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This research presents a method based on deep learning for the reverse design of sound-absorbing structures. Traditional methods require time-consuming individual numerical simulations followed by cumbersome calculations, whereas the deep learning design method significantly simplifies the design process, achieving efficient and rapid design objectives. By utilizing deep neural networks, a mapping relationship between structural parameters and the sound absorption coefficient curve is established. The forward network predicts the sound absorption coefficient curve, while the reverse network enables the on-demand design of structural parameters for broadband high sound absorption. During the design process, a mean squared error (MSE) below 0.0001 is achieved. The accuracy of the proposed design method is validated through examples. The results demonstrate that the trained deep learning neural network could effectively replace the complex physical mechanisms between structural parameters and sound absorption coefficient curves. This deep learning design method could also be extended to other types of metamaterial reverse designs, significantly enhancing the efficiency of complex metamaterial designs. Lightweight design is crucial for energy saving and emission reduction. With the total mass and average sound absorption coefficient of sound-absorbing materials as targets, the NSGA-II algorithm has been used for multi-objective optimization design. The optimized average sound absorption coefficient increased by 4.84%, and the total material mass was reduced by 18.98%., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Vasoepididymostomy (VE) is an important surgical treatment to achieve natural conception for patients with obstructive azoospermia (OA), and only unilateral VE can be performed under certain conditions, such as OA patients with congenital unilateral absence of the vas deferens (CUAVD) and some acquired OA. There is a lack of relevant reports assessing the clinical outcomes of unilateral VE in OA patients with different causes. This study is aimed to describe the clinical features and evaluate treatments and outcomes of unilateral single-armed VE in OA patients., Methods: From December 2015 to June 2021, 46 OA patients (including 13 CUAVD-associated OA and 33 acquired OA) underwent unilateral single-armed VE in Shanghai General Hospital (Shanghai, China). Patient information, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated., Results: Obstruction in distal of unilateral vas deferens (16/46) was the most common cause for OA patients underwent unilateral VE, and CUAVD accounts for 28.4% (13/46). The overall patency rate was 50.0% (23/46), with 38.5% (5/13) for the CUAVD group and 54.5% (18/33) for the acquired group (p > 0.05). The natural pregnancy rates in CUAVD group and acquired group were 20.0% and 33.3%, respectively (p > 0.05)., Conclusions: These findings suggest unilateral single-armed VE can achieve high patency and pregnancy rates in OA patients, whether for CUAVD or acquired OA patients., Competing Interests: Declarations. Ethics approval and consent to participate: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This study obtained approval from the Ethics Committee of Shanghai General Hospital (No.: 2017KY020-2) and informed consent was obtained from all individual participants. Consent for publication: All authors have completed the ICMJE uniform disclosure form. The authors have no conflicts of interest to declare. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

The composition and cellular heterogeneity of the corpus cavernosum (CC) microenvironment have been characterized, but the spatial heterogeneity at the molecular level remains unexplored. In this study, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing to comprehensively chart the spatial cellular landscape of the human and rat CC under normal and disease conditions. We observe differences in the proportions of cell subtypes and marker genes between humans and rats. Based on the analysis of the fibroblast (FB) niche, we also find that the enrichment scores of mechanical force signaling vary across different regions and correlate with the spatial distribution of FB subtypes. In vitro, the soft and hard extracellular matrix (ECM) induces the differentiation of FBs into apolipoprotein (APO)+ FBs and cartilage oligomeric matrix protein (COMP)+ FBs, respectively. In summary, our study provides a cross-species and physiopathological transcriptomic atlas of the CC, contributing to a further understanding of the molecular anatomy and regulation of penile erection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Due to rapid urbanization and climate change, cities face hidden drought risks. A single drought index may inadequately reflect urban meteorological drought. The indicator weight combination method does not fully consider index correlation and weight. This study constructed an urban meteorological drought evaluation index system and developed the Composite Fuzzy Matter Element Meteorological drought Comprehensive Index (CFEMCI) by combining the moment estimation weighting model. Analyzing Zhengzhou City from 2000 to 2019, CFEMCI effectively captured meteorological drought events, with a probability of detection (POD) > 0.78, critical success index (CSI) > 0.70, false alarm rate (FAR) < 0.13 and failure ratio (FR) < 0.22. Most meteorological droughts were classified as Grade I (no drought), with 26% being light and moderate (Grades II-III). Droughts mainly occurred in spring, and the summer drought showed a more significantly aggravating trend. This index provides reliable urban drought monitoring and supports disaster prevention and mitigation efforts., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

The growing demand for electrified heating, electrified transportation, and power-intensive data centres challenge distribution networks. If electrification projects are carried out without considering electrical distribution infrastructure, there could be unexpected blackouts and financial losses. Datasets containing real-world distribution network information are required to address this. However, the existing dataset at NERC that covers the whole of Great Britain (GB) does not provide information about demand and capacity, which is insufficient for evaluating the connection feasibility. Although each distribution network operator (DNO) has detailed network information for their supply area, the information is scattered in separate files and different formats even within the same DNO, which limits usability. On the other hand, studying the coupling between energy systems and societal attributes such as household heating is important in promoting social welfare, which calls for more comprehensive datasets that integrate the social data and the energy network data. However, social datasets are usually provided on a regional basis, and the link to energy networks is not straightforward, which explains the lack of the comprehensive datasets. To fill these gaps, this paper introduces two datasets. The first is the main dataset for the GB distribution networks, collecting information on firm capacity, peak demands, locations, and parent transmission nodes (grid supply points, namely GSPs) for all primary substations (PSs). PSs are a crucial part of UK distribution networks and are at the lowest voltage level (11 kV) with publicly available data. Substation firm capacity and peak demand facilitate an understanding of the remaining room in the existing network. The parent GSP information helps link the released datasets to transmission networks. These datasets are collected, standardised, and merged from various files with different formats published by the six DNOs in GB, using a Python script and manual validation. The second dataset extends the main network dataset, linking each PS to the number of households that use different types of central heating recorded in census data (Census in year 2021 for England and Wales, and Census 2011 for Scotland as the up-to-date Census 2022 data is not fully released). The derivation of the second dataset is based on the locations of PSs collected in the main dataset with appropriate assumptions. The derivation process may be replicated to integrate other social datasets. The datasets have the following reuse potentials: 1) Given the PS demand, capacity, and locations in our datasets, users can estimate the connection feasibility and evaluate the optimal deployment locations for different energy technologies, including electric vehicles, heat pumps, and the growing data centres, under different scenarios and at a national scale. These evaluations are beneficial not only for academic research, but also for industrial planning and policy making. 2) Our extended dataset links household information to distribution networks. The integrated information facilitates cross-disciplinary research and analysis across social science, energy policy, and power systems. 3) The network demand and capacity information provided by the datasets can also help with realistic parameter settings to improve the accuracy of case studies in broader power system research., (© 2024 The Author(s).)

The power capacity of reflectarray antennas (RAs) is investigated through full-wave simulations and high-power microwave (HPM) experiments in this paper. In order to illustrate the results in detail, two RA elements are designed. The simulated power handling capacity of two RA elements are 7.17 MW/m 2 and 2.3 GW/m 2 , respectively. To further study the HPM RA, two RA prototypes operating at 2.8 GHz are constructed with the aperture size of 1 m × 1 m. Simulations and experimental measurements are conducted for the two prototypes. The experimental results demonstrate that, even when subjected to 1 GW of power, the radiation beam of the RA with the second elements can still propagate in the intended direction. This research will establish a basis for advancing the practicality of RAs in HPM applications.

