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Abstract We analyzed genomic data from the prostate cancer of African- and European American men to identify differences contributing to racial disparity of outcome. We also performed FISH-based studies of Chromodomain helicase DNA-binding protein 1 (CHD1) loss on prostate cancer tissue microarrays. We created CHD1-deficient prostate cancer cell lines for genomic, drug sensitivity and functional homologous recombination (HR) activity analysis. Subclonal deletion of CHD1 was nearly three times as frequent in prostate tumors of African American than in European American men and it associates with rapid disease progression. CHD1 deletion was not associated with HR deficiency associated mutational signatures or HR deficiency as detected by RAD51 foci formation. This was consistent with the moderate increase of olaparib and talazoparib sensitivity with several CHD1 deficient cell lines showing talazoparib sensitivity in the clinically relevant concentration range. CHD1 loss may contribute to worse disease outcome in African American men.

Summary: The kidney is a vital organ responsible for water and sodium metabolism, while the primary function of amiloride is to promote the excretion of water and sodium. We investigated amiloride enhanced the sunitinib sensitivity in RCC. We found both sunitinib and amiloride displayed cytotoxicity and exerted the synergy effect in RCC cells in vivo and in vitro arrays. Protein expression profiles were screened via MS/TMT, revealing that FN3K was upregulated in the sunitinib group, and rescued in amiloride and the combination administration. Exogenous FN3K could promote proliferation, invasion and metastasis and decrease the sensitivity of Caki-1 cells to sunitinib, also, exogenous FN3K up-regulated VEGFR2 expression and activated AKT/mTOR signal pathway. More FN3K and VEGFR2 accumulated in R-Caki-1 cells and rescued by amiloride treatment. Co-IP and IF confirmed the interaction between FN3K and VEGFR2. In conclusion, FN3K depletion mediated VEGFR2 disruption promotes amiloride synergized the anti-RCC activity of sunitinib.

Background: We sought to establish a prospective hospital-based cohort, featuring detailed multidimensional data of trauma patients with active follow-ups, which can be a reliable data source for all studies focusing on the effects or underlying mechanistic pathways of environmental and biological factors on multiple interested trauma-related outcomes, particularly the incidence and trajectory of trauma-related psychopathology, in a Chinese population. Methods: The China Severe Trauma Cohort (CSTC) enrolled all traumatized individuals aged 12 to 80 years admitted to the Trauma Center of West China Hospital between March 1st, 2020 and July 8th, 2022. The bio-sample and detailed questionnaire data were collected at recruitment, and phone/internet follow-ups were scheduled at 1, 3, 6, and 12 months after the baseline. Long-term health outcomes are planned to be obtained from administrative databases through data linkage. Results: A total of 2,500 trauma patients were enrolled (response rate = 87.1%) with an average age of 46.01 years, and most of the participants were males (62.6%). The proportions of participants with blood and fecal sample collected at baseline were 93.8% and 66.3%, respectively. As of August 31st, 2022, the follow-up rate was 90.0%, 77.0%, 76.5%, and 89.0% for 1-, 3-, 6-, and 12-month follow-ups, respectively. Fall/wrench (47.6%) and traffic accident (26.2%) were the top causes of current trauma. The most common psychopathology at recruitment was sleep disturbance (39.4%), followed by depression (22.6%), anxiety (18.2%), and acute stress reaction (7.8%), all of which showed recovering trajectories during the follow-up period, particularly the first 3 months after baseline. Conclusion: CSTC provides a platform with multidimensional data to study both short-term and long-term trauma-related health consequences, prompting early identification and intervention for individuals with high risk of health decline after trauma exposures.

Summary: Electrocatalytic generation of H2O2 via the 2-electron pathway of oxygen reduction reaction (2e-ORR) is an attractive technology compared to the anthraquinone process due to convenience and environmental friendliness. However, catalysts with excellent selectivity and high activity for 2e-ORR are necessary for practical applications. Reported here is a catalyst comprising boron-doped porous carbon hollow spheres (B-PCHSs) prepared using the hard template method coupled with borate transesterification. In an alkali electrolyte, the selectivity of B-PCHS for 2e-ORR above 90% in range of 0.4–0.7 VRHE and an onset potential of 0.833 V was obtained. Meanwhile, the generation rate of H2O2 reached 902.48 mmol h−1 gcat−1 at 0.4 VRHE under 59.13 mA cm−2 in batch electrolysis. The excellent catalytic selectivity of B-PCHS for 2e-ORR originates from the boron element, and the catalytic activity of B-PCHS for H2O2 generation is contributed to the morphology of porous hollow spheres, which facilitates mass transfer processes.

Abstract Early identification of a patient with a high risk of blood transfusion during brain tumor resection surgery is difficult but critical for implementing preoperative blood-saving strategies. This study aims to develop and validate a machine learning prediction tool for intraoperative blood transfusion in brain tumor resection surgery. A total of 541 patients who underwent brain tumor resection surgery in our hospital from January 2019 to December 2021 were retrospectively enrolled in this study. We incorporated demographics, preoperative comorbidities, and laboratory risk factors. Features were selected using the least absolute shrinkage and selection operator (LASSO). Eight machine learning algorithms were benchmarked to identify the best model to predict intraoperative blood transfusion. The prediction tool was established based on the best algorithm and evaluated with discriminative ability. The data were randomly split into training and test groups at a ratio of 7:3. LASSO identified seven preoperative relevant factors in the training group: hemoglobin, diameter, prothrombin time, white blood cell count (WBC), age, physical status of the American Society of Anesthesiologists (ASA) classification, and heart function. Logistic regression, linear discriminant analysis, supporter vector machine, and ranger all performed better in the eight machine learning algorithms with classification errors of 0.185, 0.193, 0.199, and 0.196, respectively. A nomogram was then established, and the model showed a better discrimination ability [0.817, 95% CI (0.739, 0.895)] than hemoglobin [0.663, 95% CI (0.557, 0.770)] alone in the test group (P = 0.000). Hemoglobin, diameter, prothrombin time, WBC, age, ASA status, and heart function are risk factors of intraoperative blood transfusion in brain tumor resection surgery. The prediction tool established using the logistic regression algorithm showed a good discriminative ability than hemoglobin alone for predicting intraoperative blood transfusion in brain tumor resection surgery.

