PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality

Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes.To further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male fertility.Furthermore,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells.Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−mice.Taken together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.

Efficacy of peripheral blood stem cell transplantation versus conventional chemotherapy on anaplastic large-cell lymphoma:a retrospective study of 64 patients from a single center

Anaplastic large-cell lymphoma(ALCL) is characterized by frequently presenting adverse factors at diagnosis.Many groups believed aggressive treatment strategies such as autologous stem cell transplantation brought survival benefit for ALCL patients.However,few compared these approaches with conventional chemotherapy to validate their superiority.Here,we report a study comparing the efficacy of peripheral blood stem cell transplantation(PBSCT) and conventional chemotherapy on ALCL.A total of 64 patients with primary systemic ALCL were studied retrospectively.The median follow-up period was 51 months(range,1-167 months).For 48 patients undergoing conventional chemotherapy only,the 4-year event-free survival(EFS) and overall survival(OS) rates were 70.7% and 88.3%,respectively.Altogether,16 patients underwent PBSCT,including 11 at first remission(CR1/PR1),3 at second remission,and 2 with disease progression during first-line chemotherapy.The 4-year EFS and OS rates for patients underwent PBSCT at first remission were 81.8% and 90.9%,respectively.Compared with conventional chemotherapy,PBSCT did not show superiority either in EFS(P = 0.240) or in OS(P = 0.580) when applied at first remission.Univariate analysis showed that patients with B symptoms(P = 0.001),stage III/IV disease(P = 0.008),bulky disease(P = 0.075),negative anaplastic lymphoma kinase(ALK) expression(P = 0.059),and age ≤ 60 years(P = 0.054) had lower EFS.Furthermore,PBSCT significantly improved EFS in patients with B symptoms(100% vs.50.8%,P = 0.027) or bulky disease(100% vs.52.8%,P = 0.045) when applied as an up-front strategy.Based on these results,we conclude that,for patients with specific adverse factors such as B symptoms and bulky disease,PBSCT was superior to conventional chemotherapy in terms of EFS.

A kinematic study of the integral shaped filament:what roles do filaments play in forming young stellar clusters?

Young protoclusters （embedded stellar clusters） are responsible for the vast majority of star formation currently occurring in the Galaxy. Recent observations suggest a scenario in which filamen-tary structures in the interstellar medium represent the first step towards precluster clumps and even- tually star formation. Whether filaments continuously fuel the star formation process when the cluster accretes material is still an open question. In this paper, we present a case study of the famous ＇integral shaped filament＇ （ISF） in the Orion A molecular cloud and we seek to study the kinematics which is truly originated from the ISF. We firstly define the central ridge of the ISF with NHa, ^12CO, ^13CO and N2H^＋. Undulations are present in all the ridges. Moreover, a large scale offset is apparent in the ridges as derived by different tracers, which may be explained by the slingshot mechanism proposed by Stutz ＆ Gould. We fit the velocity field of the ISF and find the derived velocity gradient is about 0.7 km s^- 1 pc^- 1 which may come from an overall contraction. We propose a method to check the accretion flow along the ISF by using the velocity deviations of different molecular tracers, which is better than the common method of using the velocity distribution of one tracer alone. Using the velocity deviations, we also find that OMC-1 to 5 are located close to the local extrema of the fluctuations, which may demonstrate that gas flows toward each clump along the ISE

Frequency dependence in the emission from subpulse drifting pulsars

We investigate relations in the emission properties as revealed by drifting subpulses detected at different observing frequencies based on the method that incorporates the rotating carousels in pulsar magnetospheres of multiple emission states.An emission state is associated with particular emission properties as determined by the drifting subpulses at a particular frequency,and different emission states obtained at different frequencies reveal the variation of emission properties across the emission region.The method allows the determination of the essential radio emission properties such as the relative emission height,subpulse number,charge density and the plasma flow relative to corotation in an emission region for a particular frequency.We apply the method to seven pulsars that exhibit subpulse drifting along single drift-band at 326 MHz and 1429 MHz.Our results show that drifting subpulses observed at different frequencies correspond to particular emission states suggesting that the pulsar emission properties are frequency dependent.We show that emission follows the frequency-to-radius mapping for pulsars with obliquity angle?30°regardless of the sign and magnitude of the drift-rate.For pulsars with long rotation periods in our sample,the circulation time for the plasma to revolve once around the magnetosphere relative to corotation increases as the rotation period increases at both frequencies,but exhibits irregularity for pulsars with short rotation periods.Our results suggest that evolution of the obliquity angles in subpulse drifting pulsars is from large to small,and the emission region tends to be’thicker’in younger pulsars.

