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STUDY QUESTION Can whole-exome sequencing (WES) reveal new genetic factors responsible for male infertility characterized by oligozoospermia? SUMMARY ANSWER We identified biallelic missense variants in the Potassium Channel Tetramerization Domain Containing 19 gene (KCTD19) and confirmed it to be a novel pathogenic gene for male infertility. WHAT IS KNOWN ALREADY KCTD19 is a key transcriptional regulator that plays an indispensable role in male fertility by regulating meiotic progression. Kctd19 gene-disrupted male mice exhibit infertility due to meiotic arrest. STUDY DESIGN, SIZE, DURATION We recruited a cohort of 536 individuals with idiopathic oligozoospermia from 2014 to 2022 and focused on five infertile males from three unrelated families. Semen analysis data and ICSI outcomes were collected. WES and homozygosity mapping were performed to identify potential pathogenic variants. The pathogenicity of the identified variants was investigated in silico and in vitro. PARTICIPANTS/MATERIALS, SETTING, METHODS Male patients diagnosed with primary infertility were recruited from the Reproductive and Genetic Hospital of CITIC-Xiangya. Genomic DNA extracted from affected individuals was used for WES and Sanger sequencing. Sperm phenotype, sperm nuclear maturity, chromosome aneuploidy, and sperm ultrastructure were assessed using hematoxylin and eosin staining and toluidine blue staining, FISH and transmission electron microscopy. The functional effects of the identified variants in HEK293T cells were investigated via western blotting and immunofluorescence. MAIN RESULTS AND THE ROLE OF CHANCE We identified three homozygous missense variants (NM_001100915, c.G628A:p.E210K, c.C893T:p.P298L, and c.G2309A:p.G770D) in KCTD19 in five infertile males from three unrelated families. Abnormal morphology of the sperm heads with immature nuclei and/or nuclear aneuploidy were frequently observed in individuals with biallelic KCTD19 variants, and ICSI was unable to rescue these deficiencies. These variants reduced the abundance of KCTD19 due to increased ubiquitination and impaired its nuclear colocalization with its functional partner, zinc finger protein 541 (ZFP541), in HEK293T cells. LIMITATIONS, REASONS FOR CAUTION The exact pathogenic mechanism remains unclear, and warrants further studies using knock-in mice that mimic the missense mutations found in individuals with biallelic KCTD19 variants. WIDER IMPLICATIONS OF THE FINDINGS Our study is the first to report a likely causal relationship between KCTD19 deficiency and male infertility, confirming the critical role of KCTD19 in human reproduction. Additionally, this study provided evidence for the poor ICSI clinical outcomes in individuals with biallelic KCTD19 variants, which may guide clinical treatment strategies. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the National Key Research and Developmental Program of China (2022YFC2702604 to Y.-Q.T.), the National Natural Science Foundation of China (81971447 and 82171608 to Y.-Q.T., 82101961 to C.T.), a key grant from the Prevention and Treatment of Birth Defects from Hunan Province (2019SK1012 to Y.-Q.T.), a Hunan Provincial Grant for Innovative Province Construction (2019SK4012), and the China Postdoctoral Science Foundation (2022M721124 to W.W.). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER N/A.

Objective Our previous studies showed that renal medullary sphingosine-1-phosphate receptor 1 (S1PR1) mediated sodium excretion, high salt intake increased S1PR1 level, deoxycorticosterone acetate (DOCA) blocked high salt-induced S1PR1 in the renal medulla, and that conditional knockout of S1PR1 in the collecting duct aggravated DOCA-salt hypertension. The present study tested the hypothesis that overexpression of S1PR1 transgene in the renal medulla attenuates the sodium retention and hypertension in DOCA-salt mouse model. Methods Male C57BL/6J mice received renal medullary transfection of control or S1PR1-expressing plasmids and then DOCA-salt treatment. Renal sodium excretion and arterial pressure were compared between control and S1PR1-overexpressed mice in response to high salt loading or pressure natriuresis. Results S1PR1-transfected mice showed significantly enhanced urinary sodium excretion in response to acute sodium loading (0.93±0.27 in control vs. 4.72±1.12 µmol/min/gKW in S1PR1-overexpressed mice, p Conclusion These results suggested that activation of S1PR1 in the renal medulla attenuates DOCA-induced sodium retention and salt-sensitive hypertension associated with inhibition of ENaC.