Abstract Background The quality of life (QoL) of elderly patients with bone trauma is significantly decreased and is affected by many complex factors. This study aims to conduct a half-year follow-up survey to clarify QoL and its influencing factors in elderly patients with bone trauma in order to provide targeted care measures for elderly patients with bone trauma. Methods This was a longitudinal observational study. We used the 36-Item Short Form Health Survey (SF-36) to investigate and evaluate the QoL of 100 patients with bone trauma at the time of hospital discharge and 1 month, 3 months, and 6 months after discharge. Our previous study confirmed that the SF-36 had higher reliability and validity for evaluating the QoL of elderly patients with bone trauma. At the same time, we also investigated the age, gender, location of bone trauma, and destination after discharge of those patients. Those factors that might affect the QoL of elderly patients with bone trauma were identified by univariate and multivariate analyses. Results The total physiological function, role-physical, bodily pain, vitality, social functioning, role-emotional, and mental health scores of elderly patients with bone trauma gradually increased from the time of discharge to 1 month, 3 months, and 6 months after discharge, and there were significant differences (p

Site specific biotinylation of AviTagged recombinant proteins using BirA enzyme is a widely used protein labeling technology. However, due to the incomplete biotinylation reactions and the lack of a purification method specific for the biotinylated proteins, it is challenging to purify the biotinylated sample when mixed with the non-biotinylated byproduct. Here, we have developed a monoclonal antibody that specifically recognizes the non-biotinylated AviTag but not the biotinylated sequence. After a ten-minute incubation with the resin that is conjugated with the antibody, the non-biotinylated AviTagged protein is trapped on the resin while the fully biotinylated material freely passes through. Therefore, our AviTrap (anti-AviTag antibody conjugated resin) provides an efficient solution for enriching biotinylated AviTagged proteins via a simple one-step purification.

Hydrogels as semi-solid materials with highly tunable mechanical properties are promising materials in numerous fields. The emergence of self-healing hydrogels, with the ability to recover their original structure post-fracture, has further expanded their applications in flexible devices, wound healing, and implant materials. Biopolymers have the advantages of biocompatibility, biodegradability, and environmental sustainability, making the self-healing hydrogels from biopolymers more promising materials in biomedical applications. In this paper, we started from the dynamic bonds that used to realize the self-healing properties of biopolymer-based hydrogels, and discussed their advantages and disadvantages. The construction mechanisms, self-healing properties of the hydrogels from different biopolymers were then introduced separately. We also reviewed the their potential applications, and discussed their challenges and prospects.

Abstract Background The factors that maintain phenotypic and genetic variation within a population have received long-term attention in evolutionary biology. Here the genetic basis and evolution of the geographically widespread variation in twig trichome color (from red to white) in a shrub Melastoma normale was investigated using Pool-seq and evolutionary analyses. Results The results show that the twig trichome coloration is under selection in different light environments and that a 6-kb region containing an R2R3 MYB transcription factor gene is the major region of divergence between the extreme red and white morphs. This gene has two highly divergent groups of alleles, one of which likely originated from introgression from another species in this genus and has risen to high frequency (> 0.6) within each of the three populations under investigation. In contrast, polymorphisms in other regions of the genome show no sign of differentiation between the two morphs, suggesting that genomic patterns of diversity have been shaped by homogenizing gene flow. Population genetics analysis reveals signals of balancing selection acting on this gene, and it is suggested that spatially varying selection is the most likely mechanism of balancing selection in this case. Conclusions This study demonstrate that polymorphisms on a single transcription factor gene largely confer the twig trichome color variation in M. normale, while also explaining how adaptive divergence can occur and be maintained in the face of gene flow.

Nowadays, due to the cleanliness and high efficiency of grid-connected new energy, it has become more and more popular in the market. However, there are still some problems in grid-connected power control and cannot be well supervised. Therefore, this paper studies a new energy grid-connected power control method based on predictive regulation performance and embedded systems, aiming to control new energy grid-connected power through predictive regulation performance and embedded systems. In this paper, the predictive regulation performance and energy conversion rate of the embedded system new energy grid connection are tested. In the experiment, the energy conversion rate was between 60% and 70%, while the traditional new energy grid connection rate was between 40% and 60%. The maximum power generation efficiency of new energy grid-connected with predictive regulation performance and embedded systems was 83%, while the maximum power generation efficiency of traditional new energy grid-connected was 68%. It can be seen from these experimental results that predictive regulation performance and embedded systems have good effects on new energy grid-connected power control.

