Real-world evidence on treatment pattern, effectiveness, and safety of blinatumomab in Chinese patients with B-cell acute lymphoblastic leukemia.

Blinatumomab is efficacious in patients with B-cell acute lymphoblastic leukemia (B-ALL), yet limited real-world data exists in this context. This retrospective study provided real-world data on the treatment pattern, effectiveness, and safety of blinatumomab in Chinese patients with newly diagnosed (ND) and relapsed/refractory (R/R) B-ALL. Patients with B-ALL who received at least one dose of blinatumomab in frontline or R/R settings between August 2021 and June 2023 were included. The primary outcome was the treatment pattern of blinatumomab. Key secondary outcomes included complete remission (CR)/CR with incomplete blood cell recovery (CRi) rate, minimal residual disease (MRD) negativity, median event-free survival (EFS), and safety. The study included 96 patients with B-ALL; 53 (55.2%) patients were in the ND group and 43 (44.8%) patients were in the R/R group. The median treatment duration was one cycle (range: 1-5). Most patients underwent chemotherapies, allo-HSCT, or experimental CAR-T following blinatumomab. The ND patients using blinatumomab induction therapy achieved 100% CR/CRi rate; 87.2% achieved MRD negativity within two cycles of blinatumomab. In R/R re-induction patients, the CR/CRi rate was 50%; MRD negativity rate was 64.2%. In R/R patients using blinatumomab for consolidation, MRD negativity rate was 90.9%. The median EFS was not reached in both ND and R/R patients; 1-year EFS rate was 90.8% (95% CI: 67%, 97%) and 55.1% (95% CI: 30%, 74%), respectively. Grade ≥ 3 adverse events were observed in 12.5% patients. Blinatumomab was found to be effective with a tolerable safety profile in real world setting.

The prevalence of Human Immunodeficiency Virus infection among voluntary blood donors in mainland China: A systematic review and meta-analysis.

Human immunodeficiency virus (HIV) infection through transfusion has been an imperative challenge for blood safety. Despite the implementation of screening strategies, there was still the residual risk of transfusion-transmitted HIV. Considering that the prevalence of HIV infection in blood donors is significant for evaluating blood safety and potential risks to the population, meta-analysis was applied to investigate the HIV prevalence among voluntary blood donors during the past 27 years to characterize the epidemiology and related risk factors of HIV in blood donors. The literature concerning the HIV screening reactive rate and prevalence in Chinese voluntary blood donors was collected through the systematic searching of four electronic databases. After integrating data, following the Preferred Reporting of Items for Systematic Reviews and Meta-Analyses guidelines, data manipulation and statistical analyses were conducted by Stata 12.0. The results indicated that overall HIV prevalence was 0.0178% (95% confidence interval [CI], 0.0169%-0.0187%) with a remarkable rise, which varied from 2000 (0.0034%) to 2015 (0.027%). The HIV window period infection rate was 0.0475‱ (95% CI, 0.0304‱-0.0646‱). Importantly, subgroup analysis revealed the heterogeneity in gender, occupations, education and donation frequency. With the effective control of HIV transmission through blood, HIV prevalence declined in China to some extent in recent years, and the characteristics of HIV epidemic in some provinces have drastically changed. However, remaining relatively high HIV prevalence and overall increased trend of HIV prevalence since the 21th century demonstrates the potential residual risk of blood transfusion, and the whole society is supposed to pay close attention to HIV infection.

Endophytic Bacillus pumilus G5 Interacting with Silicon to Improve Drought Stress Resilience in Glycyrrhiza uralensis Fisch. by Modulating Nitrogen Absorption, Assimilation, and Metabolism Pathways.

Drought stress has become the primary severe threat to global agriculture production, including medicinal plants. Plant growth-promoting bacteria (PGPB) and environmentally friendly element silicon (Si) have emerged as effective methods in alleviating drought stress in various plants. Here, the effects of the plant endophytic G5 interaction with Si on regulating nitrogen absorption, assimilation, and metabolism pathways were investigated in the morphophysiological and gene attributes of Glycyrrhiza uralensis exposed to drought. Results showed that G5+Si application improved nitrogen absorption and assimilation by increasing the available nitrogen content in the soil, further improving the nitrogen utilization efficiency. Then, G5+Si triggered the accumulation of the major adjustment substances proline, γ-aminobutyric acid, putrescine, and chlorophyll, which played an important role in contributing to maintaining balance and energy supply in G. uralensis exposed to drought. These findings will provide new ideas for the combined application of PGPR and Si on both soil and plant systems in a drought habitat.