Fuel poverty, a pressing issue affecting social prosperity, has been exacerbated during the energy crisis triggered by the Russia-Ukraine conflict. This problem can be more severe for off-gas regions. Our study investigates heat pumps (HPs) as a cost-effective alternative to off-gas heating to alleviate fuel poverty in England and Scotland. We analyze regional fuel poverty rates and the associated greenhouse gas emission reduction by replacing all off-gas heating with HPs, observing positive effects under pre-crisis and crisis conditions, with existing government support for HP upfront costs. HP rollout can burden distribution networks especially for certain regions, but our correlation analysis shows that high benefits do not always come with network costs at the regional level, and we identify "priority" regions with low costs and high benefits. These findings provide valuable insights for policymakers to address fuel poverty and reach decarbonization. The methodology is adaptable to other countries with appropriate datasets., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Aortic aneurysm and dissection are complicated diseases having both high prevalence and mortality. It is usually diagnosed at advanced stages and posing diagnostic and therapeutic challenges due to the limitations of current detecting methods for aortic dissection used in clinics. Metabonomics demonstrated its great potential capability in the early diagnosis and personalized treatment of several diseases. Emerging evidence suggests that metabolic disorders including amino acid metabolism, glycometabolism, and lipid metabolism disturbance are involved in the pathogenesis of aortic aneurysm and dissection by affecting multiple functional aortic cells. The purpose of this review is to provide new insights into the metabolism alterations and their related regulatory mechanisms with a focus on recent advances and findings and provide a theoretical basis for the diagnosis, prevention, and drug development for aortic aneurysm and dissection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

This paper introduces a novel single-layer microstrip patch element designed to achieve a wide beamwidth, in order to address the growing demand for wide-angle scanning capabilities in modern phased array systems. The proposed element, comprising a slot-etched circular patch and an array of metallized holes arranged in square rings, offers a unique approach to beam shaping. By carefully adjusting parameters such as the slot structure and feeding position, our element is engineered to simultaneously excite both the TM 01 and TM 21 modes, a key feature that contributes to its wide beamwidth characteristics. Through the constructive interference of these modes, our element demonstrates a remarkable 3 dB beamwidth of approximately 150° in both principal planes, showcasing its potential for wide-angle scanning applications. To validate the practical performance of this proposed element, two linear phased arrays are manufactured and experimentally evaluated. The simulation results confirm the wide-angle scanning capability of the antennas in both the E-plane and H-plane. Furthermore, the experimental assessment demonstrates that these linear phased arrays can effectively generate scanning beams within a frequency range of 25 GHz to 28 GHz, covering a wide angular range from -60° to 60°, while maintaining a gain loss within 3 dB. This innovative design approach not only offers a promising solution for achieving a wide beamwidth in microstrip patch elements, but also holds significant potential for the development of cost-effective phased arrays with wide-angle scanning capabilities, making it a valuable contribution to the advancement of phased array technology.

Nanocapsule preparation technology, as an emerging technology with great development prospects, has uniqueness and superiority in various industries. In this paper, the preparation technology of nanocapsules was systematically divided into three categories: physical methods, chemical methods, and physicochemical methods. The technological innovation of different methods in recent years was reviewed, and the mechanisms of nanocapsules prepared via emulsion polymerization, interface polymerization, layer-by-layer self-assembly technology, nanoprecipitation, supercritical fluid, and nano spray drying was summarized in detail. Different from previous reviews, the renewal iteration of core-shell structural materials was highlighted, and relevant illustrations of their representative and latest research results were reviewed. With the continuous progress of nanocapsule technology, especially the continuous development of new wall materials and catalysts, new preparation technology, and new production equipment, nanocapsule technology will be used more widely in medicine, food, cosmetics, pesticides, petroleum products, and many other fields.

Background: This study's objective was to investigate the predictors for severe anemia, severe leukopenia, and severe thrombocytopenia when amphotericin B deoxycholate-based induction therapy is used in HIV-infected patients with talaromycosis., Methods: A total of 170 HIV-infected patients with talaromycosis were enrolled from January 1st, 2019, to September 30th, 2020., Results: Approximately 42.9%, 20.6%, and 10.6% of the enrolled patients developed severe anemia, severe leukopenia, and severe thrombocytopenia, respectively. Baseline hemoglobin level < 100 g/L (OR = 5.846, 95% CI: 2.765 ~ 12.363), serum creatinine level > 73.4 µmol/L (OR = 2.573, 95% CI: 1.157 ~ 5.723), AST/ALT ratio > 1.6 (OR = 2.479, 95% CI: 1.167 ~ 5.266), sodium level ≤ 136 mmol/liter (OR = 4.342, 95% CI: 1.747 ~ 10.789), and a dose of amphotericin B deoxycholate > 0.58 mg/kg/d (OR = 2.504, 95% CI:1.066 ~ 5.882) were observed to be independent risk factors associated with the development of severe anemia. Co-infection with tuberculosis (OR = 3.307, 95% CI: 1.050 ~ 10.420), and platelet level (per 10 × 109 /L) (OR = 0.952, 95% CI: 0.911 ~ 0.996) were shown to be independent risk factors associated with the development of severe leukopenia. Platelet level < 100 × 10 9 /L (OR = 2.935, 95% CI: 1.075 ~ 8.016) was identified as the independent risk factor associated with the development of severe thrombocytopenia. There was no difference in progression to severe anemia, severe leukopenia, and severe thrombocytopenia between the patients with or without fungal clearance at 2 weeks. 10 mg on the first day of amphotericin B deoxycholate was calculated to be independent risk factors associated with the development of severe anemia (OR = 2.621, 95% CI: 1.107 ~ 6.206). The group receiving a starting amphotericin B dose (10 mg, 20 mg, daily) exhibited the highest fungal clearance rate at 96.3%, which was significantly better than the group receiving a starting amphotericin B dose (5 mg, 10 mg, 20 mg, daily) (60.9%) and the group receiving a starting amphotericin B dose (5 mg, 15 mg, and 25 mg, daily) (62.9%)., Conclusion: The preceding findings reveal risk factors for severe anemia, severe leukopenia, and severe thrombocytopenia. After treatment with Amphotericin B, these severe adverse events are likely unrelated to fungal clearance at 2 weeks. Starting amphotericin B deoxycholate at a dose of 10 mg on the first day may increase the risk of severe anemia but can lead to earlier fungal clearance., Trial Registration: ChiCTR1900021195. Registered 1 February 2019., (© 2023. BioMed Central Ltd., part of Springer Nature.)

As a global health threat, bladder cancer (BC) is a common urological disease characterized by a high risk of progression and recurrence. Icariside II (ICA-II), a flavonol glycoside, exhibits antitumor ability in various tumors. However, there is no systematic study exploring the pharmacological mechanism of ICA-II in BC. We used public databases to obtain potential targets of ICA-II and related genes in BC. Bioinformatics analysis and molecular docking were used to identify potential targets and signaling pathways. Then, MTT, cell cycle assays and western blot (WB) were used to validate the predicted pathways in bladder cell lines, and in situ bladder cancer models were also established to verify the effect of ICA-II. Our research demonstrated that these ICA-II hub genes were related to the cell cycle. Then, our molecular docking analysis confirmed the interaction between ICA-II and CCNB1. In addition, our in vitro experiment demonstrated that ICA-II restrained the proliferation of BC cells mainly by blocking the cell cycle. WB also verified that ICA-II decreased the expression levels of CCNB1. In situ BC models showed that ICA-II had no hepatotoxicity or nephrotoxicity and could suppress the growth of in situ BC. In summary, during this study, we found that ICA-II had low toxicity in the kidney and liver. Network pharmacology was used, and both cell and animal experiments verified that ICA-II has a good therapeutic effect on bladder cancer, which may inhibit the proliferation and progression of bladder cancer by blocking the cell cycle of BC cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Cavernous nerve injury-induced erectile dysfunction caused by pelvic surgery or trauma is refractory to conventional medications and required an alternative treatment. Low-intensity pulsed ultrasound is a noninvasive mechanical therapy that promotes nerve regeneration., Objectives: To investigate the therapeutic effect and potential mechanism of low-intensity pulsed ultrasound in the treatment of neurogenic erectile dysfunction., Materials and Methods: Thirty rats were randomly divided into the sham-operated group, bilateral cavernous nerve injury group, and bilateral cavernous nerve injury + low-intensity pulsed ultrasound group. The erectile function was assessed 3 weeks after daily low-intensity pulsed ultrasound treatment. The penile tissues and cavernous nerve tissues were harvested and subjected to histologic analysis. Primary Schwann cells and explants were extracted from adult rats. The effects of low-intensity pulsed ultrasound on proliferation, migration, and nerve growth factor expression of Schwann cells and axonal elongation were examined in vitro. RNA sequencing and western blot assay were applied to predict and verify the molecular mechanism of low-intensity pulsed ultrasound-induced Schwann cell activation., Results: Our study showed that low-intensity pulsed ultrasound promoted Schwann cells proliferation, migration, and neurotrophic factor nerve growth factor expression. Meanwhile, low-intensity pulsed ultrasound exhibits a stronger ability to enhance Schwann cells-mediated neurite outgrowth of major pelvic ganglion neurons and major pelvic ganglion/cavernous nerve explants in vitro. In vivo experiments demonstrated that the erectile function of the rats in the bilateral cavernous nerve injury + low-intensity pulsed ultrasound group was significantly higher than those in the bilateral cavernous nerve injury groups. Moreover, the expression levels of smooth muscle and cavernous endothelium also increased significantly in the bilateral cavernous nerve injury + low-intensity pulsed ultrasound group. In addition, we observed the higher density and number of cavernous nerve regenerating axons in the bilateral cavernous nerve injury + low-intensity pulsed ultrasound group, indicating that low-intensity pulsed ultrasound promotes axonal regeneration following cavernous nerve injury in vivo. RNA sequencing analysis and bioinformatic analysis suggested that low-intensity pulsed ultrasound might trigger the activation of the PI3K/Akt pathway. Western blot assay confirmed that low-intensity pulsed ultrasound activated Schwann cells through TrkB/Akt/CREB signaling., Conclusions: Low-intensity pulsed ultrasound promoted nerve regeneration and ameliorated erectile function by enhancing Schwann cells proliferation, migration, and neurotrophic factor nerve growth factor expression. The TrkB/Akt/CREB axis is the possible mechanism of low-intensity pulsed ultrasound-mediated Schwann cell activation. Low-intensity pulsed ultrasound-based therapy could be a novel potential treatment strategy for cavernous nerve injury-induced neurogenic erectile dysfunction., (© 2023 American Society of Andrology and European Academy of Andrology.)

