Insights into in-situ imbibition behavior of fracturing fluid in propped shale fractures based on nuclear magnetic resonance:A case study from Longmaxi Formation shale,Sichuan Basin,China

Shale gas is an important component of unconventional oil and gas resources.Studying the imbibition behavior is helpful to optimize flowback parameters and enhance gas recovery.Recent imbibition studies have focused on shale matrix,and the pressure conditions discussed were mostly atmospheric.The initial imbibition behavior begins from propped fractures to matrix,but there are few studies working on explaining the imbibition behavior in propped fractures or the phenomenon of many shale wells exhibit higher productivity after a“soaking”period.Therefore,propped fracture samples were designed for imbibition and migration experiments.In order to accurately study the mechanism and main influencing factors of fracturing fluid imbibition and migration in propped and unpropped shale fractures under high temperature and high pressure,a series of experiments based on nuclear magnetic resonance(NMR)were carried out.Results showed that NMR T_(2) spectra of all samples exhibited a bimodal distribution.The final imbibition volume of fracturing fluid was positively related to pressure and fracture width.The imbibition effect of fracturing fluid was more evident in matrix pores under high pressure.In the migration during soaking stage,the fracturing fluid gradually migrated from large pores to small pores and gradually displaced the shale gas from the matrix,thus allowing the water blocking in propped fractures to self-unlock to some extent.Gas permeability decreased in the imbibition stage,while it recovered in the migration stage to some extent.

汉族人群Toll样受体3基因启动子区rs128912单核苷酸多态性与白内障的关系

目的:分析汉族人群Toll样受体3(TLR3)基因启动子区rs128912单核苷酸多态性(SNP)与白内障的关系。方法:选取2019-06/2021-06我院收治的白内障患者263例作为研究组,晶状体脱位患者150例作为对照组。采用免疫印迹法(Western blotting)检测两组患者晶状体前囊膜组织中TLR3蛋白表达情况,采用直接测序法分析TLR3基因启动子区rs128912位点多态性,采用实时荧光定量-聚合酶链式反应(RT-qPCR)法检测不同基因型患者外周血TLR3 mRNA表达情况。结果:研究组患者前囊膜组织中TLR3蛋白相对表达水平高于对照组(P<0.05)。研究组和对照组患者TLR3基因启动子区rs128912位点基因型(AA、AT、TT)频率均符合Hardy-Weinberg遗传平衡定律,且两组患者间TLR3基因启动子区rs128912位点基因型(AA、AT、TT)频率和等位基因(A、T)频率均有差异(P<0.05)。研究组中TT基因型患者外周血TLR3 mRNA相对表达水平均高于AA和AT基因型患者(P<0.05)。结论:白内障患者晶状体前囊膜组织中TLR3蛋白表达明显上调,且TLR3基因启动子区rs128912位点多态性与汉族人群白内障易感性有关,携带TT基因型者更易发生白内障。

Interstitial pneumonia combined with nocardia cyriacigeorgica infection:A case report

BACKGROUND Nocardia infection is a relatively uncommon disease,with no reports among patients with interstitial pneumonia.Due to its atypical clinical symptoms and chest computed tomography(CT)findings and the frequent yielding of negative results by conventional cultures,it poses challenges for timely diagnosis and treatment.CASE SUMMARY A 63-year-old female patient presented to our hospital in July 2022 with a 3-mo history of intermittent cough and poor appetite,accompanied by a 2-wk long duration of headaches.She had a previous medical history of interstitial pneumonia and was on oral prednisone and cyclosporine.Chest CT revealed the presence of newly developed round nodules.The diagnosis of Nocardia cyriacigeorgica infection was confirmed through metagenomic next-generation sequencing(mNGS)performed on bronchoalveolar lavage fluid.Targeted antiinfection therapy was initiated,resulting in symptom improvement and radiological resolution,further validating the mNGS results.CONCLUSION Nocardia cyriacigeorgica infection is a clinically rare condition that is primarily observed in immunocompromised patients.Its clinical and radiological manifestations lack specificity,but mNGS can aid in rapidly obtaining pathogenic information.Early initiation of targeted antimicrobial therapy based on mNGS results can improve patient prognosis.