Wireless-Channel Key Distribution Based on Laser Synchronization.

We propose and experimentally demonstrate a wireless-channel key distribution scheme based on laser synchronization induced by a common wireless random signal. Two semiconductor lasers are synchronized under injection of the drive signal after electrical-optical conversion and emit irregular outputs that are used to generate shared keys. Our proof-of-concept experiment using a complex drive signal achieved a secure key generation rate of up to 150 Mbit/s with a bit error rate below 3.8 × 10-3. Numerical simulation results show that the proposed scheme has the potential to achieve a distribution distance of several hundred meters. It is believed that common-signal-induced laser synchronization paves the way for high-speed wireless physical-layer key distribution.

Enhancing Magnetic Damping under GaAs Band-Edge Photoexcitation in a Co2FeAl/n-GaAs Heterojunction.

The ultrafast manipulation of spin in ferromagnet-semiconductor (FM/SC) heterojunctions is a key issue for advancing spintronics, where magnetic damping and interfacial spin transport often define device efficiency. Leveraging selective optical excitation in semiconductors offers a unique approach to spin manipulation in FM/SC heterojunctions. Herein, we investigated the magnetic dynamics of a Co2FeAl/n-GaAs heterojunction using the time-resolved magneto-optical Kerr technique and observed the considerably enhanced magnetic damping of Co2FeAl when GaAs is photoexcited near its band edge. This enhancement is attributed to an enhanced spin-pumping effect facilitated by spin-dependent carrier tunneling and capture within the Co2FeAl layer. Moreover, circularly polarized light excites spin-polarized band-edge photocarriers, further impacting the magnetic damping of Co2FeAl through an additional optical spin-transfer torque on the magnetic moment of Co2FeAl. Our results provide a valuable reference for manipulating spin-pumping and interfacial spin transport in FM/SC heterojunctions, showcasing the advantage of optical control of semiconductor photocarriers for the ultrafast manipulation of magnetic dynamics and interfacial spin transfer.

Bacillus cereus G2 alleviate salt stress in Glycyrrhiza uralensis Fisch. by balancing the downstream branches of phenylpropanoids and activating flavonoid biosynthesis.

The salinity environment is one of the biggest threats to Glycyrrhiza uralensis Fisch. (G. uralensis) growth, resulting from the oxidative stress caused by excess reactive oxygen species (ROS). Flavonoids are the main pharmacodynamic composition and help maintain ROS homeostasis and mitigate oxidative damage in G. uralensis in the salinity environment. To investigate whether endophytic Bacillus cereus G2 can improve the salt-tolerance of G. uralensis through controlling flavonoid biosynthesis, the transcriptomic and physiological analysis of G. uralensis treated by G2 in the saline environment was conducted, focused on flavonoid biosynthesis-related pathways. Results uncovered that salinity inhibited flavonoids synthesis by decreasing the activities of phenylalanine ammonialyase (PAL) and 4-coumarate-CoA ligase (4CL) (42% and 39%, respectively) due to down-regulated gene Glyur000910s00020578 at substrate level, and then decreasing the activities of chalcone isomerase (CHI) and chalcone synthase (CHS) activities (50% and 42%, respectively) due to down-regulated genes Glyur006062s00044203 and Glyur000051s00003431, further decreasing isoliquiritigenin content by 53%. However, salt stress increased liquiritin content by 43%, which might be a protective mechanism of salt-treated G. uralensis seedlings. Interestingly, G2 enhanced PAL activity by 27% whereas reduced trans-cinnamate 4-monooxygenase (C4H) activity by 43% which could inhibit lignin biosynthesis but promote flavonoid biosynthesis of salt-treated G. uralensis at the substrate level. G2 decreased shikimate O-hydroxycinnamoyltransferase (HCT) activity by 35%, increased CHS activity by 54% through up-regulating the gene Glyur000051s00003431 encoding CHS, and increased CHI activity by 72%, thereby decreasing lignin (34%) and liquiritin (24%) content, but increasing isoliquiritigenin content (35%), which could mitigate oxidative damage and changed salt-tolerance mechanism of G. uralensis.

