The investigation of multiple factors on elastic anisotropy of artificial shale based on the orthogonal experiment

Elastic anisotropy of shales is critical to accurate constraints for rock physical models,quantitative interpretation and hydraulic fracturing.However,the causes of elastic anisotropy of shales are very complicated,and the understanding of how multiple influence factors affect the elastic anisotropy of shales is still not clear.Hence,the orthogonal experiment,as an effective multiple factors experimental method,is adopted in this study to analyze the effect of multiple factors for shale elastic anisotropy.Three factors,clay content,organic matter(OM)content and compaction stress are selected as independent variables,the orthogonal test table L_(16)(4^(3))with four levels for each factor is adopted.According to the designed orthogonal table,sixteen artificial shales are constructed based on the cold-pressing method,and all the dry artificial shales are measured by the ultrasonic measurements.The influence of each factor on the elastic anisotropy and the sensitivity orders of three factors are obtained using the range analysis.The orders of sensitivity for selected factors follow the sequence clay content>compaction stress>OM content for velocity anisotropy parameters.The compaction mechanism of artificial shales is also discussed by the compaction factor,which are positively correlated with the velocity anisotropy parameters.The clay platelets orientation distribution function(ODF)of samples is evaluated by a theoretical model,the ODF coefficients are significantly affected by the clay content and compaction stress,and W200 are much more sensitive to these factors than W400.The results can provide a critical rock physics basis for quantitative interpretation and reservoir prediction of the low-maturity or maturity shale reservoir.

Convective clouds detection in satellite cloud image using fast fuzzy support vector machine

Support vector machine(SVM)is easily affected by noises and outliers,and its training time dramatically increases with the growing in number of training samples.Satellite cloud image may easily be deteriorated by noises and intensity non-uniformity with a huge amount of data needs to be processed regularly,so it is hard to detect convective clouds in satellite image using traditional SVM.To deal with this problem,a novel method for detection of convective clouds was proposed based on fast fuzzy support vector machine(FFSVM).FFSVM was constructed by eliminating feeble samples and designing new membership function as two aspects.Firstly,according to the distribution characteristics of fuzzy inseparable sample set and the fact that the classification hyper-plane is only determined by support vectors,this paper uses SVDD,Gaussian model and border vector extraction model comprehensively to design a sample selection method in three steps,which can eliminate most of redundant samples and keep possible support vectors.Then,by defining adaptive parameters related to attenuation rate and critical membership on the basis of the distribution characteristics of training set,an adaptive membership function is designed.Finally,the FFSVM is trained by the remaining samples using adaptive membership function to detect convective clouds.The experiments on FY-2D satellite images show that the proposed method,compared with traditional FSVM,not only remarkably reduces training time,but also further improves the accuracy of convective clouds detection.

A physical model study of shale seismic responses and anisotropic inversion

The seismic responses of the shale properties are critical for shale gas reservoir evaluation and production.It has been widely reported that the clay minerals have substantial influences on the seismic wave anisotropy and brittleness.Hence,knowing the seismic responses of the clay-rich shales and estimation of shale elastic properties are significant for the shale gas industry.A physical model containing two groups of shale blocks as the target formations is constructed in laboratory.The group S contains six shale blocks with different clay contents,and the group N contains six shale blocks with different porosity.The acquired 2D seismic data is used to analyze the seismic responses of two corresponding seismic lines.An anisotropic three-term inversion method is applied to one of the seismic inline to estimate the elastic properties the target shale blocks.The inversed attributes can be used to reveal the effects of shale clay contents.This study shows the substantial significance of using a physical model to observe the seismic responses of shale properties.The inversion results indicate that the anisotropic three-term inversion method could provide accurate results of elastic properties as well as the P-wave anisotropy parameter for shale formations.

H_(2)O_(2)-sensitive nanoscale coordination polymers for photoacoustic tumors imaging via in vivo chromogenic assay

Photoacoustic(PA)imaging with much deeper tissue penetration and better spatial resolution had been widely employed for the prevention and diagnosis of many diseases.In this study,a new type of hydrogen peroxide(H_(2)O_(2)T-activated photoacoustic nanoprobe[Mn-AH nanoscale coordination polymer nanodots(NCPs)]was successfully synthesized by a simple one-step method in water phase containing 2,20-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS),horse radish peroxidase(HRP),and manganese ion(Mn^(2+).After modification by polyethylene glycol(PEG),Mn-AH NCPs exhibited excellent stability and biocompatibility for in vivo H_(2)O_(2)-responsive chromogenic assay with great speci¯city and sensitivity.In the presence of H_(2)O_(2),colorless ABTS would be converted by HRP into the oxidized form with strong near-infrared(NIR)absorbance,enabling photoacoustic detection of endogenous H_(2)O_(2).Using H_(2)O_(2)-activated Mn-AH NCPs,we have successfully performed PA imaging and H_(2)O_(2)detection of subcutaneous murine colon CT26 tumor and deep-seated orthotopic bladder tumor.Due to the inherent Mn element existence inside the Mn-AH,this nanoprobe also serves as a good T1-weighted magnetic resonance imaging(MRI)contrast agent simultaneously.Lastly,after accomplishing its imaging functions,the Mn-AH NCPs could be cleared out from the body without any long-term toxicity,providing a new opportunity for cancer diagnosis and treatment.