Neural differentiation of human Wharton＇s jelly-derived mesenchymal stem cells improves the recovery of neurological function after transplantation in ischemic stroke rats

Human Wharton＇s jelly-derived mesenchymal stem cells（h WJ-MSCs）have excellent proliferative ability,differentiation ability,low immunogenicity,and can be easily obtained.However,there are few studies on their application in the treatment of ischemic stroke,therefore their therapeutic effect requires further verification.In this study,h WJ-MSCs were transplanted into an ischemic stroke rat model via the tail vein 48 hours after transient middle cerebral artery occlusion.After 4 weeks,neurological functions of the rats implanted with h WJ-MSCs were significantly recovered.Furthermore,many h WJ-MSCs homed to the ischemic frontal cortex whereby they differentiated into neuron-like cells at this region.These results confirm that h WJ-MSCs transplanted into the ischemic stroke rat can differentiate into neuron-like cells to improve rat neurological function and behavior.

Data reduction and calibration of the FMG onboard ASO-S

The Full-disk vector Magneto Graph(FMG)instrument will carry out polarization observations at one wavelength position of the Fe I 5324.179?spectral line.This paper describes how to choose this single wavelength position,the relevant data-processing and the magnetic field calibrations based on the measured polarization signals at one single wavelength position.It is found that solar radial Doppler velocity,which can cause the spectral line to shift,is a disadvantageous factor for the linear calibration at one wavelength position.Observations at two symmetric wavelength positions may significantly reduce the wavelength shift effect(~75%),but simulations show that such polarization signals located at the solar limbs(e.g.,beyond the longitude range of±30°)are not free from the effect completely.In future work,we plan to apply machine learning techniques to calibrate vector magnetic fields,or employ full Stokes parameter profile inversion techniques to obtain accurate vector magnetic fields,in order to complement the linear calibration at the single wavelength position.

Effects of luteinizing hormone and androgen on the development of rat progenitor Leydig cells in vitro and in vivo

Progenitor Leydig cells are derived from stem cells. The proliferation and differentiation of progenitor Leydig cells significantly contributes to Leydig cell number during puberty. However, the regulation of these processes remains unclear. The objective of the present study was to determine whether luteinizing hormone （LH） or androgen contributes to the proliferation and differentiation of progenitor Leydig cells. Fourteen-day-old male Sprague-Dawley rats were treated for 7 days with NalGlu, which is a gonadotropin- releasing hormone antagonist, to reduce the secretion of LH in the pituitary and thus, androgen in the testis. Rats were co-administered with LH or 7a-methyl-nortestosterone （MENT）, which is an androgen resistant to metabolism by 5a-reductase 1 in progenitor Leydig cells, and the subsequent effects of LH or androgen were measured. 3H-Thymidine was also intravenously injected into rats to study thymidine incorporation in progenitor Leydig cells. Progenitor Leydig cells were examined. NalGlu administration reduced progenitor Leydig cell proliferation by 83%. In addition, LH or MENT treatment restored Leydig cell proliferative capacity to 73% or 50% of control, respectively. The messenger RNA levels of proliferation-related genes were measured using real-time PCR. The expression levels of Igfl, Lifr, Pdgfra, Bcl2, Ccnd3and Pcnawere upregulated by MENT, and those of Pdgfra, Ccnd3and Pcnawere upregulated by LH. Both LH and MENT stimulated the differentiation of progenitor Leydig cells in vitro. We concluded that both LH and MENT were involved in regulating the development of progenitor Leydig cells.

Contrast in vulnerability to freezing-induced xylem embolism contributes to divergence in spring phenology between diffuse-and ring-porous temperate trees