Head and neck cancer (HNC) is one of the most common cancers on the planet, with approximately 600,000 new cases diagnosed and 300,000 deaths every year. Research into the biological basis of HNC has advanced slowly over the past decades, which has made it difficult to develop new, more effective treatments. The patient-derived organoids (PDOs) are made from patient tumor cells, resembling the features of their tumors, which are high-fidelity models for studying cancer biology and designing new precision medicine therapies. In recent years, considerable effort has been focused on improving "organoids" technologies and identifying tumor-specific medicine using head and neck samples and a variety of organoids. A review of improved techniques and conclusions reported in publications describing the application of these techniques to HNC organoids is presented here. Additionally, we discuss the potential application of organoids in head and neck cancer research as well as the limitations associated with these models. As a result of the integration of organoid models into future precision medicine research and therapeutic profiling programs, the use of organoids will be extremely significant in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qi, Tan, Zhang, Zhou, Chen, Zha, Wang and Wen.)

At present, the technology used for the extraction and purification of Camellia oleifera saponins generally has the problems of high cost and low purity, and the quantitative detection of Camellia oleifera saponins also has the problems of low sensitivity and easy interference from impurities. To solve these problems, this paper aimed to use liquid chromatography for the quantitative detection of Camellia oleifera saponins, and to adjust and optimize the related conditions. In our study, the average recovery of Camellia oleifera saponins obtained was 100.42%. The RSD of precision test was 0.41%. The RSD of the repeatability test was 0.22%. The detection limit of the liquid chromatography was 0.06 mg/L, and the quantification limit was 0.2 mg/L. In order to improve the yield and purity, the Camellia oleifera saponins were extracted from Camellia oleifera Abel. seed meal by methanol extraction. Then, the extracted Camellia oleifera saponins were extracted with an ammonium sulfate/propanol aqueous two-phase system. We optimized the purification process of formaldehyde extraction and aqueous two-phase extraction. Under the optimal purification process, the purity of Camellia oleifera saponins extracted by methanol was 36.15%, and the yield was 25.24%. The purity of Camellia oleifera saponins obtained by aqueous two-phase extraction was 83.72%. Thus, this study can provide a reference standard for rapid and efficient detection and analysis of Camellia oleifera saponins for industrial extraction and purification.

Ni-20Cr-Eu 2 O 3 composites were designed as new control rod materials and were synthesized from Ni, Cr, and Eu 2 O 3 mixture powders via ball milling and vacuum hot pressing. During ball milling, Eu 2 O 3 was fined, nano-crystallized, amorphized, and then dissolved into matrix. The effect of Eu 2 O 3 content on the microstructure and mechanics was researched, and the corresponding mechanism was discussed. The relative densities, grain sizes, and microhardness increased when Eu 2 O 3 content increased. According to the TEM observations, Eu 2 O 3 particles showed a semi-coherent relationship with the matrix. The results of mechanical property testing showed that the ultimate tensile strength, yield strength, and elongation decreased with the Eu 2 O 3 content increased. The maximum ultimate tensile strength, yield strength, and elongation were 741 MPa, 662 MPa, and 4%, respectively, with a 5 wt.% Eu 2 O 3 addition. The experimental strengths were well matched with the theoretical values calculated by the strengthening mechanisms indicating that this method was highly effective for predicting the mechanical properties of Ni-20Cr-Eu 2 O 3 composites.

Introduction: Cisplatin (cis-diamminedichloroplatinum II, CDDP), a drug widely used for cancer worldwide, may affect erectile function, but its side effects have not received enough attention. To investigate the effect of CDDP on erectile function and its possible mechanism., Methods: Sprague-Dawley rats were intraperitoneally administered CDDP (CDDP group) or the same volume of normal saline (control group). Erectile function was evaluated after a one-week washout. Then, histologic changes in the corpus cavernosum and cavernous nerve (CN) were measured. Other Sprague-Dawley rats were used to isolate the major pelvic ganglion and cavernous nerve (MPG/CN). RSC96 cells were then treated with CDDP. SA-β-gal staining was used to identify senescent cells, and qPCR was used to detect the senescence-associated secretory phenotype (SASP). Finally, the supernatant of RSC96 cells was used to culture MPG/CN. Erectile function was measured after administration of CDDP. The cavernosum levels of α-SMA, CD31, eNOS, and γ-H2AX, the apoptosis rate and the expression of p16, p21 and p53 in CN were also assayed. The senescent phenotype of RSC96 cells treated with CDDP was identified, and neurite growth from the MPG/CN was photographed and measured., Results: The CDDP group had a significantly lower ICP/MAP ratio than the control group. Compared to the control group, the CDDP group exhibited significantly lower α-SMA, CD31 and eNOS levels and significantly higher γ-H2AX and apoptosis rates in corpus cavernosum. In addition, CDDP increased some senescence markers p16, p21 and p53 in CN. In vitro , CDDP induced RSC96 senescence and SASP, and the supernatant of senescent cells slowed neurite outgrowth of MPG/CN., Discussions: CDDP treatment could induce erectile dysfunction, by affecting the content of endothelial and smooth muscle and causing SASP in CN. The results indicate that CDDP treatment should be considered as a risk factor for ED. Clinicians should pay more attention to the erectile function of cancer patients who receive CDDP treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yin, Zhou, Zhou, Zhao, Hu, Xiao, Niu, Peng, Dai and Tang.)

This paper proposes a novel metasurface-based monopulse antenna. A multimode pyramidal horn with four ports is selected as the feed of the proposed monopulse antenna. The 3-dB couplers and the optimized waveguide phase shifters are employed to design the monopulse comparator. In order to obtain good sum and difference beams performance, metasurfaces are mounted on a bowl structure to radiate the electromagnetic wave from the sub-reflector. An experimental prototype of the proposed design has been fabricated and measured at Ku-band. The measured results show that the gain ratio between the sum and difference beams is 2.8 dB and 3.7 dB, respectively. More importantly, the peak gain of the sum beam at 16 GHz is 27.1 dB, without considering the loss of the comparator, with a corresponding aperture efficiency of about 41.4%. This indicates that the proposed structure is beneficial for improving the sum and difference beams performance of the monopulse antenna, which is suitable for tracking platforms.

Background: Accumulating data have shown that high expression of CD73 is associated with poor prognosis in various cancers, however the role and significance of CD73 in clear-cell renal cell carcinoma (ccRCC) still remain unclear. The present study aims to evaluate the prognostic significance of CD73 in ccRCC and explore the potential function in vitro and in vivo ., Methods: Firstly, the expression of CD73 in ccRCC was detected using clinical tissues and verified using TCGA and GEO data. Immunohistochemistry and Kaplan-Meier test were performed for survival analysis. Furthermore, knockdown or overexpression of CD73 was conducted by lentivirus transfection in ccRCC cells. MTT assay, colony formation assay, wound healing assay, transwell assay and xenograft assay were performed in vitro or in vivo ., Results: Our results showed that CD73 was highly expressed in ccRCC, and high expression of CD73 was negatively correlated with prognosis. In addition, CD73 promoted cell proliferation and migration in vitro and in vivo . Our data also showed that CD73 played both enzymatic and non-enzymatic functions in the regulation of cell proliferation and migration in ccRCC., Conclusions: These findings suggested that CD73 might promote the growth of ccRCC and contribute to poor prognosis. Taken together, CD73 may be a potential therapeutic target in ccRCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-544/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

A novel parameter identification method for locally linear radial basis function-based autoregressive models in presence of colored noises is proposed in this paper. Taking advantage of the global nonlinear and local linear structural characteristics of the models, two dynamical criterion functions are constructed based on the separated parameters to realize the dynamical acquisition and utilization of the entire process data. Two recursive gradient sub-algorithms are derived for estimating the separated parameters by using the nonlinear gradient optimization. To coordinate the associated variables existing in the sub-algorithms and to estimate the unmeasurable noise terms, we combine the sub-algorithms and propose a two-stage extended recursive gradient (2S-ERG) algorithm. In addition, an extended recursive gradient algorithm is given as a comparison. The feasibility of the 2S-ERG algorithm is validated by numerical simulations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 ISA. Published by Elsevier Ltd. All rights reserved.)