Biocompatible formulation of a hydrophobic antimicrobial peptide L30 through nanotechnology principles and its potential role in mouse pneumonia model infected with Staphylococcus aureus.

Hydrophobic antimicrobial peptide L30, a potential antibiotic candidate, has poor water solubility and hemolytic activity. Herein, a biocompatible nano-formulation composed of liposomes and dendritic mesoporous silica encapsulation (LDMSNs@L30) was constructed for L30 to solve the limits for its clinical development. The characterization, antimicrobial activity and therapeutic effect of LDMSNs@L30 on Staphylococcus aureus 9 (cfr+) infected mice models were investigated. LDMSNs@L30 displayed a smooth, spherical, and monodisperse nanoparticle with a hydrodynamic diameter of 177.40 nm, an encapsulation rate of 56.13%, a loading efficiency of 32.26%, a release rate of 66.5%, and effective slow-release of L30. Compared with free L30, the formulation could significantly increase the solubility of L30 in PBS with the maximum concentration from 8 µg/mL to 2.25 mg/mL and decrease the hemolytic activity of hydrophobic peptide L30 with the HC5 from 65.36 µg/mL to more than 500 µg/mL. The nano delivery system LDMSNs@L30 also exhibited higher therapeutic effects on mice models infected with S. aureus 9 (cfr+) than those of free L30 after 7 days of treatment by reducing the lung inflammation and the inflammatory cytokines levels in plasma, showing better health score and pulmonary pathological improvement. Our research suggests that nano-formulation can be expected to be a promising strategy for peptide drugs in therapeutic applications.

The chemokine CCL20 can assist AFP in serological diagnosis of hepatocellular carcinoma.

The chemokine 20 (CCL20) is a member of the CC chemokine family and plays a role in tumor immunity and autoimmune disease. This work investigated the value of CCL20 as a serum diagnostic marker for primary hepatocellular carcinoma (HCC). Based on the data of hepatocellular carcinoma patients in the TCGA database, the up-regulated genes encoding secretory proteins were analyzed in each pathological stage, and the candidate marker CCL20 gene was selected. Serum concentrations of CCL20 in patients with primary HCC, benign liver disease, and healthy subjects were analyzed by enzyme-linked immunosorbent assay (ELISA). The ROC curve evaluated the efficacy of CCL20 alone or in combination with AFP in the diagnosis of HCC. It was found the expression of CCL20 in HCC patients was significantly higher than that in the benign liver disease group and healthy controls (P < 0.05); The AUC of ROC curve to distinguish HCC patients from healthy controls was 0.859, the sensitivity was 73.42%, and the specificity was 86.84%. After combination with AFP, the AUC increased to 0.968, the sensitivity was 88.16%, and the specificity was 97.37%. Although CCL20 was increased in the serum of patients with benign liver diseases, combined with AFP, the AUC to distinguish HCC patients from non-HCC cohorts (benign liver disease group and healthy control group) was 0.902, with a sensitivity of 91.67% and a specificity of 75.26%. Collectively, serum CCL20 is closely related to the occurrence of HCC, and detection of serum CCL20 can assist AFP in improving the diagnostic sensitivity of HCC.

Low-Temperature Growth of InGaAs Quantum Wells Using Migration-Enhanced Epitaxy.

The growth of InGaAs quantum wells (QWs) epitaxially on InP substrates is of great interest due to their wide application in optoelectronic devices. However, conventional molecular beam epitaxy requires substrate temperatures between 400 and 500 °C, which can lead to disorder scattering, dopant diffusion, and interface roughening, adversely affecting device performance. Lower growth temperatures enable the fabrication of high-speed optoelectronic devices by increasing arsenic antisite defects and reducing carrier lifetimes. This work investigates the low-temperature epitaxial growth of InAs/GaAs short-period superlattices as an ordered replacement for InGaAs quantum wells, using migration-enhanced epitaxy (MEE) with low growth temperatures down to 200-250 °C. The InAs/GaAs multi-quantum wells with InAlAs barriers using MEE grown at 230 °C show good single crystals with sharp interfaces, without mismatch dislocations found. The Raman results reveal that the MEE mode enables the growth of (InAs)4(GaAs)3/InAlAs QWs with excellent periodicity, effectively reducing alloy scattering. The room temperature (RT) photoluminescence (PL) measurement shows the strong PL responses with narrow peaks, revealing the good quality of the MEE-grown QWs. The RT electron mobility of the sample grown in low-temperature MEE mode is as high as 2100 cm2/V∗s. In addition, the photoexcited band-edge carrier lifetime was about 3.3 ps at RT. The high-quality superlattices obtained confirm MEE's effectiveness for enabling advanced III-V device structures at reduced temperatures. This promises improved performance for applications in areas such as high-speed transistors, terahertz imaging, and optical communications.