Background:The spring phenology and growth strategy of temperate tree species can be strongly linked to their sensitivity to frosts,which deserve more profound investigations under the background of climate warming particularly considering the advancement of spring phenology as well as the increase in frequency and intensity of spring cold waves.Methods:Spring phenologies,stem radial growth characteristics,frost sensitivity of leaves and stem hydraulic systems were studied in five diffuse-porous and five ring-porous temperate tree species under a common garden condition.Results:The results showed that the spring leaf phenology of the diffuse-porous species was one to two weeks earlier than that of the ring-porous species.The ring-porous species had significantly higher stem hydraulic conductivity than the diffuse-porous species(1.81 and 0.95 kg·m^(-1)·s^(-1)·MPa^(-1),P<0.05)but were more vulnerable to freeze-thaw induced xylem embolism than the latter.After a simulated freeze-thaw event,the average percentage loss of hydraulic conductivity in the current year shoots increased from 26.0%(native embolism)to 86.7%in the ring-porous species,while it only increased from 21.3%to 38.3%in the diffuse-porous species.The spring phenology was clearly correlated with vulnerability to freeze-thaw induced embolism,with the more vulnerable ring-porous species exhibited substantially delayed phenology to reduce risks of catastrophic hydraulic dysfunction during spring frosts.Nevertheless,ring-porous species can offset the postponed onset of growth and gained even higher annual growth due to significantly higher hydraulic efficiency and leaf gas exchange rates.Conclusions:Contrasts between ring-porous and diffuse-porous species in resistance to freeze-thaw induced embolism suggest that they face different selective pressures from early spring frosts,which may at least be partially responsible for their divergence in spring phenology and growth strategy and can potentially lead to different responses to climate regime shifts.

Automatic detection and correction algorithms for magnetic saturation in the SMFT/HSOS longitudinal magnetograms

A longitudinal magnetic field often suffers the saturation effect in a strong magnetic field region when the measurement is performed at a single-wavelength point and linear calibration is adopted.In this study,we develop a method that can judge the threshold of saturation in Stokes V/I observed by the Solar Magnetic Field Telescope(SMFT)and correct it automatically.The procedure is to first perform the second-order polynomial fit to the Stokes V/I vs.I/I_(m)(I_(m) is the maximum value of Stokes I)curve to estimate the threshold of saturation,then reconstruct Stokes V/I in a strong field region to correct for saturation.The algorithm is demonstrated to be effective by comparing with the magnetograms obtained by the Helioseismic and Magnetic Imager(HMI).The accuracy rate of detection and correction for saturation is~99.4%and~88%respectively among 175 active regions.The advantages and disadvantages of the algorithm are discussed.

Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders:phase 1 trial interim results

Chimeric antigen receptor(CAR)T-cell therapy that targets B-cell maturation antigen(BCMA)have great potentials in autoimmune diseases and could be novel therapeutics for relapsed/refractory neuromyelitis optica spectrum disorder(NMOSD).To evaluate the safety and efficacy of the CT103A,a self-developed BCMA-targeting CAR construct against BCMA,in patients with AQP4-IgG seropositive NMOSD,an ongoing,investigator-initiated,open-label,single-arm,phase 1 clinical trial is conducted at our center.In total,12 patients were administered with a CAR-BCMA infusion.Ten of the 12 patients dosed were women(83.3%),with a median age of 49.5 years(range,30-67).were The most common events of grade 3 or higher were hematologic toxic effects.Seven patients(58%)developed infections,but no grade 4 infections occurred.Cytokine release syndrome was reported in all patients with only events of grade 1 or 2 observed.During the follow-up of a median 5.5 months,11 patients had no relapse;all patients generally reported improvement in disabilities and quality-of-life outcomes;11 patients’AQP-4 antibodies in serum showed a downward trend by the cutoff date.CAR T-cell expansion was associated with responses,and persisted more than 6 months post-infusion in 17%of the patients.In summary,CAR T-cell therapy shows a manageable safety profile and therapeutic potentials for patients with relapsed/refractory AQP4-IgG seropositive NMOSD.Another expansion phase is currently underway to determine the safety and efficacy of CAR T-BCMA infusion in patients with other neuro-inflammatory diseases.