Introduction: The aims of this study were to investigate the risk factors for bacterial infections (BIs) and the association of BIs with the progression to acute-on-chronic liver failure (ACLF) in patients with hepatitis B virus (HBV)-related compensated liver cirrhosis and severe hepatitis flares., Methods: A total of 237 patients were retrospectively reviewed. Baseline biochemical characteristics were compared between patients with and without the occurrence of BIs and progression to ACLF. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for ACLF before and after 1:1 propensity score matching., Results: Forty-eight (20.3%) patients progressed to ACLF after admission. Additionally, 136 (57.4%) patients progressed to hepatic decompensation (HD) and 52 (21.9%) patients had BIs before the development of ACLF. Patients with BIs had significantly higher incidences of HD (84.6%) and ACLF (46.2%) than those without BIs (49.7% and 13.0%, respectively; P < 0.01). CTP score (OR 1.660, 95% CI 1.267-2.175) and MELD-Na score (OR 1.082, 95% CI 1.010-1.160) were independent risk factors for BIs. BIs (OR 4.037, 95% CI 1.808-9.061), CLIF-SOFA score (OR 2.007, 95% CI 1.497-2.691), and the MELD-Na score (OR 1.167, 95% CI 1.073-1.260) were independent risk factors for the progression to ACLF. BIs (OR 4.730, 95% CI 1.520-14.718) were also an independent risk factor for the progression to ACLF after propensity score matching., Conclusion: High CTP and MELD-Na scores are risk factors for BIs, and BIs are risk factors for the progression to ACLF in patients with HBV-related compensated liver cirrhosis and severe hepatitis flares., (© 2022. The Author(s).)

Selective serotonin reuptake inhibitors (SSRIs) are widely used for a variety of diseases, and their impact on semen quality is unclear. We performed a systematic search in PubMed and Embase, and after a strict screening, we included 4 studies with a total of 222 male participants. In result, SSRIs reduced normal sperm morphology (95% CI [-16.29, -3.77], p = 0.002), sperm concentration (95%CI [-43.88, -4.18], p = 0.02), sperm motility (95%CI [-23.46, -0.47], p = 0.04) and sperm DNA fragmentation index (DFI) (95% CI [6.66,21.93], p = 0.0002), without a statistically significant effect on semen volume (95%CI [-0.75,0.65], p = 0.89). Moreover, the impact on both sperm morphology and sperm concentration were observed within the 3-month period of SSRIs use. In general, our meta-analysis showed that SSRIs have a negative effect on semen quality. More larger, randomized, well-controlled clinical studies should be conducted to support our conclusion., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, He, Zhou, Zhao, Lin, Huang, Xie, Yue and Tang.)

Background: Nephrolithiasis is a common complication of primary hyperparathyroidism (PHPT), and the recurrence of nephrolithiasis in patients with PHPT is also an urgent concern. What is worse, there is a scarcity of recommended evaluation to predict the risk of nephrolithiasis recurrence in patients with PHPT. This study was aimed to develop and validate a nomogram to facilitate risk assessment in patients with PHPT., Methods: A total of 197 patients with PHPT were retrospectively included in this study from September 2016 to August 2021. Patients' demographic data, blood test parameters, urinalysis, stone parameters, and surgical intervention were collected. Extracted variables were submitted to a least absolute shrinkage and selection operator (LASSO) regression model. A nomogram was built and validated according to the area under the curve (AUC) value, calibration curve, and decision curve analysis., Results: According to the LASSO regression and logistic regression analyses, five predictors were derived from 22 variables: creatinine, uric acid, bilateral stone, multiplicity, and surgery. The AUC and concordance index of the training cohort and validation cohort were 0.829 and 0.856, and 0.827 and 0.877, respectively. The calibration curve analysis and the decision curve analysis showed that the nomogram had an adequate prediction accuracy., Conclusion: We built a useful nomogram model to predict the risk of nephrolithiasis recurrence in patients with PHPT. This would assist clinicians to provide appropriate advices and managements for these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Chu, Jiang, Wu, Xu, Qi, Tang and Dai.)

Introduction: Current guidelines recommend amphotericin B as the preferred drug for induction therapy; however, amphotericin B is not available in certain settings. Induction therapy with amphotericin B deoxycholate or voriconazole has been shown to be an effective treatment for talaromycosis. However, prospective clinical trials comparing these two antifungal drugs are absent from the literature., Methods: In this open-labeled, multicenter, prospective controlled trial, we enrolled patients at 15 hospitals in China from 2019 to 2020. Participants received induction treatment with either amphotericin B deoxycholate intravenously at a dose of 0.5 to 0.7 mg per kilogram per day or voriconazole at a dose of 6 mg/kg intravenously twice daily for the first day, followed by 4 mg/kg intravenously twice daily for 3 days, and then voriconazole was given either intravenously (4 mg/kg intravenously twice daily) or orally (200 mg twice daily) for the remaining 10 days. The primary outcome was all-cause mortality during 48 weeks after baseline. Secondary outcomes were mortality at week 2 or week 24, clinical resolution of talaromycosis, and fungal clearance at week 2. A propensity score (PS) matching analysis was performed to control confounding factors., Results: We observed no difference in the risk of death at week 2, at week 24, or at week 48 in either the unmatched cohort or the matched cohort. Both in the unmatched and the matched cohorts, logistic regression analysis revealed a significantly lower odds ratio of clinical resolution (OR 0.450, 95% CI 0.291-0.696, p < 0.001; OR 0.443, 95% CI 0.261-0.752, p = 0.003) and fungal clearance (OR 0.514, 95% CI 0.333-0.793, p = 0.003; OR 0.542, 95% CI 0.318-0.923, p = 0.024) in voriconazole users compared to amphotericin B deoxycholate users over the course of 2 weeks. In the induction therapy without ART subgroup patients in the amphotericin B deoxycholate group showed a significantly higher rate of clinical resolution and fungal clearance than those in the voriconazole group (56.1% vs. 30.4%, 95% CI 13.4-36.5, p = 0.000; 63.8% vs. 40.4%, 95% CI 11.1-34.7, p = 0.000), whereas there was no significant difference in clinical resolution and fungal clearance in the induction therapy combined with ART subgroup., Conclusions: Induction therapy using voriconazole had a similar efficacy, in terms of all-cause mortality rate, to induction therapy using amphotericin B deoxycholate in HIV-infected patients with talaromycosis over a 48-week observation period. Amphotericin B deoxycholate contributed to earlier fungal clearance and earlier clinical resolution of symptoms in the induction therapy without ART subgroup, whereas amphotericin B deoxycholate use did not contribute to a significant difference in clinical resolution and fungal clearance in the induction therapy combination with ART subgroup., Trial Registration: ChiCTR1900021195. Registered 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 ., (© 2022. The Author(s).)

Reproductive division of labor in the social insects is typically determined by environmental cues; however, genetic effects on caste have been discovered in a growing set of ant taxa. An extreme form of genetic caste determination is "social hybridogenesis," in which co-occurring genetic lineages obligately interbreed to produce workers, whereas daughter queens are of pure-lineage ancestry. In this study, we tested the hypothesis that social hybridogenesis in the genus Pogonomyrmex resulted from one or more interspecific hybridization events, and if so, whether individual lineages were of hybrid ancestry. We reconstructed evolutionary relationships of four lineage pairs to populations of two closely related non-hybridogenetic species, Pogonomyrmex barbatus and Pogonomyrmex rugosus, using nuclear SNP loci and mitochondrial sequencing. The nuclear phylogeny supported a hybridization hypothesis, with one member of each pair nested within P. rugosus, whereas the other was nested within P. barbatus. The source populations corresponded with two distinct geographic areas at the eastern and western edges of a zone of contact. Relatively little gene flow was detected between interbreeding lineages, either historically or currently. This suggests that shifts in reproductive caste determination may reinforce reproductive incompatibility, in a manner similar to the evolution of hybridogenesis in nonsocial systems., (© 2022 The Authors. Evolution © 2022 The Society for the Study of Evolution.)