Migration-Enhanced Epitaxial Growth of InAs/GaAs Short-Period Superlattices for THz Generation.

The low-temperature-grown InGaAs (LT-InGaAs) photoconductive antenna has received great attention for the development of highly compact and integrated cheap THz sources. However, the performance of the LT-InGaAs photoconductive antenna is limited by its low resistivity and mobility. The generated radiated power is much weaker compared to the low-temperature-grown GaAs-based photoconductive antennas. This is mainly caused by the low abundance of excess As in LT-InGaAs with the conventional growth mode, which inevitably gives rise to the formation of As precipitate and alloy scattering after annealing. In this paper, the migration-enhanced molecular beam epitaxy technique is developed to grow high-quality (InAs)m/(GaAs)n short-period superlattices with a sharp interface instead of InGaAs on InP substrate. The improved electron mobility and resistivity at room temperature (RT) are found to be 843 cm2/(V·s) and 1648 ohm/sq, respectively, for the (InAs)m/(GaAs)n short-period superlattice. The band-edge photo-excited carrier lifetime is determined to be ~1.2 ps at RT. The calculated photocurrent intensity, obtained by solving the Maxwell wave equation and the coupled drift-diffusion/Poisson equation using the finite element method, is in good agreement with previously reported results. This work may provide a new approach for the material growth towards high-performance THz photoconductive antennas with high radiation power.

Genome-Wide Identification, Sequence Alignment, and Transcription of Five Sex-Related Genes in Largemouth Bass (Micropterus Salmoides).

BACKGROUND: Largemouth bass (Micropterus Salmoides) is an economically important fish species in China. Most research has focused on its growth, disease resistance, and nutrition improvement. However, the sex-determining genes in largemouth bass are still unclear. The transforming growth factor-beta (TGF-ß) gene family, including amh, amhr2 and gsdf, plays an important role in the sex determination and differentiation of various fishes. These genes are potentially involved in sex determination in largemouth bass. METHODS: We performed a systematic analysis of 5 sex-related genes (amh, amhr2, gsdf, cyp19a1, foxl2) in largemouth bass using sequence alignment, collinearity analysis, transcriptome, and quantitative real-time polymerase chain reaction (qRT-PCR). This included a detailed assessment of their sequences, gene structures, evolutionary traits, and gene transcription patterns in various tissues including gonads, and at different developmental stages. RESULTS: Comparative genomics revealed that the 5 sex-related genes were highly conserved in various fish genomes. These genes did not replicate, mutate or lose in largemouth bass. However, some were duplicated (amh, amhr2 and gsdf), mutated (gsdf) or lost (amhr2) in other fishes. Some genes (e.g., gsdf) showed significant differences in genomic sequence between males and females, which may contribute to sex determination and sex differentiation in these fishes. qRT-PCR was applied to quantify transcription profiling of the 5 genes during gonadal development and in the adult largemouth bass. Interestingly, amh, amhr2 and gsdf were predominantly expressed in the testis, while cyp19a1 and foxl2 were mainly transcribed in the ovary. All 5 sex-related genes were differentially expressed in the testes and ovaries from the 56th day post-fertilization (dpf). We therefore speculate that male/female differentiation in the largemouth bass may begin at this critical time-point. Examination of the transcriptome data also allowed us to screen out several more sex-related candidate genes. CONCLUSIONS: Our results provide a valuable genetic resource for investigating the physiological functions of these 5 sex-related genes in sex determination and gonadal differentiation, as well as in the control of gonad stability in adult largemouth bass.

Chickpea-Derived Modified Antimicrobial Peptides KTA and KTR Inactivate Staphylococcus aureus via Disrupting Cell Membrane and Interfering with Peptidoglycan Synthesis.