Fatty acid amide hydrolase (FAAH) is the primary enzyme that degrades the endocannabinoid anandamide (AEA). Inhibition of FAAH by pharmacology or genetic approach has been shown to reduce inflammation in the brain, colon, heart and kidneys. Kidney medullary infusion of a FAAH inhibitor exerts diuretic and natriuretic effects. Faah knockout mice are protected from both post ischemia reperfusion injury and cisplatin-induced acute kidney injury (AKI) but through distinct mechanisms. The presented study tested the hypothesis that pharmacological inhibition of FAAH activity mitigates cisplatin-induced AKI and explored the potential renoprotective mechanism. Male wild type C57BL/6 (WT) were treated with oral gavage of a FAAH inhibitor (PF-04457845, PF, 5mg/kg) or vehicle (10% PEG200+5% Tween80+normal saline) at 72, 48, 24, 2-hr before and 24, 48-hr after a single dose of intraperitoneal injection of cisplatin (Cis, 25 mg/kg). Mice were euthanatized 72 hours after cisplatin treatment. PF-treated mice showed a decrease of cisplatin-induced plasma creatinine levels compared with vehicle (Veh)-treated mice (mean: 0.23±0.17, 1.98± 1.09, 0.31±0.16 and 1.11±0.56 mg/dL in Veh, Veh+Cis, PF and PF+Cis, respectively, p=0.02). Western blot analysis revealed that increased kidney injury molecule-1 (KIM-1) levels in kidney tissue of Veh-mice by cisplatin were reduced in PF-treated mice (2-fold increase vs. 1.1-fold in Veh+Cis vs. PF+Cis compared to the Veh-mice, respectively, p=0.04). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay showed that PF+Cis mice displayed enhanced AEA tone compared with Veh+Cis mice (1.3-fold increase vs. 2.9-fold in Veh+Cis vs. PF+Cis compared to the Veh-mice, respectively, p=0.03). These results suggest that the renal protection from oral gavage of the FAAH inhibitor against cisplatin nephrotoxicity may be associated with enhanced tone of AEA and that pharmacological inactivation of FAAH could be a novel strategy to prevent cisplatin-induced AKI. NIH grant R01HL145163 and P30DA033934 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Primary screening daat from kinome siRNA screen

Human papillomavirus (HPV) is the causative agent in cervical cancer. HPV oncogenes are major drivers of the transformed phenotype, and the cancers remain addicted to these oncogenes. A screen of the human kinome has identified inhibition of Aurora kinase A (AURKA) as being synthetically lethal on the background of HPV E7 expression. The investigational AURKA inhibitor MLN8237/Alisertib selectively promoted apoptosis in the HPV cancers. The apoptosis was driven by an extended mitotic delay in the Alisertib-treated HPV E7–expressing cells. This had the effect of reducing Mcl-1 levels, which is destabilized in mitosis, and increasing BIM levels, normally destabilized by Aurora A in mitosis. Overexpression of Mcl-1 reduced sensitivity to the drug. The level of HPV E7 expression influenced the extent of Alisertib-induced mitotic delay and Mcl-1 reduction. Xenograft experiments with three cervical cancer cell lines showed Alisertib inhibited growth of HPV and non-HPV xenografts during treatment. Growth of non-HPV tumors was delayed, but in two separate HPV cancer cell lines, regression with no resumption of growth was detected, even at 50 days after treatment. A transgenic model of premalignant disease driven solely by HPV E7 also demonstrated sensitivity to drug treatment. Here, we show for the first time that targeting of the Aurora A kinase in mice using drugs such as Alisertib results in a curative sterilizing therapy that may be useful in treating HPV-driven cancers. Mol Cancer Ther; 14(12); 2753–61. ©2015 AACR.