Background: Testicular germ cell tumours (TGCTs) are the most commonly diagnosed malignancy in young men. Although cisplatin has been shown to be effective to treat TGCT patients, long-term follow-up has shown that TGCT survivors who accepted cisplatin treatment suffered from a greater number of adverse reactions than patients who underwent orchiectomy alone. As metformin has shown an anticancer effect in various cancers, we investigated whether metformin could enhance the effects of cisplatin to treat TGCTs., Methods: The anticancer effects of different treatment strategies consisting of metformin and cisplatin in TCam-2 and NTERA-2 cells were assessed in vitro and in vivo. First, we used a colony formation assay, CCK-8 and MTT assays to explore the viability of TGCT cells. Flow cytometry was used to assess the cell cycle and apoptosis of TGCTs. Then, Western blotting was used to detect the protein expression of TGCTs cells after different treatments. In addition, a xenograft model was used to investigate the effects of the different treatments on the proliferation of TGCT cells. Immunohistochemistry assays were performed to analyse the expression of related proteins in the tissues from the xenograft model., Results: Metformin inhibited the proliferation of TCam-2 and NTERA-2 cells by arresting them in G1 phase, while metformin did not induce apoptosis in TGCT cells. Compared with cisplatin monotherapy, the CCK-8, MTT assay and colony formation assay showed that sequential treatment with metformin and cisplatin produced enhanced anticancer effects. Further study showed that metformin blocked the cells in G1 phase by inducing phosphorylated YAP1 and reducing the expression of cyclin D1, CDK6, CDK4 and RB, which enhanced the chemosensitivity of cisplatin and activated the expression of cleaved caspase 3 in TGCTs., Conclusions: Our study discovers the important role of YAP1 in TGCTs and reports a new treatment strategy that employs the sequential administration of metformin and cisplatin, which can reduce the required cisplatin dose and enhance the sensitivity of TGCT cells to cisplatin. Therefore, this sequential treatment strategy may facilitate the development of basic and clinical research for anticancer therapies to treat TGCTs., (© 2022. The Author(s).)

Objectives: Although antiretroviral therapy (ART) has prolonged the lives of HIV-infected individuals, HIV reservoir remains the main stumbling block to HIV cure. Presently, early ART initiation is one of the effective measures to reduce the HIV reservoir. The effects of ART in Chinese individuals with acute and early HIV infection (AEHI) and chronic HIV infection (CHI) were analyzed in this study., Methods: We performed virological and immunological parameter analysis in 29 AEHI and 19 CHI individuals who were initiated into ART in Beijing, China. The HIV DNA, CD4 + T-cell and CD8 + T-cell counts, and CD4/CD8 ratios between the two groups were compared using statistical analyses., Results: At weeks 48 and 96, the total HIV DNA was significantly lower in the AEHI group than that the CHI group (2.48 [2.26-2.66] vs. 3.06 [2.79-3.33] log10 copies/10 6 peripheral blood mononuclear cells (PBMCs), p < 0.01 at week 48 and 2.17 [1.85-2.45] vs. 2.92 [2.73-3.24] log10 copies/10 6  PBMCs, p < 0.01 at week 96, respectively). The CD4/CD8 T-cell ratio in the AHI group at week 24 was significantly higher than that in the CHI group (0.71 [0.50-0.99] vs. 0.45 [0.34-0.65], p = 0.08). After 48 weeks of ART, there was still a negative correlation between the CD4/CD8 ratio and the HIV DNA level in the CHI group rather than the AEHI group., Conclusions: Early ART initiation could enhance an earlier immunological recovery in AEHI. Immunological normalization after ART initiation could provide important protection against the viral reservoir seeded in AEHI individuals., (© 2022 British HIV Association.)

Objectives: No current academic data is available with respect to the optimal timing to initiate antiretroviral therapy (ART) in HIV-positive patients with talaromycosis. Our study aimed to evaluate the optimal timing of ART initiation for patients presenting with AIDS-related talaromycosis., Methods: In this prospective, randomized, open-label multicenter trial, 228 patients from 15 hospitals in China were randomly assigned to an early ART group (initiation of ART within 2 weeks after randomization) and a deferred ART group (initiation of ART 2 weeks after randomization). The primary endpoint was all-cause mortality during the 48 weeks after randomization., Results: We observed a significant difference in mortality between the early ART group and the deferred ART group (2.2% vs. 8.9%, 95%CI: -0.15 to 14.05, p = 0.049). The composite outcome of AIDS-defining events or death in the early ART group was found to be lower than that in the deferred ART group (3.3% vs. 14.9%; 95%CI: 2.93 to 19.23, p = 0.008)., Conclusions: The prognosis of HIV-infected patients with talaromycosis in the early ART group was more favorable than that of patients in the deferred ART group. These results demonstrate that early ART initiation should be considered in HIV-infected patients with talaromycosis ., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aim: To investigate the short-term dynamic changes and the factors associated with regression of glucose metabolism disorders in patients with hepatitis flare of chronic hepatitis B virus (HBV) infection., Methods: In this study, 118 patients with severe hepatitis flare of chronic HBV infection were prospectively studied. Oral glucose tolerance test was performed on admission and during follow-up to evaluate dynamic changes in glucose metabolism disorders. The factors associated with regression of glucose metabolism disorders were identified using univariate and multivariate logistic regression analyses., Results: The prevalence of diabetes was significantly higher in 70 (47.1%) patients with liver cirrhosis than that in 48 (16.8%) patients without liver cirrhosis. The prevalence of impaired glucose tolerance in patients with liver cirrhosis (35.7%) was significantly lower than that in patients without liver cirrhosis (47.8%). After a follow-up of 20.0 ± 18.7 days, 28 of 31 (90.3%) patients without liver cirrhosis experienced regression of glucose metabolism disorders. Additionally, 30 (54.5%) patients with liver cirrhosis experienced regression of glucose metabolism disorders after 42.0 ± 36.2 days. In patients with liver cirrhosis, those with regression of glucose metabolism disorders had significantly higher levels of homeostasis model assessment-β-cell function, albumin (ALB), and a significantly lower level of fibrosis-4 score. ALB was identified as an independent factor associated with the regression of glucose metabolism disorders in patients with liver cirrhosis., Conclusion: Severe acute liver inflammation aggravates glucose metabolism disorders in patients with hepatitis B-related liver cirrhosis and high ALB level is associated with regression of glucose metabolism disorders upon resolution of acute liver inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Zhu, Liu, Hu, Cheng, Yang, Pei, Zhou, Li and Lin.)

The bilateral cavernous nerve (CN) injury rat model has been extensively used to simulate clinical cavernous nerve injury associated with erectile dysfunction (ED) for evaluating the effect of clinical therapeutic methods. However, the methods of CN injury model construction are flawed and varied in the ED research field. It is CN crush injury that is the most commonly used method in recent years. This study aims to provide a detailed description of the procedure of bilateral CN injury rat model construction and measurement of intracavernous pressure (ICP) recording, providing a reliable and reproducible CN injury rat model. This work successfully developed the CN injury method of hemostat crush injury using a syringe needle as hard support and a hemostat with a rubber sleeve. Also, this method concludes that a voltage of 1.0 V, frequency of 20 Hz, and pulse-width of 5 ms are the optimized stimulation parameters for ICP recording in a bilateral CN injury rat model.