利用超构表面减少介子波导的串扰

宽波段低损耗的单模传输方式使得介质型波导（dielectric waveguides,DWs）在上个世纪得到了广泛研究。传统的介质波导通常由低介电常数的轻量化材料组成,能量约束差,导致相邻波导间具有严重的串扰影响,阻碍了系统的集成化和微型化。

MKK7-mediated phosphorylation of JNKs regulates the proliferation and apoptosis of human spermatogonial stem cells

BACKGROUND Human spermatogonial stem cells(SSCs)are the basis of spermatogenesis.However,little is known about the developmental regulatory mechanisms of SSC due to sample origin and species differences.AIM To investigates the mechanisms involved in the proliferation of human SSC.METHODS The expression of mitogen-activated protein kinase kinase 7(MKK7)in human testis was identified using immunohistochemistry and western blotting(WB).MKK7 was knocked down using small interfering RNA,and cell proliferation and apoptosis were detected by WB,EdU,cell counting kit-8 and fluorescenceactivated cell sorting.After bioinformatic analysis,the interaction of MKK7 with c-Jun N-terminal kinases(JNKs)was verified by protein co-immunoprecipitation and WB.The phosphorylation of JNKs was inhibited by SP600125,and the phenotypic changes were detected by WB,cell counting kit-8 and fluorescenceactivated cell sorting.RESULTS MKK7 is mainly expressed in human SSCs,and MKK7 knockdown inhibits SSC proliferation and promotes their apoptosis.MKK7 mediated the phosphorylation of JNKs,and after inhibiting the phosphorylation of JNKs,the phenotypic changes of the cells were similar to those after MKK7 downregulation.The expression of MKK7 was significantly downregulated in patients with abnormal spermatogenesis,suggesting that abnormal MKK7 may be associated with spermatogenesis impairment.CONCLUSION MKK7 regulates the proliferation and apoptosis of human SSC by mediating the phosphorylation of JNKs.

COVID-19 and gastroenteric manifestations

Coronavirus disease 2019(COVID-19),caused by the infection of a novel coronavirus[severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)],has become a pandemic.The infection has resulted in about one hundred million COVID-19 cases and millions of deaths.Although SARS-CoV-2 mainly spreads through the air and impairs the function of the respiratory system,it also attacks the gastrointestinal epithelial cells through the same receptor,angiotensin converting enzyme 2 receptor,which results in gastroenteric symptoms and potential fecal-oral transmission.Besides the infection of SARS-CoV-2,the treatments of COVID-19 also contribute to the gastroenteric manifestations due to the adverse drug reactions of anti-COVID-19 drugs.In this review,we update the clinical features,basic studies,and clinical practices of COVID-19-associated gastroenteric manifestations.

Defects in phospholipase C zeta cause polyspermy and low fertilization after conventional IVF:not just ICSI failure

Phospholipase C zeta(PLC)is a key sperm-borne oocyte-activating factor that triggers Ca^(2+)oscillations and the subsequent block to polyspermy following gamete fusion.Mutations in PLCZ1,the gene encoding PLCζ,cause male infertility and intracytoplasmic sperm injection(ICSI)fertilization failure;and PLCζ expression and localization patterns are significantly correlated with ICSI fertilization rate(FR).However,in conventional in vitro fertilization(cIVF),whether and how sperm PLCζ affects fertilization remain unclear.Herein,we identified one previously reported and two novel PLCZ1 mutations associated with polyspermy in vitro that are characterized by excessive sperm-zona binding and a delay in pronuclei(PN)formation.Immunofluorescence staining and oocyte activation testing revealed that virtually all spermatozoa from patients lacked functional PLCζ and were thus unable to evoke Ca^(2+) oscillations.ICSI with an artificial oocyte activation treatment successfully rescued the polyspermic phenotype and resulted in a live birth.Furthermore,we analyzed PLCζ in an additional 58 males after cIVF treatment in the Reproductive and Genetic Hospital of CiTiC-Xiangya(Changsha,China)between February 2019 and January 2022.We found that the proportion of spermatozoa that expressed PLCζ was positively correlated with both 2PN rate and total FR.The optimal cutoff value below which males were likely to experience low FR(total FR≤30%)after clVF was 56.7%for the proportion of spermatozoa expressing PLC5.Our study expands the mutation and the phenotypic spectrum of PLCZ1 and further suggests that PLCζ constitutes a promising biomarker for identifying low FRs cases in cIVF due to sperm-related oocyte activation deficiency and that sperm PLCζ analysis may benefit the widermale population and not onlymen with IcsI failure.