SiRNA screening data validated gene lists

Contains siRNA primary screen analysis and subsequent supplemental analyses; Figure S1 Analysis was performed using customized R scripts and proceeded via a three step process; Figure S2 Summary of Z scores of the top 54 selected target hits from the primary screen were rescreened using OnTarget Plus siRNAs; Figure S3 Mitosis is not a general target in HPV-transformed cancer cell lines; Figure S4A. Dose response for all the cell lines with the Aurora B inhibitor ZM447439; Figure S4B. Flow cytometry of the DNA content of cells were treated with 5 μM ZM447439 and collected at 24, 48, and 72 h, using DMSO as a control; Figure S5: Either wild type or K14E7 transgenic skin grafted onto wild type mice, either treated with Alisertib in vivo or untreated, was stained for mast cells using touluidine blue; Figure S6: Alisertib treatment of HPV-transformed cancer cells promotes apoptosis; Figure S7A. HPV- and non-HPV-transformed cancer cells were treated with 5 μM Alisertib and sampled at intervals over 72 h and analysed by flow cytometry for DNA content; S7B. Immunofluorescence of representative HPV-transformed (HeLa) and non-HPV C33A cells treated with DMSO (Control) or 5μM of Alisertib for 48 h stained for DNA and microtubules (α-tubulin). S7C. Quantitation of bi-nucleated and multinucleated cells in control and Alisertibtreated cells for 1 and 2 days; Figure S8 Representative time-lapse series of HeLa and C33A with and without 5 μM Alisertib treatment transiting mitosis and undergoing apoptosis; Figure S9: The time lines for 50 HeLa and 50 CaSki cells treated with 5 μM Alisertib; Figure S10: The dose response of parental HeLa cells and HeLa cells over expressing either Bcl-2 or Mcl- 1 with etoposide and Taxol, respectively, are shown; Figure S11: HPV-transformed ME180 and non-HPV C33A cells were treated with 5 μM Alisertib for up to 3 days; Figure S12 Dose response curves for HPV16 E7 expressing C33A and SCC25 cell lines determined (one of four replicate experiments); Figure S13: FACS of the GFP levels in the HPV18 E7-IRES-GFP transduced SCC25 cell lines used in Figure 7B, C.

Purpose:We recently reported that indoleamine 2, 3-dioxygenase (IDO) activity is significantly correlated with more distant metastasis and worse survival. The present study examined whether radiotherapy (RT) dose fractionation correlates with IDO-mediated immune activity in patients with early-stage NSCLC.Methods: Patients with newly diagnosed stage I-II NSCLC treated with either conventionally fractionated 3-dimensional conformal radiotherapy (3DCRT) or stereotactic body radiotherapy (SBRT) were analyzed. Levels of two key molecules associated with the IDO immune checkpoint, serum kynurenine and the kynurenine:tryptophan ratio (K:T ratio), were measured at pre-RT, during-RT, and 3-month post-RT. The relationship between disease control outcomes [overall survival (OS), progression free survival, and local/regional/distant failure rates] and absolute levels of these markers, as well as dynamic changes in their levels during RT, was studied.Results:Fifty-six patients (SBRT = 28, 3DCRT = 28) with early-stage NSCLC were studied. In all patients, higher kynurenine post-RT was significantly associated with worse OS ([HR, 1.25; 95% confidence interval (CI), 1.01–1.55; P = 0.044). No statistically significant differences in absolute kynurenine levels or the K:T ratio were observed in patients treated with 3DCRT or SBRT at any of the three time points. However, the absolute kynurenine levels rose significantly more post-RT in the 3DCRT patients with a median increase 0.721 ng/mL, compared to that of SBRT patients (0.115 ng/mL); P = 0.022.Conclusions:This study validated that elevated IDO activity correlated with worse survival outcomes in patients with early-stage NSCLC treated with definitive RT. Hypofractionated SBRT may have less immunosuppressive effect than 3DCRT, as measured by IDO.