Objective: The association between indoor air pollution resulting from household solid fuel use for heating and cooking with hypertension or blood pressure (BP) remains less clear. This study aims to rectify these knowledge gaps in a large Chinese population., Methods: During 2005-2009, 44 007 individuals aged 35-70 years with complete information on household solid fuel use for cooking and heating were recruited from 279 urban and rural communities of 12 centers. Solid fuel referred to charcoal, coal, wood, agriculture crop, animal dung or shrub. Annual concentration of ambient atmospheric particulate matter that have a diameter of less than 2.5 μm for all communities was collected. Generalized linear mixed models using community as the random effect were performed to estimate the association with hypertension prevalence or BP after considering ambient atmospheric particulate matter that have a diameter of less than 2.5 μm and a comprehensive set of potential confounding factors at the individual and household level., Results: A total of 47.6 and 61.2% of participants used household solid fuel for heating and cooking, respectively. Solid fuel use for heating was not associated with an increase in hypertension prevalence (adjusted odds ratio = 1.08, 95% confident interval: 0.98, 1.20) or elevated SBP (0.62 mmHg, 95% confident interval: -0.24, 1.48). No association was found between solid fuel for cooking and hypertension or BP, and no additional risk was observed among participants who had both exposures to solid fuel for heating and cooking compared with those used for heating only., Conclusion: The current large Chinese study revealed a statistically insignificant increase in the association between solid fuel use for heating and hypertension prevalence or BP. As this cross-sectional study has its inherent limitation on causality, findings from this study would have to be confirmed by prospective cohort studies., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People living with HIV (PLWH) are aging worldwide, and different management strategies may be required for older and younger PLWH. However, demographic characteristics, illness distribution, mortality, and independent risk factors in the PLWH population in China are not yet fully understood, especially in patients aged 50 years or older. Methods: We conducted a retrospective analysis of 4445 HIV-positive Chinese inpatients in Chongqing, China. Results: The mortality rate in patients 50 years or older (the older group) was significantly higher than that in those under 50 years (the younger group) ( p < 0.001). In the younger group, independent risk factors for death included: nadir CD4+ T-cell counts <200 cells/μL, not owning medical healthcare insurance, not being on cART, injection drug use, and having one of the following comorbidities: Pneumocystis pneumonia, cryptococcal meningitis, AIDS malignancy, non-AIDS malignancy, and kidney disease. In the older group, independent predictors of death included: being urban residents, nadir CD4+ T-cell counts <200 cells/μL, not being on cART, and having comorbidities such as Pneumocystis pneumonia, hepatitis C, talaromycosis, non-AIDS malignancy, and kidney disease. Conclusions: Demographic characteristics, illness distribution, mortality, and independent risk factors for death in HIV-positive patients differ between the older group and the younger group, indicating that a changing suite of medical and allied support services may be required the for management of older PLWH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Yang, Liu, Lu, Qin, He, Zeng, Harypursat and Chen.)

Background: Although the widespread use of modern antiretroviral therapy (ART) has reduced the incidence of talaromycosis in people living with HIV, mortality remains as high as 20% in this population, even after appropriate antifungal treatment., Objectives: The objective of our study was to develop a risk assessment system for HIV-infected patients with comorbid talaromycosis, in order to provide these patients with appropriate, effective and potentially life-saving interventions at an early stage of their illness., Patients/methods: This was a multicentre, retrospective cohort study conducted in China. We built a predictive model based on data from 11 hospitals, and a validated model using the data of 1 hospital located in an endemic area., Results: Forward stepwise multivariate statistical calculations indicated that age, aspartate aminotransferase/alanine transaminase ratio and albumin levels, and BUN levels were valid, independent predictors of the risk of death in HIV-infected patients with talaromycosis. Our developed and validated risk scoring system is effective for the identification of HIV-infected patients with talaromycosis at high risk of death at hospital admission (p < .001; AUC = 0.860). In our study, our risk prediction model provided functional and robust discrimination in the validation cohort (p < .001; AUC = 0.793)., Conclusion: The prognostic scoring system for mortality assessment developed in the present study is an easy-to-use clinical tool designed to accurately assist clinicians in identifying high-risk patients with talaromycosis., (© 2020 The Authors. Mycoses published by Wiley-VCH GmbH.)

Background: To date, few studies have evaluated the role of peripheral blood T lymphocyte subsets in patients with clear cell renal cell carcinoma (ccRCC). Here we measured the levels of peripheral blood T lymphocyte subsets and evaluated its prognostic value in ccRCC., Methods: Data from 122 patients with RCC from January 2018 to January 2020 were collected. Preoperative peripheral blood T lymphocyte subsets and medical records were analyzed. Kaplan-Meier cures and log rank test were used for analyzing overall survival (OS). Univariate and multivariate survival analyses were underwent by performing the Cox proportional hazards models. Correlations were tested by Pearson's correlation analysis., Results: Of 122 patients, a total of 80 ccRCC patients was enrolled. Patients with low CD3 + T cells and low CD4 + /CD8 + ratio displayed a worse OS than patients with high CD3 + T cells and high CD4 + /CD8 + ratio (P=0.029 and 0.002, respectively). Multivariate analyses showed CD3 + T cells and CD4 + /CD8 + ratio were independent predictive factors for the OS (HR: 0.295, 95% CI, 0.091-0.956; P=0.042 and HR: 0.244, 95% CI, 0.065-0.920; P=0.037, respectively). Moreover, NLR negatively correlated with both levels of CD3 + T cells and CD4 + /CD8 + ratio (P<0.001, r=-0.398 and P=0.012, r=-0.280, respectively)., Conclusions: The findings of our study suggest that preoperative CD3 + T cells and CD4 + /CD8 + ratio in peripheral blood are independent predictors for patients with ccRCC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-1066). The authors have no other conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

Purpose: To determine whether hypertriglyceridemic waist (HTGW) and high lipid accumulation product (LAP) preceded the incidence of type 2 diabetes mellitus (T2DM), and to investigate the interactions of HTGW and LAP with other components of metabolic syndrome on the risk of T2DM., Methods: A total of 15,717 eligible participants without baseline T2DM and aged 35 and over were included from a Chinese rural cohort. Cox proportional hazards regression models were used to estimate the association of HTGW and LAP with the incidence of T2DM, and the restricted cubic spline model was used to evaluate the dose-response association., Results: Overall, 867 new T2DM cases were diagnosed after 7.77 years of follow-up. Participants with HTGW had a higher hazard ratio for T2DM (hazard ratio (HR): 6.249, 95% confidence interval (CI): 5.199-7.511) after adjustment for potential confounders. The risk of incident T2DM was increased with quartiles 3 and 4 versus quartile 1 of LAP, and the adjusted HRs (95% CIs) were 2.903 (2.226-3.784) and 6.298 (4.911-8.077), respectively. There were additive interactions of HTGW (synergy index (SI): 1.678, 95% CI: 1.358-2.072) and high LAP (SI: 1.701, 95% CI: 1.406-2.059) with increased fasting plasma glucose (FPG) on the risk of T2DM. Additionally, a nonlinear ( P nonlinear < 0.001) dose-response association was found between LAP and T2DM., Conclusion: The subjects with HTGW and high LAP were at high risk of developing T2DM, and the association between LAP and the risk of T2DM may be nonlinear. Our study further demonstrates additive interactions of HTGW and high LAP with increased FPG on the risk of T2DM., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2020 Minrui Xu et al.)

The human neurotropic virus JC Polyomavirus, a member of the Polyomaviridae family, is the opportunistic infectious agent causing progressive multifocal leukoencephalopathy, typically in immunocompromised individuals. The spectrum of underlying reasons for the systemic immunosuppression that permits JCV infection in the central nervous system has evolved over the past 2 decades, and therapeutic immunosuppression arousing JCV infection in the brain has become increasingly prominent as a trigger for PML. Effective immune restoration subsequent to human immunodeficiency virus-related suppression is now recognized as a cause for unexpected deterioration of symptoms in patients with PML, secondary to a rebound inflammatory phenomenon called immune reconstitution inflammatory syndrome, resulting in significantly increased morbidity and mortality in a disease already infamous for its lethality. This review addresses current knowledge regarding JC Polyomavirus, progressive multifocal leukoencephalopathy, progressive multifocal leukoencephalopathy-related immune reconstitution inflammatory syndrome, and the immunocompromised states that incite JC Polyomavirus central nervous system infection, and discusses prospects for the future management of these conditions.

Background: Pneumocystis pneumonia (PCP) is a common acquired immune deficiency syndrome (AIDS)-related opportunistic infection. Recent reports estimate that more than 400,000 patients with human immunodeficiency virus (HIV) develop PCP each year globally. However, the timing of antiretroviral therapy (ART) initiation for HIV-infected patients with PCP is still controversial, and the benefits and risks of early initiation of ART are not completely clear. We thus designed this study in order to determine the optimal timing for ART initiation for HIV-positive patients with moderate to severe PCP., Methods: This study will be an open-label, multi-centre, prospective randomised controlled trial. A total of 200 subjects will be randomly assigned to an early ART initiation group (≤14 days after PCP diagnosis) and a deferred ART initiation group (>14 days after PCP diagnosis) at a 1:1 ratio. All subjects will be followed up for 48 weeks after starting ART. The primary endpoint is incidence of disease progression (including new or relapsing opportunistic infections and death) at week 48. The secondary endpoints are the changes in CD4 counts from baseline at weeks 12, 24 and 48; the degree of virological suppression (HIV RNA < 50 copies/mL) at weeks 24 and 48; the rate of development of PCP-associated immune reconstitution inflammatory syndrome; and adverse events over 48 weeks., Discussion: We hope that the results of this study will reveal the optimal timing for initiation of ART in HIV-infected patients with moderate to severe PCP., Trial Registration: This trial was registered as one of the 12 trials under the name of a general project at chictr.org.cn on February 1, 2019. The registration number of the general project is ChiCTR1900021195.

