for phytoremediation.

Lower urinary tract symptoms 7 years after the first delivery: Correlation to the mode of delivery.

OBJECTIVE: To investigate the extent of lower urinary tract symptoms (LUTS) during pregnancy and 7 years after birth in primipara and their association with delivery mode history and other factors. METHODS: A longitudinal cohort study was conducted in 12 hospitals representative of the diversity of the seven administrative regions of China. Of 10 098 women recruited at the third trimester, 3862 (38.25%) responded at 1 year, and 1115 (11.04%) responded at 7 years. A modified Chinese Bristol Female Lower Urinary Tract Symptoms questionnaire was administered. No intervention was implemented. RESULTS: Among the participants, 75.4% reported nocturia during gestation, followed by frequency (58.4%), which gradually decreased after delivery. The prevalence of urge urinary incontinence (UUI) increased from 5.7% during pregnancy to 22.8% at 1 year after delivery and 10.2% at 7 years postpartum. The prevalence of stress urinary incontinence (SUI) increased from 29.9% during pregnancy to 46.4% at 1 year postpartum and 23.7% at 7 years after delivery. The odds of storage LUTS and voiding LUTS 7 years after delivery were lower for the cesarean section (CS) group than for the vaginal delivery (VD) group (OR = 0.49, 95%CI, 0.36-0.68; OR = 0.25, 95%CI, 0.09-0.70). The most frequent moderately to severely bothersome LUTS after VD was SUI (19.18%), while that for CS was UUI (19.18%). CONCLUSION: The incidence of storage LUTS was higher than that of voiding LUTS both during pregnancy and postpartum. The most frequently reported LUTS during pregnancy were nocturia and frequency, while the most frequent LUTS after delivery were urgency and SUI. CS was associated with a decreased prevalence of both storage and voiding LUTS after delivery.

An epidemiologic study of pelvic organ prolapse in rural Chinese women: a population-based sample in China.

INTRODUCTION AND HYPOTHESIS: We aimed to investigate the prevalence and risk factors of symptomatic pelvic organ prolapse (POP) in rural China. METHODS: A cross-sectional study of POP was conducted in rural China from February 2014 to March 2016. In total, 25,864 rural women were recruited. All were asked to complete a questionnaire that included questions about their age, job, parity, diseases, and so on. Symptomatic POP was assessed using Pelvic Organ Prolapse Quantification (POP-Q) system staging and validation questionnaires. Multivariate logistic regression was used to assess the factors associated with symptomatic POP. RESULTS: The prevalence of symptomatic POP was 9.10%. There was a consistent trend toward an increasing prevalence of POP with increasing age, ranging from 2.53 to 13.40% (P < 0.0001). Women aged 50-59 years [adjusted odds ratio (AOR) 1.86, 95% confidence interval (CI) 1.46-2.37] were more likely to have POP than women aged 20-29 years. POP was positively associated with giving birth to more than three children (AOR 2.18, 95% CI 1.88-2.43). Cesarean section was a significant protective factor (AOR = 0.34, 95% CI 0.33-0.49) compared with vaginal delivery. Multivariate logistic regression analysis showed that obesity, constipation, smoking, coughing, gynecological diseases, and other physical diseases were also associated with POP. CONCLUSIONS: Symptomatic POP affects a substantial proportion of women in rural China. Older age, multiparity, vaginal delivery, obesity, and many chronic conditions significantly increased the odds of developing symptomatic POP. Additional healthcare campaigns are needed to educate women in rural areas about POP.

Metal distribution and biological diversity of crusts in paddy fields polluted with different levels of cadmium.

The paddy-crusts (PCs) play an important pole in the transformation and transfer of heavy metal in paddy. Different PCs were collected from paddy fields whose soils contained cadmium (Cd) at four concentration levels (0.61, 0.71, 1.53, and 7.08 mg/kg) in Hunan Province, China P.R. at Sep 2017. This metal's distribution among and biological community structures of PCs were both measured. Our results indicated that PCs were able to accumulate Cd from irrigation water and soil. With greater Cd levels in paddy fields, the weak EPS-binding Cd fraction decreased whereas the non-EDTA-exchangeable Cd fraction increased. The sorbed Cd fraction was initially enhanced at low-to mid-level Cd concentrations, but then gradually declined. Biomineralization was shown to function as the dominant Cd accumulation mechanism in non-EDTA-exchangeable fractions. The biological diversity of soil microbes decreased with more Cd in soil, and the Proteobacteria, Bacteroidetes, and Cyanobacteria were the dominant phyla in all the sampled PCs. Canonical correspondence analysis (CCA) between the composition of microbial communities and soil chemical variables in the PCs clustered all samples based on the Cd-contaminated level, and demonstrated that Cd, Mn, and Fe all significantly influenced the microbial communities. In particular, the Alphaproteobacteria and Chloroplast classes of bacteria may play a significant role in Cd accumulation via the bio-mineralization process. Taken together, our results provide basic empirical information to better understand the heavy metal speciation transformation mechanisms of PCs upon Cd-contaminated paddy fields.