Figure S3. Ectopic miR-204-5p expression increases the sensitivity of CRC cells to 5-FU and DDP. A, and B, miR-204 overexpression enhanced 5-FU and DDP-induced apoptosis in LoVo (A) and HCT116 (B) cells. Annexin V/PI staining and FACs analysis were performed to detect apoptosis of LoVo and HCT116 cells after administration of 5 μg/mL 5-FU and DDP. The apoptosis levels were determined by the Annexin V positive ratio.

prediction abilities in the previous reports

Purpose:Radiation pneumonitis is an important adverse event in patients with non–small cell lung cancer (NSCLC) receiving thoracic radiotherapy. However, the risk of radiation pneumonitis grade ≥ 2 (RP2) has not been well predicted. This study hypothesized that inflammatory cytokines or the dynamic changes during radiotherapy can improve predictive accuracy for RP2.Experimental Design:Levels of 30 inflammatory cytokines and clinical information in patients with stages I–III NSCLC treated with radiotherapy were from our prospective studies. Statistical analysis was used to select predictive cytokine candidates and clinical covariates for adjustment. Machine learning algorithm was used to develop the generalized linear model for predicting risk RP2.Results:A total of 131 patients were eligible and 17 (13.0%) developed RP2. IL8 and CCL2 had significantly (Bonferroni) lower expression levels in patients with RP2 than without RP2. But none of the changes in cytokine levels during radiotherapy was significantly associated with RP2. The final predictive GLM model for RP2 was established, including IL8 and CCL2 at baseline level and two clinical variables. Nomogram was constructed based on the GLM model. The model's predicting ability was validated in the completely independent test set (AUC = 0.863, accuracy = 80.0%, sensitivity = 100%, specificity = 76.5%).Conclusions:By machine learning, this study has developed and validated a comprehensive model integrating inflammatory cytokines with clinical variables to predict RP2 before radiotherapy that provides an opportunity to guide clinicians.

Supplementary Legend

Table S1 and Figure S1

Table S3. Downregulated transcripts in miR-204-5p transfected HCT116 cells

Detail of Prospective Clinical Trials.

Purpose: miR-204-5p was found to be downregulated in colorectal cancer tissues in our preliminary microarray analyses. However, the function of miR-204-5p in colorectal cancer remains unknown. We therefore investigated the role, mechanism, and clinical significance of miR-204-5p in colorectal cancer development and progression.Experimental Design: We measured the expression of miR-204-5p and determined its correlation with patient prognoses. Ectopic expression in colorectal cancer cells, xenografts, and pulmonary metastasis models was used to evaluate the effects of miR-204-5p on proliferation, migration, and chemotherapy sensitivity. Luciferase assay and Western blotting were performed to validate the potential targets of miR-204-5p after the preliminary screening by a microarray analysis and computer-aided algorithms.Results: miR-204-5p is frequently downregulated in colorectal cancer tissues, and survival analysis showed that the downregulation of miR-204-5p in colorectal cancer was associated with poor prognoses. Ectopic miR-204-5p expression repressed colorectal cancer cell growth both in vitro and in vivo. Moreover, restoring miR-204-5p expression inhibited colorectal cancer migration and invasion and promoted tumor sensitivity to chemotherapy. Mechanistic investigations revealed that RAB22A, a member of the RAS oncogene family, is a direct functional target of miR-204-5p in colorectal cancer. Furthermore, RAB22A protein levels in colorectal cancer tissues were frequently increased and negatively associated with miR-204-5p levels and survival time.Conclusions: Our results demonstrate for the first time that miR-204-5p acts as a tumor suppressor in colorectal cancer through inhibiting RAB22A and reveal RAB22A to be a new oncogene and prognostic factor for colorectal cancer. Clin Cancer Res; 20(23); 6187–99. ©2014 AACR.