With the global climate change and the rapid urbanization process, there is an increase in the risk of urban floods. Therefore, undertaking risk studies of urban floods, especially the depth prediction of urban flood is very important for urban flood control. In this study, an urban flood data warehouse was established with available structured and unstructured urban flood data. In this study, an urban flood data warehouse was established with available structured and unstructured urban flood data. Based on this, a regression model to predict the depth of urban flooded areas was constructed with deep learning algorithm, named Gradient Boosting Decision Tree (GBDT). The flood condition factors used in modeling were rainfall, rainfall duration, peak rainfall, evaporation, land use (the proportion of roads, woodlands, grasslands, water bodies and building), permeability, catchment area, and slope. Based on the rainfall data of different rainfall return periods, flood condition maps were produced using GIS. In addition, the feature importance of these conditioning factors was determined based on the regression model. The results demonstrated that the growth rate of the number and depth of the water accumulation points increased significantly after the rainfall return period of 'once in every two years' in Zhengzhou City, and the flooded areas mainly occurred in the old urban areas and parts of southern Zhengzhou. The relative error of prediction results was 11.52%, which verifies the applicability and validity of the method in the depth prediction of urban floods. The results of this study can provide a scientific basis for urban flood control and drainage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Tenofovir disoproxil fumarate (TDF) can cause renal and bone toxicity, which is associated with high plasma tenofovir concentrations in antiretroviral treatment of HIV-1 infected patients. Tenofovir alafenamide (TAF) is a novel tenofovir prodrug with a 90% reduction in plasma tenofovir concentrations. We aimed to assess the non-inferiority of a TAF-containing combination regimen versus a TDF-containing fixed-dose single-tablet regimen in the antiretroviral-treatment-naive, HIV-1-infected patients., Methods: We searched PubMed, Embase, Web of Science, and the Cochrane Trial Registry, from January 2001 to July 2019, using relevant keywords. Available data were extracted from eligible randomized trials (RCTs) and pooled as risk ratios (RRs) or standardized mean differences (SMDs) in a meta-analysis model using Stata/SE., Results: We included seven eligible randomized controlled trials (RCTs) with a total of 6269 participants. Patients who were antiretroviral-naive adults with HIV-1 on both the TAF-containing regimens and the TDF-containing regimens had similar virologic suppression effects (RR, 1.02; 95% CI, 1.00-1.04; p > 0.05) at week 24 (93.99% vs. 94.20%), week 48 (90.71% vs. 89.54%), and week 96 (86.16% vs. 84.80%). Both groups had no significant improvements in CD4 cell count for the naive patients during 48 weeks of therapy (SMD, 0.09; 95% CI, 0.01 to 0.16; p < 0.05). Both treatments were safe and well-tolerated, and most adverse events were similar as mild to moderate in severity. Moreover, compared with the TDF-containing regimens, the TAF-containing regimens in patients had significantly smaller reductions in both hip (RR, 0.33; 95CI, 0.29-0.39; p < 0.05) and spine (RR, 0.58; 95CI, 0.51-0.65; p < 0.05). Additionally, the TAF-containing regimens in patients had significantly fewer increases for renal events than those of the TDF-containing regimens through 48 weeks (0.31; 95% CI, 0.18-0.55; p < 0.05)., Conclusions: Our meta-analysis indicated that efficacy, safety, and tolerability of TAF-containing regimens were non-inferior in fixed-dose single-tablet regimens for initial treatment of HIV-1 infection. Furthermore, compared with those receiving the TDF-containing regimens, patients on the TAF-containing regimens had significant advantages in renal function, bone parameters, and lipid profile for the naive patients., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Adenosine A2b receptor (A2bR) is a member of the G protein-coupled receptor superfamily members, which has been considered involved in the pathogenesis of various cancers. However, little is known about the role of A2bR renal cell carcinoma (RCC). The A2bR expression levels in RCC 769-P and Caki-1 cell lines compared with HK-2 were analyzed by qRT-PCR. 769-P and Caki-1 cells were transfected with shRNA-A2bR to knock down the expression of A2bR. Cell proliferation was detected by MTT assays and colony formation assays. Wounding healing assays and transwell assays were used to evaluate the effects of A2bR on cell capacity of invasion and migration. Finally, potential mechanisms involved in A2bR blockade's effects on altered tumor behaviors were evaluated by western blotting. We showed that A2bR were significantly up-regulated in RCC cells compared to HK-2 cell. Functionally, MRS1754, a selective A2bR antagonist, and knocking-down the expression of A2bR by shRNA reduced proliferation and migration in vitro and tumor growth in vivo . Furthermore, we demonstrated that A2bR blockade inhibited tumor progression in part via the MAPK/JNK pathway. Conclusion : Our findings suggest the A2bR potentially plays an important role in RCC progression and A2bR blockade may be a promising candidate for therapeutic intervention for renal cell carcinoma., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: To investigate whether TDF-containing regimens significantly benefited efficacy, safety, and tolerability in TAF-containing regimens in virologically suppressed HIV-infected patients., Methods: PubMed, Embase, Web of Science, and the Cochrane Trial Registry were systematically searched for eligible studies. We extracted and evaluated the pooled data from available randomized controlled trials (RCTs)., Results: Eight eligible RCTs were included. In the intention-to-treat (ITT) analysis, patients who switched to TAF-containing regimens had significantly better viral suppression than those continuing TDF-containing regimens at weeks 48 and 96 (RR, 1.02; 95CI, 1.00-1.03; p<0.05), but no significant difference in the per-protocol (PP) analysis (RR, 1.00; 95CI, 0.99-1.01; p>0.05). Compared with those receiving the TDF-containing regimens, virologically suppressed HIV-infected patients on the TAF-containing regimens had significant increases in CD4 cell counts (SMD, 0.12; 95CI, 0.08 to 0.17; p<0.05), renal and bone parameters at the hip (RR, 2.86; 95CI, 2.24-3.64; p<0.05) and the spine (RR, 2.43; 95 CI, 2.03-2.90; p<0.05) between weeks 48 and 96., Conclusions: Virologically suppressed HIV-infected patients on TDF-containing regimens significantly benefit from switching to TAF-containing regimens, resulting in better viral suppression, better immune reconstruction, and less bone and renal problems., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Specific characteristics of the male Achroia grisella acoustic mating signal determine a male's attractiveness toward females. These features are genetically variable in populations, and mapping experiments have been used to identify loci contributing to song variation, and understand the evolutionary forces acting on this important sexual trait. Here we built on this foundation and carried out QTL (Quantitative Trait Locus) mapping using >1,000 recombinant individuals, genotyping this large cohort at thousands of sequence-based markers covering the entire collection of 30 A. grisella chromosomes. This dense marker set, coupled with our development of an annotated, draft genome of A. grisella , allowed us to link >3,000 genome scaffolds, >10,000 predicted genes, and close to 275Mb of genome sequence to chromosomes. Our QTL mapping confirmed a fraction of the QTL identified in a previous study, and additionally revealed novel loci. Collectively, QTL explained only small fractions of the phenotypic variance, suggesting many more causative factors remain below the detection threshold of our study. A surprising, and ultimately challenging feature of our study was the low level of intrachromosomal recombination present in our mapping population. This led to difficulty ordering markers along linkage groups, necessitating a chromosome-by-chromosome mapping approach, rather than true interval mapping, and precluded confident ordering/orienting of scaffolds along each chromosome. Nonetheless, our study increased the genomic resources available for the A. grisella system. Enabled by ever more powerful technologies, future investigators will be able to leverage our data to provide more detailed genetic dissection of male song variation in A. grisella ., (Copyright © 2019 Koseva et al.)