1_(10)-1_(11) H_2CO and H_(110α) observations towards the giant HII region in cloud complex W43

The 110-111 formaldehyde （H2CO） absorption line and H110α radio recombination line （H RRL） are observed towards the giant HII region in cloud complex W43. The observations are obtained using the Nanshan 25 m single dish operated by Urumqi Observatory, National Astronomical Observatories of China. A region about 30 × 30 is observed, which covers the whole HII region in W43. Except for the central 10 region, all the other seven points are first observed with the H2CO 110-111 absorption. The column density of the H2CO is calculated, and the H2CO density contours show some differences with the infrared image. Multiple features appear in the H2CO and H RRL which indicate complex structure. The intensities of the H2CO and the velocities of the H110α seem to present a linear correlation, which illustrates that the sphere of influence of the central WR/OB cluster may be much more extended than presently known, since the size is nearly 50 pc.

Cycle performance studies on a new HFC-161/125/143a mixture as an alternative refrigerant to R404

In this paper, a new ternary non-azeotropic mixture of HFC-161/125/143a （0.15/0.45/0.40 in mass fraction）, as a promising mixed refrigerant to R404A, is presented. The ozone depletion potential （ODP） of the new refrigerant is zero and its basic thermodynamic properties are similar to those of R404A, but its global warming potential （GWP） is much smaller than those of R507A and R404A. Meanwhile, theoretical calculations show that, under the working condition 1 （the average evaporation temperature： -23℃, the average condensing temperature： 43℃, the superheat temperature： 28℃, the subcooling temperature： 5 ℃）, the volumetric refrigerating effect and specific refrigerating effect of the new mixture are 2.33% and 15.48% higher, re- spectively, than those of R404A. The coefficient of performance （COP） of the new mixture is 5.19% higher than that of R404A and the pressure ratio of the new mixture is 0.82% lower than that of R404A. Equally, under the working condition II （the average evaporation temperature： -40℃, the average condensing temperature： 35℃, the superheating temperature： 30 ~C, the subcooling temperature： 5℃）, the volumetric refrigerating effect and specific refrigerating effect of the new mixture are 2.24% and 20.58% higher, respectively, than those of R404A. The COP of the new mixture is 4.60% higher than that of R404A and the pressure ratio of the new mixture is similar to that of R404A. The performances of the new mixture and R404A are compared in a vapor compressor refrigeration apparatus originally designed for R404A under several working conditions （condensing temperatures： 35-45℃, evaporation temperatures： -40--20℃）. Experimental results show that the new mixture can obtain a higher COP, by 6.3% to 12.1%, and a lower pressure ratio, by 1.8% to 6.6%, compared to R404A; although the discharge temperature of the new mixture is slightly higher than that of R404A. The advantages of the new mixture will be further verified in the actual system.

Bendamustine treatment of Chinese patients with relapsed indolent non-Hodgkin lymphoma: a multicenter, open-label, single-arm, phase 3 study

Background:Bendamustine was approved in China on May 26th,2019 by the National Medical Product Administration for the treatment of indolent B-cell non-Hodgkin lymphoma(NHL).The current study was the registration trial and the first reported evaluation of the efficacy,safety,and pharmacokinetics of bendamustine in Chinese adult patients with indolent B-cell NHL following relapse after chemotherapy and rituximab treatment.Methods:This was a prospective,multicenter,open-label,single-arm,phase 3 study(NCT01596621;C18083/3076)with a 2-year follow-up period.Eligible patients received bendamustine hydrochloride 120 mg/m2 infused intravenously on days 1 and 2 of each 21-day treatment cycle for at least six planned cycles(and up to eight cycles).The primary endpoint was the overall response rate(ORR);and secondary endpoints were duration of response(DoR),progression-free survival(PFS),safety,and pharmacokinetics.Patients were classified according to their best overall response after initiation of therapy.Proportions of patients in each response category(complete response[CR],partial response[PR],stable disease,or progressive disease)were summarized along with a twosided binomial exact 95%confidence intervals(CIs)for the ORR.Results:A total of 102 patients were enrolled from 20 centers between August 6th,2012,and June 18th,2015.At the time of the primary analysis,the ORR was 73%(95%CI:63%–81%)per Independent Review Committee(IRC)including 19%CR and 54%PR.With the follow-up period,the median DoR was 16.2 months by IRC and 13.4 months by investigator assessment;the median PFS was 18.6 months and 15.3 months,respectively.The most common non-hematologic adverse events(AEs)were gastrointestinal toxicity,pyrexia,and rash.Grade 3/4 neutropenia was reported in 76%of patients.Serious AEs were reported in 29 patients and five patients died during the study.Pharmacokinetic analysis indicated that the characteristics of bendamustine and its metabolites M3 and M4 were generally consistent with those reported for other ethnicities.Conclusion:Bendamustine is an active and effective therapy in Chinese patients with relapsed,indolent B-cell NHL,with a comparable risk/benefit relationship to that reported in North American patients.