A convenient method for methane (CH4) direct conversion to methanol (CH3OH) is of great significance to use methane-rich resources, especially clathrates and stranded shale gas resources located in remote regions. Theoretically, the activation of CH4 and the selectivity to the CH3OH product are challenging due to the extreme stability of CH4 and relatively high reactivity of CH3OH. The state-of-the-art ‘methane reforming - methanol synthesis’ process adopts a two-step strategy to avoid the further reaction of CH3OH under the harsh conditions required for CH4 activation. In the electrochemical field, researchers are trying to develop conversion pathways under mild conditions. They have found suitable catalysts to activate the C–H bonds in methane with the help of external charge and have designed the electrode reactions to continuously generate certain active oxygen species. These active oxygen species attack the activated methane and convert it to CH3OH, with the benefit of avoiding over-oxidation of CH3OH, and thus obtain a high conversion efficiency of CH4 to CH3OH. This mini-review focuses on the advantages and challenges of electrochemical conversion of CH4 to CH3OH, especially the strategies for supplying electro-generated active oxygen species in-situ to react with the activated methane.

Abstract Background There is substantial variability in prostate cancer (PCa) mortality rates across Caucasian American (CA), African American (AA), Asian, and Hispanic men; however, these estimates are unable to disentangle race or ethnicity from confounding factors. The current study explores survival differences in long‐term PCa outcomes between self‐reported AA and CA men, and examines clinicopathologic features across self‐reported CA, AA, Asian, and Hispanic men. Methods This retrospective cohort study utilized the Center for Prostate Disease Research (CPDR) Multi‐center National Database from 1990 to 2017. Subjects were consented at military treatment facilities nationwide. AA, CA, Asian, or Hispanic men who underwent radical prostatectomy (RP) for localized PCa within the first year of diagnosis were included in the analyses. Time from RP to biochemical recurrence (BCR), BCR to metastasis, and metastasis to overall death were evaluated using Kaplan–Meier unadjusted estimation curves and adjusted Cox proportional hazards regression. Results This study included 7067 men, of whom 5155 (73%) were CA, 1468 (21%) were AA, 237 (3%) were Asian, and 207 (3%) were Hispanic. AA men had a significantly decreased time from RP to BCR compared to CA men (HR = 1.25, 95% CI = 1.06–1.48, p = 0.01); however, no difference was observed between AA and CA men for a time from BCR to metastasis (HR = 0.73, 95% CI = 0.39–1.33, p = 0.302) and time from metastasis to overall death (HR = 0.67, 95% CI = 0.36–1.26, p = 0.213). Conclusions In an equal access health care setting, AA men had a shorter survival time from RP to BCR, but comparable survival time from BCR to metastasis and metastasis to overall death.

Abstract Background Prognostic indicators, treatments, and survival estimates vary by cancer type. Therefore, disease-specific models are needed to estimate patient survival. Our primary aim was to develop models to estimate survival duration after treatment for skeletal-related events (SREs) (symptomatic bone metastasis, including impending or actual pathologic fractures) in men with metastatic bone disease due to prostate cancer. Such disease-specific models could be added to the PATHFx clinical-decision support tool, which is available worldwide, free of charge. Our secondary aim was to determine disease-specific factors that should be included in an international cancer registry. Methods We analyzed records of 438 men with metastatic prostate cancer who sustained SREs that required treatment with radiotherapy or surgery from 1989–2017. We developed and validated 6 models for 1-, 2-, 3-, 4-, 5-, and 10-year survival after treatment. Model performance was evaluated using calibration analysis, Brier scores, area under the receiver operator characteristic curve (AUC), and decision curve analysis to determine the models’ clinical utility. We characterized the magnitude and direction of model features. Results The models exhibited acceptable calibration, accuracy (Brier scores 0.73). Decision curve analysis determined that all 6 models were suitable for clinical use. The order of feature importance was distinct for each model. In all models, 3 factors were positively associated with survival duration: younger age at metastasis diagnosis, proximal prostate-specific antigen (PSA)

DNA damage repair genes have been linked with increased aggressiveness of prostate cancer, however, the extent of mutation of these genes has not been analyzed within a cohort of African American patients. Here, the authors identify increased mutation rates in specific DNA repair genes, compared with prostate cancer patients with European Ancestry.

Abstract TP53 is one of the most frequently altered genes in prostate cancer. The precise assessment of its focal alterations in primary tumors by immunohistochemistry (IHC) has significantly enhanced its prognosis. p53 protein expression and lymphovascular invasion (LVI) were evaluated for predicting metastatic progression by IHC staining of representative whole-mounted prostate sections from a cohort of 189 radical prostatectomy patients with up to 20 years of clinical follow-up. Kaplan–Meier survival curves were used to examine time to distant metastasis (DM) as a function of p53 expression and LVI status. TP53 targeted sequencing was performed in ten tumors with the highest expression of p53 staining. Nearly half (49.8%) of prostate tumors examined showed focal p53 expression while 26.6% showed evidence of LVI. p53(+) tumors had higher pathologic T stage, Grade Group, Nuclear Grade, and more frequent LVI. p53 expression of > 5% and LVI, individually and jointly, are associated with poorer DM-free survival. TP53 mutations were detected in seven of ten tumors sequenced. Four tumors with the highest p53 expression harbored likely pathogenic or pathogenic mutations. High levels of p53 expression suggest the likelihood of pathogenic TP53 alterations and, together with LVI status, could enhance early prognostication of prostate cancer progression.