Bladder urothelial carcinoma (BUC) is one of the most common urological malignancies. Our previous study found that adenosine A2b receptor (A2bR) was upregulated in BUC tissues and cells. In the present study, we investigated the effect of MRS1754 (a selective A2bR antagonist) on cell proliferation and migration in two well-studied invasive urothelial cell carcinoma lines EJ and T24. Our results showed that MRS1754 reduced BUC cell proliferation and induced a G0/G1 phase cell-cycle arrest. Next, MRS1754 inhibited cell migration and Bay60-6583 (a selective A2bR agonist) treatment could reverse the inhibitory effect of MRS1754 on BUC cells migration. Furthermore, our results showed MRS1754 treatment downregulated the protein levels of p-P38, p-JNK, and phospho-extracellular signal-regulated kinase (p-ERK). These findings suggest that MRS1754 can inhibit progression of BUC via mitogen-activated protein kinase (MAPK) pathway and indicate the therapeutic potential of A2B antagonists in BUC., (© 2018 Wiley Periodicals, Inc.)

Pim kinases are a family of constitutively active serine/threonine kinases that are partially redundant and regulate multiple pathways important for cell growth and survival. In human disease, high expression of the three Pim isoforms has been implicated in the progression of hematopoietic and solid tumor cancers, which suggests that Pim kinase inhibitors could provide patients with therapeutic benefit. Herein, we describe the structure-guided optimization of a series of quinazolinone-pyrrolodihydropyrrolone analogs leading to the identification of potent pan-Pim inhibitor 28 with improved potency, solubility, and drug-like properties. Compound 28 demonstrated on-target Pim activity in an in vivo pharmacodynamic assay with significant inhibition of BAD phosphorylation in KMS-12-BM multiple myeloma tumors for 16 h postdose. In a 2-week mouse xenograft model, daily dosing of compound 28 resulted in 33% tumor regression at 100 mg/kg.

Anopheles gambiae devotes over 2% of its protein coding genes to its 298 structural cuticular proteins (CPs). This paper provides new LC-MS/MS data on two adult structures, proboscises and palps, as well as three larval samples - 4th instar larvae, just their terminal segment, and a preparation enriched in their tracheae. These data were combined with our previously published results of proteins from five other adult structures, whole adults, and two preparations chosen for their relatively clean cuticle, the larval head capsules left behind after ecdysis and the pupal cuticles left behind after adult eclosion. Peptides from 28 CPs were recovered in all adult structures; 24 CPs were identified for the first time, 6 of these were members of the TWDL family. Most newly identified proteins came from the larval sources. Based solely on peptide recovery, from our data and from other investigators, most available on VectorBase, there were only 4 CPs that were restricted to a single adult structure. More were restricted to a single metamorphic stage, 14 in larvae, 0 in pupae and 32 in adults. Expression data from our earlier RT-qPCR studies reduces these numbers. Charting restriction of CPs to stage or structure is a step forward in establishing their specific roles., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Data are scarce on the availability and affordability of essential medicines for diabetes. Our aim was to examine the availability and affordability of metformin, sulfonylureas, and insulin across multiple regions of the world and explore the effect of these on medicine use., Methods: In the Prospective Urban Rural Epidemiology (PURE) study, participants aged 35-70 years (n=156 625) were recruited from 110 803 households, in 604 communities and 22 countries; availability (presence of any dose of medication in the pharmacy on the day of audit) and medicine cost data were collected from pharmacies with the Environmental Profile of a Community's Health audit tool. Our primary analysis was to describe the availability and affordability of metformin and insulin and also commonly used and prescribed combinations of two medicines for diabetes management (two oral drugs, metformin plus a sulphonylurea [either glibenclamide (also known as glyburide) or gliclazide] and one oral drug plus insulin [metformin plus insulin]). Medicines were defined as affordable if the cost of medicines was less than 20% of capacity-to-pay (the household income minus food expenditure). Our analyses included data collected in pharmacies and data from representative samples of households. Data on availability were ascertained during the pharmacy audit, as were data on cost of medications. These cost data were used to estimate the cost of a month's supply of essential medicines for diabetes. We estimated affordability of medicines using income data from household surveys., Findings: Metformin was available in 113 (100%) of 113 pharmacies from high-income countries, 112 (88·2%) of 127 pharmacies in upper-middle-income countries, 179 (86·1%) of 208 pharmacies in lower-middle-income countries, 44 (64·7%) of 68 pharmacies in low-income countries (excluding India), and 88 (100%) of 88 pharmacies in India. Insulin was available in 106 (93·8%) pharmacies in high-income countries, 51 (40·2%) pharmacies in upper-middle-income countries, 61 (29·3%) pharmacies in lower-middle-income countries, seven (10·3%) pharmacies in lower-income countries, and 67 (76·1%) of 88 pharmacies in India. We estimated 0·7% of households in high-income countries and 26·9% of households in low-income countries could not afford metformin and 2·8% of households in high-income countries and 63·0% of households in low-income countries could not afford insulin. Among the 13 569 (8·6% of PURE participants) that reported a diagnosis of diabetes, 1222 (74·0%) participants reported diabetes medicine use in high-income countries compared with 143 (29·6%) participants in low-income countries. In multilevel models, availability and affordability were significantly associated with use of diabetes medicines., Interpretation: Availability and affordability of essential diabetes medicines are poor in low-income and middle-income countries. Awareness of these global differences might importantly drive change in access for patients with diabetes., Funding: Full funding sources listed at the end of the paper (see Acknowledgments)., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs (NNRTIs) with boosted protease inhibitors are included in standardized first-line and second-line regimens. Recent World Health Organization (WHO) guidelines recommend a boosted protease inhibitor (PI) combined with 2 NRTIs or raltegravir as a second-line regimen. Objective: Ritonavir-boosted lopinavir (LPV/r) is known as a key second-line antiretroviral therapy (ART) in resource-limited settings. We carried out a meta-analysis to analyze virologic suppression and effectiveness of LPV/r-based second-line therapy in HIV-infected patients. Methods: In this meta-analysis, we searched randomized controlled trials and observational cohort studies to evaluate outcomes of second-line ART for patients with HIV who failed first-line therapy. A systematic search was conducted in Pubmed, Cochrane Library, and Embase from inception to January 2018. Outcomes included viral suppression, CD4 cell counts, drug resistance, adverse events, and self-reported adherence. We assessed comparative efficacy and safety in a meta-analysis. Data analysis was performed using RevMan 5.3 and Stata12.0. Results: Nine studies comprising 3,923 patients were included in the meta-analysis. The overall successful virologic suppression rate of the second-line regimen was 77% (ITT) and 87% (PP) at 48 weeks with a plasma HIV RNA load of <400 copies/mL. No statistical significance was found in CD4 cell count recoveries between LPV/r plus 2-3 NRTIs and simplified regimens (LPV/r plus raltegravir) at 48 weeks ( P = 0.09), 96 weeks ( P = 0.05), and 144 weeks ( P = 0.73). Four studies indicated that the virus had low-level resistance to LPV/r, and the most common clinically significant PI-resistance mutations were 46I, 54V, 82A/82F, and 76V; however, no virologic failure due to LPV/r resistance was detected. In addition, no statistical significance was found between the two groups in self-reported adherence [relative risks (RR) = 1.03,95% confidence interval (CI) 1.00, 1.07, P = 0.06], grade 3 or 4 adverse events (RR = 0.84, 95% CI 0.64, 1.10, P = 0.20) or serious events (RR = 0.85, 95% CI 0.77, 1.17, P = 0.62). Conclusions: These results suggest that the LPV/r-based regimen demonstrates efficacious and low resistance as second-line antiretroviral therapy.Both LPV/r plus 2-3 NRTIs and LPV/r plus RAL regimens improved CD4 cell counts. There was no evidence of superiority of simplified regimens over LPV/r plus 2-3 NRTIs.

The adenosine A2b receptor (A2bR) was considered to play an oncogenic role in many human malignancies. However, the expression and molecular function of A2bR in bladder urothelial carcinoma (BUC) have not been well elucidated. Herein, we found that the expression of A2bR was higher than other adenosine receptors in BUC tissues and cells, and it was upregulated in BUC tissues compared with matched normal bladder tissues. Furthermore, high expression of A2bR was associated with poor prognosis of patients with BUC. In addition, suppression of A2bR inhibited the proliferation, migration and invasion of BUC cells and arrested the cell cycle at the G1 phase. Finally, we demonstrated that downregulation of A2bR inhibited the proliferation, migration and invasion of BUC in part via the MAPK signaling pathway, increasing the levels of P21 but decreasing the levels of cyclin B1, D, E1, MMP-2 and MMP-9. Overexpression of MMP-2 could rescue BUC cells migration and invasion. Thus, the present study indicates that A2bR may play a potential oncogenic role in BUC progression and act as a potential biomarker to identify BUC patients with poor clinical outcomes.

Aims: Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat., Materials and Methods: Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant., Results: Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05). Progressive allograft fibrosis as well as collagen deposition were observed., Conclusions: These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.