The widespread bacterial contamination caused by foodborne pathogens has continuously driven the development of advanced and potent food antimicrobial agents. In this study, two novel antimicrobial peptides (AMPs) named KTA and KTR were obtained by modifying a natural AMP, Leg2, from chickpea storage protein legumin hydrolysates. They were further predicted to be stable hydrophobic cationic AMPs of α-helical structure with no hemolytic toxicity by several online servers. Moreover, the AMPs exerted superior antibacterial activity against two representative Staphylococcus aureus strains thanks to the increased hydrophobicity and positive charge, with minimum inhibition concentration value (4.74-7.41 µM) significantly lower than that of Leg2 (>1158.70 µM). Further, this study sought to elucidate the specific antimicrobial mechanism against Gram-positive bacteria. It was found that the electrostatic interactions of the AMPs with peptidoglycan were vital for peptide activity in combating Gram-positive bacteria. Subsequently, the cell membrane of S. aureus cells was irreversibly disrupted by increasing permeability and impairing membrane components, which led to the massive release of intracellular substances and eventual cell death. Overall, this work demonstrated that KTA and KTR were active against Gram-positive bacteria via peptidoglycan targeting and membrane-disruptive mechanisms and paved the way for expanding their application potential to alleviate food contamination.

Ultrasonically functionalized chitosan-gallic acid films inactivate Staphylococcus aureus through envelope-disruption under UVA light exposure.

The significant threat of foodborne pathogens contamination has continuously promoted the development of efficient antimicrobial food packaging materials. Here, an antimicrobial film was prepared with gallic acid-grafted-chitosan (CS/GA) that obtained by a two-step ultrasound method. The resultant films exhibited good transparency, improved UV barrier performance, and enhanced mechanical strength. Specifically, with the grafting of 1.2 % GA, the UV blocking ability of CS/GA film at 400 nm was significantly increased by 19.7 % and the tensile strength was nearly two times higher than that of CS film. Moreover, the CS/GA films exhibited an inspiring photoactivated bactericidal ability under 400 nm UVA light irradiation that eradicated almost 99.9 % of Staphylococcus aureus (S. aureus) cells within 60 min. To gain more insights into the antibacterial mechanism, the treated S. aureus cells were further investigated by visualizing bacterial ultrastructure and analyzing membrane properties. The results pointed to the peptidoglycan layer as the primary action target when bacteria come into contact with CS/GA films. Afterward, the intracellular oxidative lesions, disrupted bacterial integrity, and disordered membrane functional properties collectively resulted in eventual cell death. The findings revealed the unique peptidoglycan targeting and membrane disruptive mechanisms of CS/GA films, confirming the application values in controlling foodborne pathogens.

Burnout, moral injury, and suicidal/self-harm ideation among healthcare professionals in Mainland China: Insights from an online survey during the COVID-19 pandemic.

OBJECTIVE: This survey aimed to explore the relationships between burnout, moral injury, and suicidal/self-harm ideation among Chinese health professionals to provide a reference for protecting their mental health. METHOD: Health professionals were surveyed online using the Maslach Burnout Inventory-Human Services Survey for Medical Personnel, Patient Health Questionnaire-9, and the Moral Injury Symptoms Scale-Health Professional. RESULTS: In the analysis, 6146 eligible respondents were included in the study. The average participant age was 34.9 ± 8.5 years, and suicidal/self-harm ideation was detected in 2338 participants (38.0%). The prevalence of suicidal/self-harm ideation among those with severe burnout in the dimensions of emotional exhaustion, depersonalisation, and decreased personal accomplishment was significantly higher than those with mild burnout. The prevalence of suicidal/self-harm ideation among those with significant moral injury symptoms was higher than those without moral injury. Unconditional logistic regression analysis showed that those with moderate or severe emotional exhaustion, moderate or severe reduced sense of professional accomplishment and moderate or severe depersonalisation had increased risks of suicidal/self-harm ideation. CONCLUSIONS: Structural equation modelling demonstrated that burnout significantly mediated the relationship between moral injury and suicidal/self-harm ideation. The proportion of mediation (PM) by burnout was 43.0%. Burnout and moral injury were potential predictors of suicidal/self-harm ideation among health professionals. Both moral injury and burnout had positive and direct effects on suicidal/self-harm ideation, and burnout was a mediator in this relationship among Chinese health professionals. Therefore, to alleviate the moral injury and subsequent burnout of healthcare workers and enhance their mental qualities, active interventions should be developed in the future.

Security optimization of synchronization in DFB lasers under constant-amplitude random-phase drive light by reducing drive-response correlation.