具有涡流热效应的液态金属微球用于磁热增强的癌症栓塞-免疫联合治疗

肝细胞癌患者由于肝癌的高转移性和高复发率表现出预后差的特征.本文提出了一种通过磁热疗法(MHT)增强癌症免疫治疗联合经导管动脉栓塞(TAE)治疗肝癌肿瘤的有效策略.通过微流控技术制备的尺寸均匀液态金属微球(LM MSs),由于在交变磁场下的涡流热效应表现出显著的磁感应加热能力,可同时作为MHT和TAE两种癌症治疗策略的有效药物.一方面,LM MSs优异的涡流磁热效应表现出高效的MHT治疗疗效.另一方面,LM MSs引发的MHT可以显著增强免疫系统激活,促进免疫细胞的浸润;与免疫检查点阻断(ICB)治疗联合后可以进一步刺激强大的免疫应答,从而抑制远端肿瘤的生长.此外,LM MSs-碘油栓塞剂在兔子原位肝癌模型中表现出优异的栓塞-磁热联合治疗效果.总之,该工作不仅证明了LM MSs可以作为有效的MHT试剂实现MHT-免疫联合治疗,而且还展示了TAE与MHT联合治疗在原位大型肝肿瘤治疗中的重要应用前景.

Novel multiple object tracking method for yellow feather broilers in a flat breeding chamber based on improved YOLOv3 and deep SORT

Aiming at the difficulties of the health status recognition of yellow feather broilers in large-scale broiler farms and the low recognition rate of current models,a novel method based on machine vision to achieve precise tracking of multiple broilers was proposed in this paper.Broilers’behavior in the breeding environment can be tracked to analyze their behaviors and health status further.An improved YOLOv3(You Only Look Once v3)algorithm was used as the detector of the Deep SORT(Simple Online and Realtime Tracking)algorithm to realize the multiple object tracking of yellow feather broilers in the flat breeding chamber,which replaced the backbone of YOLOv3 with MobileNetV2 to improve the inference speed of the detection module.The DRSN(Deep Residual Shrinkage Network)was integrated with MobileNetV2 to enhance the feature extraction capability of the network.Moreover,in view of the slight change in the individual size of the yellow feather broiler,the feature fusion network was also redesigned by combining it with the attention mechanism to enable the adaptive learning of the objects’multi-scale features.Compared with traditional YOLOv3,improved YOLOv3 achieves 93.2%mAP(mean Average Precision)and 29 fps(frames per second),representing high-precision real-time detection performance.Furthermore,while the MOTA(Multiple Object Tracking Accuracy)increases from 51%to 54%,the IDSW(Identity Switch)decreases by 62.2%compared with traditional YOLOv3-based objective detectors.The proposed algorithm can provide a technical reference for analyzing the behavioral perception and health status of broilers in the flat breeding environment.

Use of electroacupuncture and transcutaneous electrical acupoint stimulation in reproductive medicine:a group consensus

Abstract： With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture （EA） and transcutaneous electrical acupoint stimulation （TEAS）, become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of ENTEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/rEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome （PCOS）, pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligosperrnia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.

Influence of sperm morphology on pregnancy outcome and offspring in in vitro fertilization and intracytoplasmic sperm injection:a matched case-control study