To improve the water absorbency and water-retention rate of superabsorbent materials, a porous calcium carbonate composite superabsorbent polymer (PCC/PAA) was prepared by copolymerization of acrylic acid and porous calcium carbonate prepared from ground calcium carbonate. The results showed that the binding energies of C–O and C=O in the O 1s profile of PCC/PAA had 0.2 eV and 0.1–0.7 eV redshifts, respectively, and the bonding of –COO− groups on the surface of the porous calcium carbonate led to an increase in the binding energy of O 1s. Furthermore, the porous calcium carbonate chelates with the –COO− group in acrylic acid through the surface Ca2+ site to form multidirectional crosslinking points, which would increase the flexibility of the crosslinking network and promote the formation of pores inside the PCC/PAA to improve the water storage space. The water absorbency of PCC/PAA with 2 wt% porous calcium carbonate in deionized water and 0.9 wt% NaCl water solution increased from 540 g/g and 60 g/g to 935 g/g and 80 g/g, respectively. In addition, since the chemical crosslinker N,N′-methylene bisacrylamide is used in the polymerization process of PCC/PAA, N,N′-methylene bisacrylamide and porous calcium carbonate enhance the stability of the PCC/PAA crosslinking network by double-crosslinking with a polyacrylic acid chain, resulting in the crosslinking network of PCC/PAA not being destroyed after water absorption saturation. Therefore, PCC/PAA with 2 wt% porous calcium carbonate improved the water-retention rate by 244% after 5 h at 60 °C, and the compressive strength was approximately five-times that of the superabsorbent without porous calcium carbonate.

While antibody-dependent cellular phagocytosis mediated by activating Fcγ receptor is a key mechanism underlying many antibody drugs, their full therapeutic activities can be restricted by the inhibitory Fcγ receptor IIB (FcγRIIB). Here, we describe a bispecific antibody approach that harnesses phagocytic receptor CLEC5A (C-type Lectin Domain Containing 5A) to drive Fcγ receptor-independent phagocytosis, potentially circumventing the negative impact of FcγRIIB. First, we established the effectiveness of such an approach by constructing bispecific antibodies that simultaneously target CLEC5A and live B cells. Furthermore, we demonstrated its in vivo application for regulatory T cell depletion and subsequent tumor regression.

The mammalian testis adopts an immune privileged environment to protect male germ cells from adverse autoimmune reaction. The testicular immune privileged status can be also hijacked by various microbial pathogens as a sanctuary to escape systemic immune surveillance. In particular, several viruses have a tropism for the testis. To overcome the immune privileged status and mount an effective local defense against invading viruses, testicular cells are well equipped with innate antiviral machinery. However, several viruses may persist an elongated duration in the testis and disrupt the local immune homeostasis, thereby impairing testicular functions and male fertility. Moreover, the viruses in the testis, as well as other organs of the male reproductive system, can shed to the semen, thus allowing sexual transmission to partners. Viral infection in the testis, which can impair male fertility and lead to sexual transmission, is a serious concern in research on known and on new emerging viruses. To provide references for our scientific peers, this article reviews research achievements and suggests future research focuses in the field.

Abstract Background The relationship between race, prostate tumor location, and BCR‐free survival is inconclusive. This study examined the independent and joint roles of patient race and tumor location on biochemical recurrence‐free (BCR) survival. Methods A retrospective cohort study was conducted among men with newly diagnosed, biopsy‐confirmed, NCCN‐defined low risk CaP who underwent radical prostatectomy (RP) at the Walter Reed National Military Medical Center from 1996 to 2008. BCR‐free survival was modeled using Kaplan‐Meier estimation curves and multivariable Cox proportional hazards (PH) analyses. Results There were 539 eligible patients with low‐risk CaP (25% African American, AA; 75% Caucasian American, CA). Median age at CaP diagnosis and post‐RP follow‐up time was 59.2 and 8.1 years, respectively. Kaplan‐Meier analyses showed no significant association between race (P = .52) or predominant tumor location (P = .98) on BCR‐free survival. In Cox PH multivariable analysis, neither race (HR = 1.18; 95% CI = 0.68‐2.02; P = .56) nor predominant tumor location (HR = 1.13; 95% CI = 0.59‐2.15; P = .71) was an independent predictor of BCR‐free survival. Conclusions Neither race nor predominant tumor location was associated with adverse oncologic outcome.

Abstract Background Predicting the clinical course of prostate cancer is challenging due to the wide biological spectrum of the disease. The objective of our study was to identify prostate cancer prognostic markers in patients ‘sera using a multi-omics discovery platform. Methods Pre-surgical serum samples collected from a longitudinal, racially diverse, prostate cancer patient cohort (N = 382) were examined. Linear Regression and Bayesian computational approaches integrated with multi-omics, were used to select markers to predict biochemical recurrence (BCR). BCR-free survival was modeled using unadjusted Kaplan–Meier estimation curves and multivariable Cox proportional hazards analysis, adjusted for key pathologic variables. Receiver operating characteristic (ROC) curve statistics were used to examine the predictive value of markers in discriminating BCR events from non-events. The findings were further validated by creating a training set (N = 267) and testing set (N = 115) from the cohort. Results Among 382 patients, 72 (19%) experienced a BCR event in a median follow-up time of 6.9 years. Two proteins—Tenascin C (TNC) and Apolipoprotein A1V (Apo-AIV), one metabolite—1-Methyladenosine (1-MA) and one phospholipid molecular species phosphatidic acid (PA) 18:0-22:0 showed a cumulative predictive performance of AUC = 0.78 [OR (95% CI) = 6.56 (2.98–14.40), P 80%) for BCR. The combination of pTstage and Gleason score with the analytes, further increased the sensitivity [AUC = 0.89, 95% (CI) = 4.45–32.05, P