[Novel mutations of GLB1 gene identified in a Chinese pedigree affected with GM1 gangliosidosis].

OBJECTIVE: To explore the genetic cause for a child with growth retardation by next generation sequencing (NGS). METHODS: Clinical data of the patient was collected. Peripheral venous blood samples were taken from the neonate and his parents. Targeted capturing and NGS were carried out to detect mutations of genes associated with inborn errors of metabolism. Suspected mutations were validated by Sanger sequencing. RESULTS: The 15-month-old female patient was admitted to hospital for growth retardation for 4 months. Hypomyelination was found upon cranium MRI. Genetic testing revealed two novel insertional mutations in the GLB1 gene in the patient, namely c.2006-2007insT and c.475-476 insGGTCC. CONCLUSION: The c.2006-2007insT and c.475-476 insGGTCC mutations of the GLB1 gene probably underlie the GM1 gangliosidosis resulting in the growth retardation in the child.

Vindel: a simple pipeline for checking indel redundancy.

BACKGROUND: With the advance of next generation sequencing (NGS) technologies, a large number of insertion and deletion (indel) variants have been identified in human populations. Despite much research into variant calling, it has been found that a non-negligible proportion of the identified indel variants might be false positives due to sequencing errors, artifacts caused by ambiguous alignments, and annotation errors. RESULTS: In this paper, we examine indel redundancy in dbSNP, one of the central databases for indel variants, and develop a standalone computational pipeline, dubbed Vindel, to detect redundant indels. The pipeline first applies indel position information to form candidate redundant groups, then performs indel mutations to the reference genome to generate corresponding indel variant substrings. Finally the indel variant substrings in the same candidate redundant groups are compared in a pairwise fashion to identify redundant indels. We applied our pipeline to check for redundancy in the human indels in dbSNP. Our pipeline identified approximately 8% redundancy in insertion type indels, 12% in deletion type indels, and overall 10% for insertions and deletions combined. These numbers are largely consistent across all human autosomes. We also investigated indel size distribution and adjacent indel distance distribution for a better understanding of the mechanisms generating indel variants. CONCLUSIONS: Vindel, a simple yet effective computational pipeline, can be used to check whether a set of indels are redundant with respect to those already in the database of interest such as NCBI's dbSNP. Of the approximately 5.9 million indels we examined, nearly 0.6 million are redundant, revealing a serious limitation in the current indel annotation. Statistics results prove the consistency of the pipeline on indel redundancy detection for all 22 chromosomes. Apart from the standalone Vindel pipeline, the indel redundancy check algorithm is also implemented in the web server http://bioinformatics.cs.vt.edu/zhanglab/indelRedundant.php .

An anti-occlusion optimization algorithm for multiple pedestrian tracking.

Frequent occlusion of tracking targets leads to poor performance of tracking algorithms. A common practice in multi-target tracking algorithms is to re-identify the occluded tracking targets, which increases the number of identity switching occurrences. This paper focuses on online multi-object tracking and designs an anti-occlusion, robust association strategy, and feature extraction model. Specifically, the least squares algorithm and the Kalman filter are used to predict the trajectory of the tracking target, while the two-way self-attention mechanism is employed to extract the features of the tracking target, as well as positive and negative samples. After the tracking target is occluded, the association strategy is used to assign the identity information from before the occlusion. The experimental results demonstrate that the algorithm proposed in this paper has achieved excellent tracking performance on the MOT dataset.

Finite-size scaling of the high-dimensional Ising model in the loop representation.

Besides its original spin representation, the Ising model is known to have the Fortuin-Kasteleyn (FK) bond and loop representations, of which the former was recently shown to exhibit two upper critical dimensions (d_{c}=4,d_{p}=6). Using a lifted worm algorithm, we determine the critical coupling as K_{c}=0.07770891(4) for d=7, which significantly improves over the previous results, and then study critical geometric properties of the loop Ising clusters on tori for spatial dimensions d=5 to 7. We show that as the spin representation, the loop Ising model has only one upper critical dimension at d_{c}=4. However, sophisticated finite-size scaling (FSS) behaviors, such as two length scales, two configuration sectors, and two scaling windows, still exist as the interplay effect of the Gaussian fixed point and complete-graph asymptotics. Moreover, using the loop-cluster algorithm, we provide an intuitive understanding of the emergence of the percolation-like upper critical dimension d_{p}=6 in the FK-Ising model. As a consequence, a unified physical picture is established for the FSS behaviors in all three representations of the Ising model above d_{c}=4.