Common-signal-induced laser synchronization promoted a promising paradigm of high-speed physical key distribution. Constant-amplitude and random-phase (CARP) light was proposed as the common drive signal to enhance security by reducing the correlation between the drive and the laser response in intensity. However, the correlation in light phase is not examined. Here, we numerically reveal that the correlation coefficient of the CARP light phase and the response laser intensity (denoted as CCR-φD) can reach a value close to 0.6. Effects of parameters including optical frequency detuning, and modulation depth and noise bandwidth and transparency carrier density for CARP light generation are investigated in detail. By optimizing the optical frequency, modulation depth, and noise bandwidth, respectively, CCR-φD can be reduced to 0.32, 0.18, and 0.10. In the meantime, CCR-φD can be further reduced through secondary optimizing of parameters. CCR-φD can be further reduced by increasing transparent carrier density provided response laser synchronization is achieved. This work gives a new insight about the laser synchronization induced by common CARP light, and also contributes a suggestion of security improvement for physical key distribution based on laser synchronization.

A Systematic Review and Meta-analysis of Renin-angiotensin Inhibitors and Angiotensin Receptor Neprilysin Inhibitors in Preventing Recurrence after Atrial Fibrillation Ablation.

To systematically evaluate the efficacy and safety of renin-angiotensin inhibitors (RASIs) and angiotensin receptor neprilysin inhibitors (ARNI) in preventing the recurrence of atrial fibrillation after atrial fibrillation ablation, we have written this meta-analysis. We systematically searched randomized controlled trials or cohort studies on renin-angiotensin inhibitors and angiotensin receptor neprilysin inhibitor-Sacubitril/Valsartan (SV) in preventing the recurrence of atrial fibrillation. Two researchers independently screened the literature, extracted the data, and assessed the risk of bias in the included studies. Afterward, the meta-analysis was performed using RevMan 5.3 software. This meta-analysis results showed that the recurrence rate of atrial fibrillation after ablation in subjects using renin-angiotensin inhibitors (RASIs) was lower than in subjects not using them [RR = 0.85, 95%CI (0.72, 0.99), P = 0.03]; the recurrence rate in subjects using Sacubitril/Valsartan (SV) was lower than in subjects using renin-angiotensin inhibitors (RASIs) [RR= 0.50, 95%CI (0.37, 0.68), P < 0.00001]. These results show that both the use of renin-angiotensin inhibitors (RASIs) and Sacubitril/Valsartan (SV) can prevent the recurrence of after atrial fibrillation ablation, among which the use of Sacubitril/Valsartan (SV) is more effective.

Chaos synchronization of VCSELs with common injection of polarization-random light.

We propose and numerically demonstrate chaos synchronization of two vertical-cavity surface-emitting lasers (VCSELs) induced by common injection of constant-amplitude random-polarization light for physical key distribution. Results show that synchronization is sensitive to polarization rotation of injection light, and synchronization coefficients larger than 0.9 can be achieved as the rotation-degree mismatch is smaller than ±10°. Therefore, polarization rotation degree can serve as a hardware key parameter. Furthermore, each laser's output has no correlation to the constant amplitude of the injected light. Their components with identical polarization state, e.g. x or y polarization of VCSEL, also have low correlation coefficient smaller than 0.2. It is therefore believed that this synchronization scheme can provide a security-enhanced method of physical key distribution.

RNA sequencing profiles reveals progressively reduced spermatogenesis with progression in adult cryptorchidism.