Purpose. There remains a lack of consensus among experts regarding the optimal therapeutic approach for Mantle cell lymphoma (MCL) after failure of covalent Bruton Tyrosine Kinase inhibitor (cBTKi)-based therapy. This study was designed to examine patient characteristics, current treatment patterns, and clinical outcomes using a real-world database to evaluate how MCL is currently managed post-cBTKi therapy in the U.S. Methods. A large, deidentified U.S. electronic medical record (EMR) oncology database (ConcertAI) with data from January 2011 to July 2021 was utilized for this study. Eligible patients were adults with MCL who had received at least one cBTKi. Descriptive statistics were used to evaluate patient characteristics and treatment patterns. Time-to-event real-world outcomes of duration of therapy, time to next treatment discontinuation, and overall survival was evaluated using the Kaplan–Meier method. Results. A total of 946 patients met eligibility criteria. Of these, 739 (78.1%) discontinued cBTKi treatment before the end of the follow-up period, while the remaining 207 (21.9%) were still receiving cBTKi therapy at the end of the follow-up period. Among those who had discontinued the cBTKi, 352 (47.6%, 352/739) received at least one subsequent (post-cBTKi) treatment. The median duration of the immediate post-cBTKi therapy was 2.6 months (n = 352). Among the 739 patients who discontinued cBTKi treatment, the median time from cBTKi discontinuation to next treatment discontinuation or death was 3.9 months and the median overall survival was 10.3 months. Conclusions. This study demonstrates the poor outcomes experienced by patients after cBTKi therapy. There is an urgent need for safe and effective treatments for patients with recurrent or progressive MCL.

In studies of vestibulo-ocular reflex (VOR), the horizontal VOR circuit is much clearer than vertical-torsional VOR. The circuit and mechanism of gravity-related vertical-torsional VOR is probably weak. "Somatosensory vestibular interaction" is a known extra source to facilitate VOR, and cervico-ocular reflex is a representative for torsional VOR compensation. Whereas, how the cervical afferents finally reach the oculomotor system is less documented. Actually, when the head tilts, which generates cervico-ocular reflex, not only the neck muscle is activated, but also the jaw muscle is stretched by gravity dragged mandible and/or tissue-muscle connection between the mandible and clavicle. We have previously identified a projection from the jaw muscle afferent mesencephalic trigeminal nucleus (Vme) neurons to oculomotor nuclei (III/IV) and their premotor neurons in interstitial nucleus of Cajal (INC)-a well-known pre-oculomotor center manipulating vertical-torsional eye movements. We hypothesized that these projections may interact with vestibulo-ocular signals during vertical-torsional VOR, because effects of gravity on jaw muscles and bones has been reported. Thus, we injected different anterograde tracers into the Vme and medial vestibular nucleus (MVN)-the subnuclear area particularly harboring excitatory vestibulo-ocular neurons, and immunostained III/IV motoneurons. Retrograde tracer was injected into the III in the same animals after dual anterograde tracers' injections. Under confocal microscope, we observed the Vme and MVN neuronal endings simultaneously terminated onto the same III/IV motoneurons and the same INC pre-oculomotor neurons. We consider that jaw muscle proprioceptive Vme neurons projecting to the III/IV and INC would sense spindle activity if the jaw muscle is stretched by gravity dragged mandible or connection between mandible and clavicle during head rolling. Therefore, the convergent innervation of the Vme and MVN neurons onto the oculomotor and pre-oculomotor nuclei would be a neuroanatomic substrate for interaction of masticatory proprioception with the vestibulo-ocular signals upon the oculomotor system during vertical-torsional VOR.

Numerous types of viruses have been found in human semen, which raises concerns about the sexual transmission of these viruses. The overall effect of semen on viral infection and transmission have yet to be fully investigated. In the present study, we aimed at the effect of seminal plasma (SP) on viral infection by focusing on the mumps viral (MuV) infection of HeLa cells. MuV efficiently infected HeLa cells in vitro. MuV infection was strongly inhibited by the pre-treatment of viruses with SP. SP inhibited MuV infection through the impairment of the virus’s attachment to cells. The antiviral activity of SP was resistant to the treatment of SP with boiling water, Proteinase K, RNase A, and DNase I, suggesting that the antiviral factor would not be proteins and nucleic acids. PNGase or PLA2 treatments did not abrogate the antiviral effect of SP against MuV. Further, we showed that the prostatic fluid (PF) showed similar inhibition as SP, whereas the epididymal fluid and seminal vesicle extract did not inhibit MuV infection. Both SP and PF also inhibited MuV infection of other cell types, including another human cervical carcinoma cell line C33a, mouse primary epididymal epithelial cells, and Sertoli cell line 15P1. Moreover, this inhibitory effect was not specific to MuV, as the herpes simplex virus 1, dengue virus 2, and adenovirus 5 infections were also inhibited by SP and PF. Our findings suggest that SP contains a prostate-derived pan-antiviral factor that may limit the sexual transmission of various viruses.