Sperm morphology was once believed as one of the most predictive indicators of pregnancy outcome in assisted reproductive technology(ART).However,the impact of teratozoospermia on in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI)outcomes and its offspring remains inconclusive.In order to evaluate the influence of teratozoospermia on pregnancy outcome and newborn status after IVF and ICSI,a retrospective study was conducted.This was a matched case-control study that included 2202 IVF cycles and 2574 ICSI cycles and was conducted at the Reproductive and Genetic Hospital of CITIC-Xiangya in Changsha,China,from June 2013 to June 2018.Patients were divided into two groups based on sperm morphology:teratozoospermia and normal sperm group.The pregnancy outcome and newborn outcome were analyzed.The results indicated that couples with teratozoospermia had a significantly lower optimal embryo rate compared to those with normal sperm morphology in IVF(P=0.007),while there were no statistically significant differences between the two groups in terms of the fertilization rate,cleavage rate,implantation rate,and pregnancy rate(all P>0.05).Additionally,teratozoospermia was associated with lower infant birth weight in multiple births after IVF.With regard to ICSI,there was no significant difference in both pregnancy outcome and newborn outcome between the teratozoospermia and normal groups(both P>0.05).Furthermore,no increase in the risk of birth defects occurred in the teratozoospermia group after IVF/ICSI.Consequently,we believe that teratozoospermia has limited predictive value for pregnancy outcomes in IVF/ICSI,and has little impact on the resulting offspring if multiple pregnancy is avoided.

Natural product curcumin-based coordination nanoparticles for treating osteoarthritis via targeting Nrf2 and blocking NLRP3 inflammasome

Oxidative stress leads to chondrocyte apoptosis and extracellular matrix(ECM)degradation,thus contributing to the pathogenesis of osteoarthritis(OA).Herein,curcumin with remarkable antioxidant and anti-inflammatory activities has been employed as an organic ligand to coordinate ferric ions for enhancing the water-solubility and biocompatibility of natural product curcumin.The obtained iron-curcumin-based coordination nanoparticles(Fe-Cur NPs)exhibit great water-solubility and efficient reactive oxygen/nitrogen species(ROS/RNS)scavenging ability.In vitro chondrocyte evaluation experiments indicated that the intracellular ROS/RNS induced by interleukin 1β(IL-1β)could be efficiently scavenged by these Fe-Cur NPs and oxidative-stressinduced cell death could be preserved as well.In addition,post intra-articular(i.a.)injection into OA rat joints,Fe-Cur NPs could greatly inhibit OA progression via activating the nuclear factor-erythroid 2 related factor-2(Nrf2)and inhibiting nod-like receptor protein-3(NLRP3)inflammasome activation in primary rat chondrocytes,as well as decrease the production of matrix degrading proteases and other inflammatory mediators.The efficient antioxidation and anti-inflammation performance of Fe-Cur NPs endow them as a promising nanoplatform for treatment of various inflammatory diseases,and more detailed researches will be conducted in the future.

Titanium carbide nanosheets with defect structure for photothermal-enhanced sonodynamic therapy

Sonodynamic therapy(SDT)has attracted widespread interest in biomedicine,owing to its novel and noninvasive therapeutic method triggered by ultrasound(US).Herein,the Ti_(3)C_(2) MXene nanosheets(Ti_(3)C_(2) NSs)are developed as good sonosensitizers via a two-step method of chemical exfoliation and high-temperature treatment.With the high-temperature treatment,the oxygen defect of Ti_(3)C_(2) MXene nanosheets(H-Ti_(3)C_(2) NSs)is greatly increased.Therefore,the electron(e^(-))and hole(h^(+))generated by US can be separated faster due to the improved degree of oxidation,and then the recombination of e^(-)-h^(+)can be prevented with the abundant oxygen defect under US irradiation,which induced the sonodynamic efficiency greatly to improve around 3.7-fold compared with Ti_(3)C_(2) NSs without high-temperature treatment.After PEGylation,the H-Ti_(3)C_(2)-PEG NSs show good stability and biocompatibility.In vitro studies exhibit that the inherent property of mild photothermal effect can promote the endocytosis of H-Ti_(3)C_(2)-PEG NSs,which can improve the SDT efficacy.In vivo studies further display that the increased blood supply by the mild photothermal effect can significantly relieve hypoxia in the tumor microenvironment,showing photothermal therapy(PTT)enhanced SDT.Most importantly,the H-Ti_(3)C_(2)-PEG NSs can be biodegraded and excreted out of the body,showing no significant long-term toxicity.Our work develops the defective H-Ti_(3)C_(2) NSs as high-efficiency and safe sonosensitizers for photothermal-enhanced SDT of cancer,extending the biomedical application of MXene-based nanoplatforms.