Supplementary Table S1. Patients' information Supplementary Table S2. Primer sequences Supplementary Figure Legends

The small molecular second near-infrared (NIR-II, 1000-1700 nm) dye-based nanotheranostics can concurrently combine deep-tissue photodiagnosis with in situ phototherapy, which occupies a vital position in the early detection and precise treatment of tumors. However, the development of small molecular NIR-II dyes is still challenging due to the limited electron acceptors and cumbersome synthetic routes. Herein, we report a novel molecular electron acceptor, boron difluoride formazanate (BDF). Based on BDF, a new small molecular NIR-II dye BDF1005 is designed and synthesized with strong NIR-I absorption at 768 nm and bright NIR-II peak emission at 1034 nm. In vitro and in vivo experiments demonstrate that BDF1005-based nanotheranostics can be applied for NIR-II fluorescence imaging-guided photothermal therapy of 4T1 tumor-bearing mice. Under 808 nm laser irradiation, tumor growth can be effectively inhibited. This work opens up a new road for the exploitation of NIR-II small molecular dyes for cancer phototheranostics.

Warhead power assessment of the anti-ship missile plays a vital role in determining the optimal design of missile, thus having important strategic research significance. However, in the assessment process, expert’s judgement will directly affect the assessment accuracy. In addition, there are many criteria involved in the missile design alternatives. Some criteria with poor performance may be compensated by other criteria with excellent performance, and then it is impossible to find the truly optimal alternative. Aimed at solving these problems, this paper proposes a synthetical assessment process based on fuzzy hesitant linguistic term set and the Gained and Lost Dominance Score (GLDS) method. In order to improve the assessment accuracy of experts and solve the problem that experts generate different opinions, combined with the advantages of fuzzy hesitant sets and linguistic term sets, the double hierarchy hesitant fuzzy linguistic term sets are used in this paper to improve the accuracy of expert’s judgement. In order to effectively combine expert’s experience with the data of criteria, the evidence theory and entropy weight method are used to transfer the expert’s judgement to the weight. In order to avoid selecting defective alternative of missile design, the GLDS is used to fuse expert information and criteria information. Sensitivity analysis shows that the assessment process has sensitivity to some extent. However, when the fluctuation of expert’s assessment makes the fluctuation of θ in the range of −5% to 5%, the impact on the results is not quite conspicuous. The analysis of calculation result and comparative analysis show that the assessment process proposed in this paper is accurate enough, has great advantage in selecting the current and potential optimal alternative of missile design, and avoids the alternatives with low criteria performance that cannot be compensated by other criteria being selected.

Cancer is one of the leading causes of human death around the world. Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is an emerging light-triggered cancer treatment and shows the advantages of non-invasiveness and low side effects. The design and preparation of efficient phototherapeutic agents are of great significance for phototherapy. Diketopyrrolopyrrole (DPP) is a small molecular organic dye featuring outstanding photophysical properties, facile tuning of structures and properties, and excellent photostability; thus, phototherapeutic agents based on organic small molecular DPP derivatives have attracted significant research attention for not only phototherapy but also photodiagnosis of fluorescence imaging (FLI) and photoacoustic imaging (PAI). This review summarizes the recent progress of various DPP-based organic small molecules on phototheranostics during the last five years. The molecular structure design and their phototheranostics performances are discussed in detail, as will be of great help for further creation of DPP-based phototheranostics.