To improve the salt resistance of superabsorbent materials and the gel strength of superabsorbent materials after water absorption, a bagasse cellulose-based network structure composite superabsorbent (CAAMC) was prepared via graft copolymerization of acrylamide/acrylic acid (AM/AA) onto bagasse cellulose using silane coupling agent modified nano-CaCO3 (MNC) and N,N′-methylene bisacrylamide (MBA) as a double crosslinker. The acrylamide/acrylic acid was chemically crosslinked with modified nano-CaCO3 by C-N, and a stable double crosslinked (DC) network CAAMC was formed under the joint crosslinking of N,N′-methylene bisacrylamide and modified nano-CaCO3. Modified nano-CaCO3 plays a dual role of crosslinking agent and the filler, and the gel strength of composite superabsorbent is two times higher than that of N,N′-methylene bisacrylamide single crosslinking. The maximum absorbency of CAAMC reached 712 g/g for deionized water and 72 g/g for 0.9 wt% NaCl solution. The adsorption process of CAAMC was simulated by materials studio, and the maximum adsorption energy of amino and carboxyl groups for water molecules is −2.413 kJ/mol and −2.240 kJ/mol, respectively. According to the results of CAAMC soil water retention, a small amount of CAAMC can greatly improve the soil water retention effect.

The mumps virus (MuV) causes epidemic parotitis. MuV also frequently infects the testis and induces orchitis, an important etiological factor contributing to male infertility. However, mechanisms underlying MuV infection of the testis remain unknown. Here, we describe that sialic acid, AXL, and MER receptor tyrosine kinases regulate MuV entry and replication in mouse major testicular cells, including Sertoli and Leydig cells. Sialic acid, AXL, and MER were present in Sertoli and Leydig cells. Sialic acid specifically mediated MuV entry into Sertoli and Leydig cells, whereas both AXL and MER facilitated MuV replication within cells through the inhibition of cellular innate antiviral responses. Mechanistically, the inhibition of type 1 interferon signaling by AXL and MER is essential for MuV replication in Sertoli and Leydig cells. Our findings provide novel insights into the mechanisms behind MuV infection and replication in the testis.

Phagocytosis plays important roles both in homeostasis and under pathological conditions. Fcγ receptor-mediated phagocytosis has been exploited as an integral mechanism for antibody-based therapies. Unlike Fcγ receptor-mediated phagocytosis, MerTK-mediated phagocytic clearance is immunologically silent. Here, we describe a bispecific antibody approach to harness MerTK for targeted clearance without inducing proinflammatory cytokine release associated with Fcγ receptor engagement. We generated bispecific antibodies targeting live B cells or amyloid beta aggregates to demonstrate the feasibility and versatility of this new approach.

The proactive generation of anti-idiotypic antibodies (anti-IDs) against therapeutic antibodies with desirable properties is an important step in pre-clinical and clinical assay development supporting their bioanalytical programs. Here, we describe a robust platform to generate anti-IDs using rabbit single B cell sorting-culture and cloning technology by immunizing rabbits with therapeutic drug Fab fragment and sorting complementarity determining regions (CDRs) specific B cells using designed framework control as a negative gate to exclude non-CDRs-specific B cells. The supernatants of cultured B cells were subsequently screened for binding to drug-molecule by enzyme-linked immunosorbent assay and the positive hits of B cell lysates were selected for cloning of their immunoglobulin G (IgG) variable regions. The recombinant monoclonal anti-IDs generated with this method have high affinity and specificity with broad epitope coverage and different types. The recombinant anti-IDs were available for assay development to support pharmacokinetic (PK) and immunogenicity studies within 12 weeks from the start of rabbit immunization. Using this novel rapid and efficient in-house approach we have generated a large panel of anti-IDs against a series of 11 therapeutic antibody drugs and successfully applied them to the clinical assay development.

Abstract Background Infant nerve injury causes delayed adolescent neuropathic pain, but whether it also leads to psychiatric illness is unknown. Environmental enrichment (EE) increases social communication and activity. Thus, our goal was to test anxiety- and depression-like behaviors after infant peripheral nerve injury and evaluate the effect of environmental enrichment on these models of affective disorders. Methods Open field, elevated plus maze, sucrose preference, and pain behaviors (paw withdrawal threshold, spontaneous guarding score, and cold response to acetone) were measured in rats that received infant spared nerve injury (SNI). Enzyme-linked immune absorbent assay of cytokines was performed to evaluate the inflammatory response in the brain. Then, the ability of intracerebroventricular (ICV) injection of a microglia inhibitor, minocycline (MIN), and EE (a free-running wheel, a staircase, a plastic tunnel, a raised platform, and various colored balls) to reverse the infant SNI effects on behaviors and cytokines was examined. Results Infant nerve injury resulted in adolescent anxiety- and depression-like behaviors. The medial prefrontal cortex, basolateral amygdala, and ventral hippocampus were skewed to a pro-inflammatory profile. ICV injection of MIN reduced anxiety- and depression-like behaviors without affecting pain behaviors. In addition, ICV MIN skewed the brain towards an anti-inflammatory profile. Finally, environmental enrichment improved anxiety- and depression-like behaviors, as well as pain behaviors. EE increased brain IL-10 and decreased IL-1β and TNF-α. Conclusions Infant nerve injury induces adolescent anxiety- and depression-like behaviors and central nervous inflammation. Environmental enrichment reduces these behaviors by normalizing the inflammation balance in the brain.

The mangrove fern Acrostichum aureum is widely distributed in the Indo West-Pacific and Atlantic East-Pacific regions. Here we assembled and annotated its chloroplast genome based on the Illumina sequencing reads. The complete chloroplast genome of A. aureum was 154,805 bp in length with the GC content of 38.38%. It contains a large single copy (LSC) region of 82,826 bp and a small single copy (SSC) region of 21,617 bp, separated by a pair of inverted repeat region (IRs) of 25,181 bp each. It contains 84 protein coding genes, 27 tRNA genes, and four rRNA genes. Phylogenetic analysis shows that A. aureum is closest to Ceratopteris cornuta in the subfamily Parkerioideae. The chloroplast genome of A. aureum reported here offers a useful resource for its phylogeography and conservation genetics studies.