Phthalocyanine iron nanodots for combined chemodynamic-sonodynamic cancer therapy

Sonodynamic therapy(SDT)is a new non-invasive treatment method that has received widespread attention due to its deep tissue penetration and high safety.However,the low sonodynamic efficiency of sonosensitizers makes SDT poorly effective and limits its bioapplication.Therefore,it is urgent to prepare safe and highly efficient sonosensitizers.Herein,a new kind of sonosensitizer,iron phthalocyanine nanodots(FePc NDs),is fabricated via a facile thermal organic-phase synthesis procedure for enhanced SDT against cancer.Due to the presence of Fe,FePc NDs can also be used as Fenton reagents to efficiently generate hydroxyl radicals(·OH)in the presence of hydrogen peroxide(H_(2)O_(2)).Notably,after modification with polyethylene glycol(PEG),FePc-PEG NDs exhibit remarkable biocompatibility and physiological stability,as well as good tumor accumulation ability.Compared with the control group,in vitro and in vivo experimental results demonstrate obvious cell killing efficiency and significant tumor suppression with the treatment of FePc-PEG NDs under ultrasound(US)irradiation.More importantly,FePc-PEG NDs have good biological safety and do not cause any adverse effects on mice.Our work highlights the use of FePc-PEG NDs as a highly effective and low-toxic sonosensitizer for enhanced SDT.

A recurrent mutation in TBPL2 causes diminished ovarian reserve and female infertility

Diminished ovarian reserve(DOR)is a disorder of ovarian function in which the ovary loses its normal reproductive potential,including decreasing oocyte quantity and quality.The disorder is associated with infertility in women of reproductive age with regular menses and poor response to controlled ovarian hyperstimulation(Broekmans et al.,2009).

Comparison of Hormonal and Metabolic Characteristics and Ovary Response to Induced Ovulation in Amenorrheic and Oligomenorrheic Women with PCOS

Objective To compare differences in endocrine and metabolic characteristics and response to induced ovulation treatment between oligomenorrheic and amenorrheic women with polycystic ovary syndrome （PCOS）.Methods A total of 154 infertile PCOS patients presenting with oligomenorrhea or amenorrhea were retrospectively analysed, the differences in endocrine and metabolic characteristics and induced ovulation outcome parameters between oligomenorrheic and amenorrheic women were compared.Results Total follicle count, serum levels of total testosterone （TT）, luteotropic hormone （LH） and insulin resistant index （HOMA-IR） were significantly higher in amenorrheic patients compared with oligomenorrheic patients （P 〈O. 05）. There were no differences in age, body mass index （BMI）, follicle stimulating hormone （FSH）, glucose, insulin levels and lipid level between the two groups. During clomiphene citrate （CC） and hMG induced ovulation （203 cycles）, the ovulation rate in amenorrheic group was significantly lower than that of oligomenorrheic group （84.62% vs 96.80%, P 〈0.01）. The duration to reach a dominant follicle, the cycles need to add hMG and the total dose of hMG were higher in women with amenorrhea compared with those with oligomenorrhea. No significant differences were found between the two groups in the total number of mature follicles, estradiol level and endometrial thickness on the day of hCG administration and pregnancy rate. Conclusion The degree of cycle irregularity might be a simple and effective clinical parameter to estimate the degree of metabolic and endocrine disorders and response to induced ovulation.

A Modified Ultra-Long Downregulation Protocol Improves Pregnancy Outcomes in High Body Mass Index Patients Undergoing In vitro Fertilization/Intracytoplasmic Sperm Injection Treatment

Objective:Overweight and obesity are increasingly epidemic and negatively related to reproductive outcome.The aim of this study was to investigate the advantages of a modified ultra-long downregulation protocol on pregnancy outcomes of patients with high body mass index(BMI)undergoingin vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI),compared to the long protocol(LP).Methods:We retrospectively analyzed the clinical data of 3,920 infertile patients at the Reproductive and Genetic Hospital of Citic-Xiangya from January 2012 to December 2017 by propensity score matching(PSM).Patients were divided into two groups:modified ultra-LP(MULP)(n=1,960)and LP(n=1,960).Results:In the MULP group,live birth rate(52.65%vs.46.79%,P<0.001,odds ratio[OR]:1.784,95%confidence interval[CI]:1.563-2.036),clinical pregnancy rate(62.50%vs.57.91%,P=0.003,OR:1.211,95%CI:1.066-1.377),and implantation rate(53.24%vs.49.65%,P=0.004,OR:1.155,95%CI:1.048-1.272)were statistically significantly higher than those of the LP group.Moreover,the cycle cancellation rates(12.70%vs.15.15%,P=0.027,OR:0.815,95%CI:0.68-0.977),abortion rates(12%vs.14.8%,P=0.046,OR:0.785,95%CI:0.619-0.996),and ectopic pregnancy rates(1.06%vs.2.11%,P=0.04,OR:0.497,95%CI:0.252-0.98)were lower than those in the LP group.Conclusion:The modified ultra-long downregulation protocol improved the pregnancy outcomes in patients with high BMI undergoing IVF/ICSI treatment,providing a potential option for physicians when deciding an optimized ovary stimulation protocol for high BMI patients.