Aiming at the thermal insulation problem of vehicle shelter in high heat and cold environment, with polyurethane foam as the base material, vacuum insulation board and aerogel with low thermal conductivity as the core material, a new composite insulation structure called dual-core cladding thermal insulation structure suitable for vehicle shelter is proposed. Based on the secondary development of ANSYS, the batch CFD simulation of the sample points of the dual-core cladding thermal insulation structure is realized, and it is concluded that its surface density increases linearly and effective thermal conductivity decreases nonlinearly with the increasing of thickness of the core material. Comparing with aerogel, the thickness of the vacuum insulation board has a more obvious influence on the performance of the insulation structure. The proxy model and the second-generation non-inferior ranking genetic algorithm are used to perform the multi-objective optimization of performance of the dual-core cladding thermal insulation structure. After optimization, the effective thermal conductivity of the thermal insulation structure reduced by 55.56%, and the thermal insulation effect is better than that of the single-core thermal insulation structure. The new dual-core cladding thermal insulation structure was applied to the middle roof of a vehicle shelter, the analysis results showed that the heat transfer coefficient of the middle roof reduced by 15.76% under the requirement of surface density, which improved significantly the heat insulation performance of the vehicle shelter slab.

The energy consumption and carbon dioxide emissions of tourism industry in China have become issues that cannot be ignored, putting pressure on the natural environment. This study uses Data Envelopment Analysis–Malmquist Index (MI) model to analyze the temporal and spatial evolution process of low-carbon tourism industry efficiency in Heilongjiang Province from 2010 to 2019. The results show that from 2010 to 2019, the technical efficiency (TE) of low-carbon tourism industry in 12 regions of Heilongjiang Province was significantly different and shows a growth trend. The pure technical efficiency (PTE) in Qiqihar, Jixi and Yichun had a more significant impact on the TE, and PTE had a greater impact on the development of low-carbon tourism economy in these regions. Hegang, Daqing, Shuangyashan, Kiamusze, Heihe and Suihua have a higher MI, and the TE has maintained a stable growth state overall.

Amorphous silica nanoparticles (ASiNPs) are generally considered to be biocompatible with limited acute toxicity. These nanoparticles were therefore exploited in diverse nanoproducts (e.g. foods and cosmetics) and may be released into environments in daily life. This has led to substantial concerns on their affects by long-term exposure. Herein, Raw264.7 cells were subjected to long-term exposure of ASiNPs for assessment of the potential cytotoxicity. Two ASiNPs with diameters of 50 ~ 100 nm (ASiNP1) and 450 ~ 500 nm (ASiNP2) were synthesized and comprehensively characterized. The acquired cells were denoted as Raw264.7-NP1 (ASiNP1 treatment) and Raw264.7-NP2 (ASiNP2 treatment) after long-term exposure. Both the small and large ASiNPs showed similar cellular distributions in lysosomes. We therefore examined the impacts of ASiNPs in lysosomal density, size and function by microscopy imaging and proteomics analysis. As a result, Raw264.7-NP1 cells displayed 2.3-fold higher lysosomal density and 149% increments of average lysosomal area than parent cells. Proteomics analysis of lysosomes revealed 25 significantly changed proteins closely relating to 5 cellular effects, including autophagy and lipid metabolism. Confocal imaging and immunoblotting of LC-3 proteins indicated an accumulation of autophagosomes in Raw264.7-NP1 cells. Elevation of cholesterol was also demonstrated in Raw264.7-NP1 cells by visualization and quantification of cellular cholesterols. Notably, the cholesterol elevation in Raw264.7-NP1 cells could be ameliorated by acceleration of autophagic flux (rapamycin treatment) but aggregated by blockage of autolysosome formation (chloroquine treatment), indicating the critical role of autophagic flux in lipid metabolism. Overall, the discovery of these hazard effects raised warnings for the long-term uses of ASiNP-based nanoproducts and may facilitate the decision making on environmental exposure thresholds of ASiNPs.

Narrowband cyan photoluminescence and long-lasting UVA persistent luminescence have been successfully achieved in Sr3Sc2Ge3O12:Bi3+ phosphors by selective site occupation.

Expeditious highly C6-regioselective acylation of purines and purine nucleosides via a traceless proton aided approach at room temperature without metal catalysts is reported for the first time.

K0.3Bi0.7F2.4-based nanoscintillators with multiform morphologies are synthesized through an ultrafast (only 1 min) and aqueous-phase chemical method at room temperature, which exhibit great potential for X-ray detection and imaging applications.