PA-E18G substitution in influenza A virus confers resistance to ZX-7101,a cap-dependent endonuclease inhibitor

Cap-dependent endonuclease(CEN)in the polymerase acidic protein(PA)of influenza A virus(IAV)represents a promising drug target due to its critical role in viral gene transcription.The CEN inhibitor,baloxavir marboxil(BXM),was approved in Japan and the US in 2018 and several other countries subsequently.Along with the clinical use of BXM,the emergence and spread of IAV variants with reduced susceptibility to BXM have aroused serious concern.Herein,we comprehensively characterized the in vitro and in vivo antiviral activities of ZX-7101A,an analogue of BXM.The active form of prodrug ZX-7101 showed broad-spectrum antiviral potency against various IAV subtypes,including pH1N1,H3N2,H7N9 and H9N2,in MDCK cells,and the 50%effective concentration(EC_(50))was calculated to nanomole level and comparable to that of baloxavir acid(BXA),the active form of BXM.Furthermore,in vivo assays showed that administration of ZX-7101A conferred significant protection against lethal pH1N1 challenge in mice,with reduced viral RNA loads and alleviated pulmonary damage.Importantly,serial passaging of H1N1 virus in MDCK cells under selection pressure of ZX-7101 led to a resistant variant at the 15th passage.Reverse genetic and sequencing analysis demonstrated that a single E18G substitution in the PA subunit contributed to the reduced susceptibility to both ZX-7101 and BXA.Taken together,our results not only characterized a new CEN inhibitor of IAV but also identified a novel amino acid substitution responsible for CEN inhibitor resistance,which provides critical clues for future drug development and drug resistance surveillance.

An efficient synthesis of imidodicarbonic diamides from 1,3-thiazetidin-2-ones with NH_2OH·HCl via ring-opening reaction

A ring-opening process of 4-imino-1,3-thiazetidin-2-ones with NH2OH.HCI was described for the first time. Two different scaffolds of imidodicarbonic diamide were obtained selectively in good yields in the presence of organic base. The obtained imidodicarbonic diamides were demonstrated by X-ray diffraction analysis.

Molecular Epidemiology and Vaccine Compatibility Analysis of Seasonal Influenza Viruses in Wuhan, 2016–2019

Influenza viruses(FLUV)cause high morbidity and mortality annually in the world and pose a serious threat to the public health.Wuhan,as an important transportation hub in China,has a dense population and suitable climate,which also lays a major hidden danger for the outbreak of influenza.To survey and characterize the seasonal FLUV in Wuhan during 2016–2019,we collected 44,738 throat swabs,among which 15.5%were influenza A(FLUAV)positive,6.1%influenza B(FLUBV)and 0.3%co-infection.By monitoring FLUV in each month from June 2016 to May 2019,different with the previously seasonality pattern,only a single influenza peak was appeared in winter of 2017–2018 and 2018–2019,respectively.These data indicated that the complex circulation pattern of seasonal influenza in Wuhan.In addition,we found the age group was skewed towards 5–14 years group whose activity were mostly school based,which suggested school may be an important place for influenza outbreaks.Meanwhile,phylogenic analysis revealed that two subtypes(subclade 3C.2 a2 and 3C.2 a1b)of A(H3N2)were circulating in Wuhan and there was an obvious transition in 2018 because the two subclades were detected simultaneously.Furthermore,by estimating the vaccine effectiveness,we found that the vaccine strain of FLUAV didn’t seem to match very well the current epidemic strain,especially A(H3N2).Hence,more accurate prediction of seasonal outbreak is essential for vaccine design.Taken together,our results provided the current information about seasonal FLUV in Wuhan which form the basis for vaccine updating.

The infection kinetics and transmission potential of two Guaico Culex viruses in Culex quinquefasciatus mosquitoes

Guaico Culex virus(GCXV)is a newly identified segmented Jingmenvirus from Culex spp.mosquitoes in Central and South America.The genome of GCXV is composed of four or five single-stranded positive RNA segments.However,the infection kinetics and transmission capability of GCXV in mosquitoes remain unknown.In this study,we used reverse genetics to rescue two GCXVs(4S and 5S)that contained four and five RNA segments,respectively,in C6/36 cells.Further in vitro characterization revealed that the two GCXVs exhibited comparable replication kinetics,protein expression and viral titers.Importantly,GCXV RNAs were detected in the bodies,salivary glands,midguts and ovaries of Culex quinquefasciatus at 4–10 days after oral infection.In addition,two GCXVs can colonize Cx.quinquefasciatus eggs,resulting in positive rates of 15%–35%for the second gonotrophic cycle.In conclusion,our results demonstrated that GCXVs with four or five RNA segments can be detected in Cx.quinquefasciatus eggs during the first and second gonotrophic cycles after oral infection.