Introduction: The fertility of cryptorchidism patients who didn't perform corrective surgery will decrease with age. Herein, we elucidate the histological alterations and underlying molecular mechanism in patients with an increase in the disease duration from 20 to 40 years. Methods: Testicular tissues were obtained from three patients with cryptorchidism, ranging in age from 22 to 44 years. Three benign paracancerous testicular samples of matched ages were used as controls. The normal and undescended testicular tissues were stained with hematoxylin and eosin (HE) and immunofluorescence and all six testicular samples were subjected to RNA sequencing. RNA sequencing data were subjected to gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI) network analysis, and Gene Ontology (GO) searches. Real-time reverse transcriptase polymerase chain reaction was used to confirm the DEGs. Results: The seminiferous tubules' basement membrane thickens with age in healthy testes. As the period of cryptorchidism in the cryptorchid testis extended, the seminiferous tubules significantly atrophy, the number of spermatogenic cells declines, and the amount of interstitial fibrous tissue increases in comparison to normal tissues. The number of germ cells per cross-section of seminiferous tubules was significantly lower in cryptorchidism than in normal testicular tissues, according to immunofluorescence staining, but the number of Sertoli cells remained stable. RNA sequencing analysis identified 1150 differentially expressed genes (DEGs) between cryptorchidism and normal testicular tissues (fold change >2 and p<0.05), of which 61 genes were noticeably upregulated and 1089 were significantly downregulated. These genes were predominantly linked to sperm development and differentiation, and fertilization, according to GO analysis. Meiosis pathways were significantly downregulated in cryptorchidism, according to KEGG pathway analysis and GSEA (P<0.001). PPI analysis was used to identify the top seven downregulated hub genes (PLCZ1, AKAP4, IZUMO1, SPAG6, CAPZA3, and ROPN1L), which were then further verified by qPCR. Discussion: By describing the histological changes and differential gene expression patterns in adult cryptorchid patients of different age groups, we discovered the progression mechanisms of undescended testes in adults with aging and identified seven significantly downregulated hub genes (PLCZ1, AKAP4, IZUMO1, SPAG6, CAPZA3, and ROPN1L) in cryptorchid testis compared to normal testicular tissues. These genes played a role in the process of spermgenesis and are directly linked to the steady decline in fertility caused by cryptorchidism. Our study provided a better understanding of the molecular mechanisms underlying the loss of spermatogenesis in adult cryptorchidism, and give support for the development of adult cryptorchidism treatments.

Novel ADAMTS13 mutations in a patient with congenital thrombotic thrombocytopenic purpura.

Congenital thrombotic thrombocytopenic purpura (TTP) is a rare autosomal recessive genetic disorder caused by mutations in the ADAMTS13 gene. Approximately 200 mutations of the ADAMTS-13 gene have been identified, although only a few have been characterized through in vitro expression studies. We conducted an investigation on a male congenital TTP patient with reduced plasma levels of ADAMTS13 activity. DNA sequence analysis revealed two mutations on chromosome 9 (1.9q34.2) in the patient's ADAMTS13 gene. One mutation was a non-synonymous mutation (exon 5: c.A530G: p.Y177C), while the other was a nonsense mutation (exon 21: c.G2651A: p.W884X). Both mutations were found to be heterozygous. The patient's parents had no history of thrombocytopenia or neurological symptoms. DNA sequence analysis showed the patient's father was a heterozygote for the nonsense mutation of the ADAMTS13 gene (exon 21: c.G2651A: p.W884X), while the mother was a heterozygote for the non-synonymous mutation of the ADAMTS13 gene (exon 5: c.A530G: p.Y177C). To investigate the mechanism behind ADAMTS13 deficiency in this patient, wild type (WT), ADAMTS13 p.Y177C, and ADAMTS13 p.W884X were transiently expressed in 293-6E cells. Expression studies revealed a significant reduction in enzyme activity and secretion, although the protease was detected within the cells. The 3D structures of the natural and mutated ADAMTS-13 proteins were partially reconstructed using the Phyre2 web server. The mutation that replaces the tyrosine residue at amino acid position 177 with cysteine may result in decreased steric hindrance and a looser structure. This mutation affects the binding of calcium ions and the secretion of the enzyme from intracellular to extracellular compartments.

Bacillus cereus G2 Facilitates N Cycle in Soil, Further Improves N Uptake and Assimilation, and Accelerates Proline and Glycine Betaine Metabolisms of Glycyrrhiza uralensis Subjected to Salt Stress.

Soil salinity is a severe abiotic stress that reduces crop productivity. Recently, there has been growing interest in the application of microbes, mainly plant-growth-promoting bacteria (PGPB), as inoculants for saline land restoration and plant salinity tolerance. Herein, the effects of the plant endophyte G2 on regulating soil N cycle, plant N uptake and assimilate pathways, proline and glycine betaine biosynthesis, and catabolic pathways were investigated in Glycyrrhiza uralensis exposed to salinity. The results indicated that G2 improved the efficiency of N absorption and assimilation of plants by facilitating soil N cycling. Then, G2 promoted the synthesis substrates of proline and glycine betaine and accelerated its synthesis rate, which increased the relative water content and reduced the electrolyte leakage, eventually protecting the membrane system caused by salt stress in G. uralensis. These findings will provide a new idea from soil to plant systems in a salinity environment.