Synergic effect of graphene oxide (GO) and silicon nitride whisker (Si3N4w) on the mechanical properties of nacre-like alumina was investigated in this study. A comprehensive analysis on the composites, including microstructure, relative densities, flexural strength and fracture toughness, was carried out. The experimental results showed that, GO promoted the fracture toughness of the composites, but reduced the flexural strength slightly; while adding a certain amount of Si3N4w improved both flexural strength and fracture toughness. With the incorporation of GO and Si3N4w, the highest flexural strength reached 520 MPa and the fracture toughness reached 9.59 MPa m1/2. Microstructure observation revealed that the enhanced mechanical properties were ascribed to the synergistic toughening mechanisms induced by the nacre-like structure of alumina, GO pull-out, Si3N4w pinning and pull-out.

Virtualized network slicing allows a multitude of logical networks to be created on a common substrate infrastructure to support diverse services. A virtualized network slice is a logical combination of multiple virtual network functions, which run on virtual machines (VMs) as software applications by virtualization techniques. As the performance of network slices hinges on the normal running of VMs, detecting and analyzing anomalies in VMs are critical. Based on the three-tier management framework of virtualized network slicing, we first develop a federated learning (FL) based three-tier distributed VM anomaly detection framework, which enables distributed network slice managers to collaboratively train a global VM anomaly detection model while keeping metrics data locally. The high-dimensional, imbalanced, and distributed data features in virtualized network slicing scenarios invalidate the existing anomaly detection models. Considering the powerful ability of generative adversarial network (GAN) in capturing the distribution from complex data, we design a new multi-discriminator Bidirectional Wasserstein GAN with Gradient Penalty (BiWGAN-GP) model to learn the normal data distribution from high-dimensional resource metrics datasets that are spread on multiple VM monitors. The multi-discriminator BiWGAN-GP model can be trained over distributed data sources, which avoids high communication and computation overhead caused by the centralized collection and processing of local data. We define an anomaly score as the discriminant criterion to quantify the deviation of new metrics data from the learned normal distribution to detect abnormal behaviors arising in VMs. The efficiency and effectiveness of the proposed collaborative anomaly detection algorithm are validated through extensive experimental evaluation on a real-world dataset., Accepted for publication in IEEE Transactions on Mobile Computing

In response to carbon peak and carbon neutrality targets, a broad industrial transformation is underway in China's tourism industry. This paper applies the Data Envelopment Analysis (DEA) model to calculate the efficiency of the tourism industry under carbon emission constraints and further investigates its influencing factors through the Tobit regression. The results are as follows: (1) The tourism efficiency under carbon emission constraints of China from 2000 to 2019 showed a trend of first rising and then declining, and there were obvious regional differences; (2) The total factor productivity of tourism in China increased significantly from 2000 to 2019, the contribution of technical progress, pure technical efficiency, and scale efficiency to it decrease in succession; (3) The factors of industrial structure, transportation convenience, economic development level, degree of opening to the outside world, the level of scientific and technological development have varying degrees of influence on tourism efficiency. Based on the analysis results, this paper puts forward several policy recommendations on tourism efficiency and low-carbon development. The conclusions of this paper are of certain significance for developing countries to improve tourism efficiency and achieve high-quality development of tourism industry in the context of sustainable development.