Heterotis and Heterocentron are two shrub genera in the tribe Melastomateae (Melastomataceae). Heterotis rotundifolia (Hr) and Heterocentron elegans (He) are both widely used as ornamental plants in the tropical regions. In this study, the complete chloroplast (cp) genomes of Hr and He were sequenced, assembled, and annotated. The cp genome sizes of Hr and He are 156,336 bp and 156,514 bp, respectively. The cp genome of Hr contains a total of 132 genes, including 87 protein-coding, 37 tRNA, and eight rRNA genes, while that of He has 131 genes, including 87 protein-coding, 36 tRNA, and eight rRNA genes. Phylogenetic analysis reveals that Hr is sister to Osbeckia stellata, while He is sister to Tibouchina longifolia.

Adiantum reniforme var. sinense, a rare and endangered fern endemic to Chongqing, China, has been listed as one of the National Key Protected Wild Plants (Class I) in China. Here we assembled its chloroplast genome (cp genome) using Illumina sequencing reads to offer a genetic resource for future conservation genetic studies. The complete cp genome of A. reniforme var. sinense was 150,109 bp in length with an overall GC content of 42.85%. It contains a large single copy (LSC) region of 83,274 bp and a small single copy (SSC) region of 21,459 bp, separated by a pair of inverted repeat regions (IRs) of 22,688 bp each. The cp genome contains 84 protein coding genes, 28 tRNA genes, four rRNA genes, and one pseudogene (ψrps16). Phylogenetic analysis showed that A. reniforme var. sinense clustered together with four other Adiantum species and was sister to A. capillus-veneris.

Colony-stimulating factor 1 (CSF1) and interleukin 34 (IL34) signal via the CSF1 receptor to regulate macrophage differentiation. Studies in IL34- or CSF1-deficient mice have revealed that IL34 function is limited to the central nervous system and skin during development. However, the roles of IL34 and CSF1 at homeostasis or in the context of inflammatory diseases or cancer in wild-type mice have not been clarified in vivo. By neutralizing CSF1 and/or IL34 in adult mice, we identified that they play important roles in macrophage differentiation, specifically in steady-state microglia, Langerhans cells, and kidney macrophages. In several inflammatory models, neutralization of both CSF1 and IL34 contributed to maximal disease protection. However, in a myeloid cell-rich tumor model, CSF1 but not IL34 was required for tumor-associated macrophage accumulation and immune homeostasis. Analysis of human inflammatory conditions reveals IL34 upregulation that may account for the protection requirement of IL34 blockade. Furthermore, evaluation of IL34 and CSF1 blockade treatment during Listeria infection reveals no substantial safety concerns. Thus, IL34 and CSF1 play non-redundant roles in macrophage differentiation, and therapeutic intervention targeting IL34 and/or CSF1 may provide an effective treatment in macrophage-driven immune-pathologies.

Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP) incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA) and Caucasian American (CA) CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients). Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somatic mutations in CaP across ancestral groups, which have implications for precision medicine strategies.

Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT) has been proposed as a potential treatment for obesity-linked disorders. Here, we describe the generation of a humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR) 1/βKlotho complex, a common receptor for FGF21 and FGF19. Using this molecule, we show that antibody-mediated activation of FGFR1/βKlotho complex in mice induces sustained energy expenditure in BAT, browning of white adipose tissue, weight loss, and improvements in obesity-associated metabolic derangements including insulin resistance, hyperglycemia, dyslipidemia and hepatosteatosis. In mice and cynomolgus monkeys, FGFR1/βKlotho activation increased serum high-molecular-weight adiponectin, which appears to contribute over time by enhancing the amplitude of the metabolic benefits. At the same time, insulin sensitization by FGFR1/βKlotho activation occurs even before the onset of weight loss in a manner that is independent of adiponectin. Together, selective activation of FGFR1/βKlotho complex with a long acting therapeutic antibody represents an attractive approach for the treatment of type 2 diabetes and other obesity-linked disorders through enhanced energy expenditure, insulin sensitization and induction of high-molecular-weight adiponectin.

The genus Rhizophora is one of the most important components of mangrove forests. It is an ideal system for studying biogeography, molecular evolution, population genetics, hybridization and conservation genetics of mangroves. However, there are no sufficient molecular markers to address these topics. Here, we developed 77 pairs of nuclear gene primers, which showed successful PCR amplifications across all five Rhizophora species and sequencing in R. apiculata. Here, we present three tentative applications using a subset of the developed nuclear genes to (I) reconstruct the phylogeny, (II) examine the genetic structure and (III) identify natural hybridization in Rhizophora. Phylogenetic analyses support the hypothesis that Rhizophora had disappeared in the Atlantic-East Pacific (AEP) region and was re-colonized from the IWP region approximately 12.7 Mya. Population genetics analyses in four natural populations of R. apiculata in Hainan, China, revealed extremely low genetic diversity, strong population differentiation and extensive admixture, suggesting that the Pleistocene glaciations, particularly the last glacial maximum, greatly influenced the population dynamics of R. apiculata in Hainan. We also verified the hybrid status of a morphologically intermediate individual between R. apiculata and R. stylosa in Hainan. Based on the sequences of five nuclear genes and one chloroplast intergenic spacer, this individual is likely to be an F1 hybrid, with R. stylosa as its maternal parent. The nuclear gene markers developed in this study should be of great value for characterizing the hybridization and introgression patterns in other cases of this genus and testing the role of natural selection using population genomics approaches.

Neurons exposed to zinc exhibit activation of poly(ADP-ribose) polymerase-1 (PARP-1), an enzyme that normally participates in DNA repair but promotes cell death when extensively activated. Endogenous, vesicular zinc in brain is released to the extracellular space under conditions causing neuronal depolarization. Here, we used a rat model of insulin-induced hypoglycemia to assess the role of zinc release in PARP-1 activation and neuronal death after severe hypoglycemia. Zinc staining with N-(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) showed depletion of presynaptic vesicular zinc from hippocampal mossy fiber terminals and accumulation of weakly bound zinc in hippocampal CA1 cell bodies after severe hypoglycemia. Intracerebroventricular injection of the zinc chelator calcium ethylene-diamine tetraacetic acid (CaEDTA) blocked the zinc accumulation and significantly reduced hypoglycemia-induced neuronal death. CaEDTA also attenuated the accumulation of poly(ADP-ribose), the enzymatic product of PARP-1, in hippocampal neurons. These results suggest that zinc translocation is an intermediary step linking hypoglycemia to PARP-1 activation and neuronal death.

Autoimmune hepatitis (AIH) is a severe type of chronic liver disease. The lack of appropriate animal models has resulted in a limited understanding regarding the etiology of AIH. Here, we demonstrated that mice deficient in Tyro3, Axl and Mer (TAM) receptor tyrosine kinases (RTKs) developed persistent inflammatory liver damage resembling AIH. Tyro3(-/-)Axl(-/-)Mer(-/-) triple mutant (TAM(-/-)) mice exhibited chronic hepatitis, manifested by progressive appearance of interface hepatitis, immune cell infiltrations and elevated inflammatory cytokine levels in the liver. Accordingly, increased levels of transaminases were observed. Moreover, characteristic autoantibodies and high levels of plasma immunoglobulin G for AIH were detected as TAM(-/-) mice aged. Finally, we provided evidence that the liver damage in TAM(-/-) mice mainly result from bone marrow-derived cells and could be rescued by transplantation of WT bone marrow cells. Results suggest that TAM RTKs play an important role in maintaining immune tolerance of the liver.

Introduction. Concern regarding overtreatment of prostate cancer (CaP) is leading to increased attention on active surveillance (AS). This study examined CaP survivors on AS and compared secondary treatment patterns and overall survival by race/ethnicity. Methods. The study population consisted of CaP patients self-classified as black or white followed on AS in the Center for Prostate Disease Research (CPDR) multicenter national database between 1989 and 2008. Secondary treatment included radical prostatectomy (RP), external beam radiation therapy or brachytherapy (EBRT-Br), and hormone therapy (HT). Secondary treatment patterns and overall survival were compared by race/ethnicity. Results. Among 886 eligible patients, 21% were black. Despite racial differences in risk characteristics and secondary treatment patterns, overall survival was comparable across race. RP following AS was associated with the longest overall survival. Conclusion. Racial disparity in overall survival was not observed in this military health care beneficiary cohort with an equal access to health care.

Background and Objectives The molecular mechanisms regulating megakaryocytopoiesis and hemostasis remain largely unknown. The Tyro 3 subfamily of receptor tyrosine kinases (RTK), which is composed of three members (Tyro 3, Axl and Mer), plays important roles in various tissues, such as those in the nervous, immune and reproductive systems. Here, we investigate the roles of the Tyro 3 RTK subfamily in regulating megakaryocytopoiesis and hemostasis.Design and Methods Single, double, and triple knock-out mice for the three Tyro 3 RTK were used in the study. Bleeding time, platelet count, megakaryocyte count, megakaryocyte ploidy, rate of proplatelet formation, platelet aggregation and ATP release were used as criteria to evaluate hemostasis, megakaryocytopoiesis and platelet function.Results Mice lacking all three receptors had impaired hemostasis and mild thrombocytopenia, which may be due to platelet dysfunction and defective megakaryocytopoiesis. Mice lacking different combinations of two receptors of the Tyro 3 RTK subfamily had normal platelet counts in peripheral blood, but exhibited impaired hemostasis and platelet function. Although knock-out mice for any single receptor had normal hemostasis and megakaryocytopoiesis, they exhibited a mild platelet dysfunction.Interpretation and Conclusions The Tyro 3 RTK subfamily plays important roles in regulating hemostasis, megakaryocytopoiesis and platelet function.

Purification treatment is needed to control the concentration of SO42+ and Ca2+ in brine to solve the problem of low electrolysis efficiency for the electrolysis of KCl solution in the chlor-alkali industry. However, the traditional barium method to remove SO42+ faces the problem of high cost and environmental pollution. Herein, inexpensive and environmentally friendly anhydrous calcium chloride was used as the precipitant to replace barium chloride. The conditions for SO42+ removal at room temperature were optimized by studying the precipitant doping ratio, reaction time, and stirring speed. The results indicated that the concentration of SO42+ in brine could be reduced to less than 5 g L-1 at a raw material ratio of nCa2+ to nSO42+ of 1.1: 1, a stirring speed of 300 rpm, and a reaction time of 120 min. Ca2+ in the solution could be removed by introducing carbon dioxide, and the removal rate of Ca2+could reach 99.89% by adjusting the pH of the solution to an appropriate value. This work paves a new way for efficient brine refining to boost sustainable development in the chloralkali industry. [ABSTRACT FROM AUTHOR]