This study was to investigate the value of ultrasound technology based on the bilateral filtering noise elimination algorithm in evaluating the neuroprotective effect of monosialoganglioside in ketamine-anesthetized Parkinson’s disease patients. The research subjects were 75 patients with Parkinson’s disease admitted to the hospital. The patients were randomly divided into three groups according to different treatment methods: A (GM1 + ketamine anesthesia group), B (conventional treatment + ketamine anesthesia group), and C (GM1 + nonketamine anesthesia group), with 25 patients in each group. Twenty-five healthy people with similar general data in the three groups (groups A, B, and C) were also selected as the control group (group D). All patients underwent ultrasonography, and ultrasound images were processed using the bilateral filter noise elimination. Structural similarity (SSIM), mean absolute error (MAE), and peak signal to noise ratio (PSNR) were used to evaluate the treatment effect. Plasma phospholipids, the third part of the PD unified score scale, Montreal cognitive assessment scale, and other indicators were analyzed and compared among the four groups. The bilateral filtering image noise was effectively suppressed, and the edge details were kept well. Some of the weak edges and texture information in the image were eliminated, the visual effect was ideal, and the accuracy of the edges of the picture remained good. The serotonin lipid level in group A was greatly lower than the serum phospholipid level in group B after GM1 treatment (6.55 VS 7.84, P < 0.05 ). Compared with that before treatment, the serotonin lipid level of group A patients decreased after the treatment, and the difference was considerable (7.46 VS 6.55, P < 0.05 ). In short, GM1 had a protective effect on the nerves of patients with Parkinson’s disease anesthetized by ketamine.

A: Characteristics of spermatozoa in asthenoteratozoospermia affected man. B: Pedigree and Sanger sequencing analysis of the family. C: The effect of the missense variant in the CCIN gene. This article is protected by copyright. All rights reserved.

Persistent phosphors emitting in the narrowband ultraviolet-B (NB-UVB) spectral region have aroused significant interest, owing to their special self-illuminating feature in realizing many advanced technological applications under excitation-free conditions, such as dermatological therapy and invisible optical tagging. Here, we focus our discussion on a new Gd

Characterized by large plastic deformation and energy-dissipation capacity, low-yield-strength steel shear panel dampers (LYSPDs) are widely used as energy-dissipating members in seismic engineering. However, the effect of welding on the properties of LYSPDs remains unclear. Hence, in this study, we investigated the matching performance between low-yield-strength steel (LYS) and two different welding materials. Subsequently, the quality of welding between LYS and dissimilar metals was investigated. Furthermore, the fracture characteristics of the welding seam of LYS under large plastic deformation were explored. Finally, the welding performance of LYSPDs under large plastic deformation was verified under cyclic loading. The results of this study are significant in terms of the effect of welding on the properties of LYSPDs.

The variation characteristics of growth stages of winter wheat (Triticum aestivum L.) with the climate change were measured by designing its stability and prediction model. Results showed the trend of stability of growth stage of winter wheat in Jiangsu province of China was an S-shaped curve indicating the growth of winter wheat was more stable in late stage. The lengths of early and late stages of growth were in inverse proportion. Specifically, when the early stage was prolonged, the late stage was shortened, which ensured the relative stability of the length of growth stage. The length of growth stage was correlated with the meteorological conditions. Thus, favorable meteorological conditions contributed to the stability of growth stages of winter wheat. Along with the climate change, the basic statistical characteristics of growth stage remained stable. Each stage drifted moderately under the variation of meteorological conditions, typically during the stage of vegetative growth. The growth process can be regulated by means of variety improvement, adjustment of sowing time and density, reasonable fertilization, and the use of growth regulators. These measures are able to counteract the influences of climate change on winter wheat production and ensure the production security. Bangladesh J. Bot. 50(3): 737-746, 2021 (September) Special

A clean air environment in the operating area is an important factor in reducing intraoperative infection, which is affected by medical staff and their dynamic behaviour. In this study, experimental and numerical simulation methods were used to investigate the cleaning performance of the operation area under actual working conditions, which can more intuitively simulate the movement of particles in the operating room. First, four air distribution cases are studied: empty state, static persons, arm waving, and medical staff walking. Second, the disturbance process, distribution, peak value, and uniformity of particulate matter concentration in these cases are discussed. The results show that the air distribution in the operation area is greatly affected by the dynamic disturbance, the cleanliness level deteriorates by 2–3 levels, and the cleanliness uniformity also deteriorates further. Therefore, it is important to reasonably evaluate the mobile operation shelter cleaning performance and infection risk under actual working conditions.