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Abstract The downregulation of Cadm4 (Cell adhesion molecular 4) is a prominent feature in demyelination diseases, yet, the underlying molecular mechanism remains elusive. Here, we reveal that Cadm4 undergoes specific palmitoylation at cysteine-347 (C347), which is crucial for its stable localization on the plasma membrane (PM). Mutation of C347 to alanine (C347A), blocking palmitoylation, causes Cadm4 internalization from the PM and subsequent degradation. In vivo experiments introducing the C347A mutation (Cadm4-KI) lead to severe myelin abnormalities in the central nervous system (CNS), characterized by loss, demyelination, and hypermyelination. We further identify ZDHHC3 (Zinc finger DHHC-type palmitoyltransferase 3) as the enzyme responsible for catalyzing Cadm4 palmitoylation. Depletion of ZDHHC3 reduces Cadm4 palmitoylation and diminishes its PM localization. Remarkably, genetic deletion of ZDHHC3 results in decreased Cadm4 palmitoylation and defects in CNS myelination, phenocopying the Cadm4-KI mouse model. Consequently, altered Cadm4 palmitoylation impairs neuronal transmission and cognitive behaviors in both Cadm4-KI and ZDHHC3 knockout mice. Importantly, attenuated ZDHHC3-Cadm4 signaling significantly influences neuroinflammation in diverse demyelination diseases. Mechanistically, we demonstrate the predominant expression of Cadm4 in the oligodendrocyte lineage and its potential role in modulating cell differentiation via the WNT-β-Catenin pathway. Together, our findings propose that dysregulated ZDHHC3-Cadm4 signaling contributes to myelin abnormalities, suggesting a common pathological mechanism underlying demyelination diseases associated with neuroinflammation.

Abstract Background In the cultural milieu of China, family caregivers assume a pivotal role in the post-adolescent suicide attempt recovery journey. Nevertheless, they frequently encounter a dearth of requisite knowledge and information pertaining to the appropriate caregiving protocols for these adolescents. Notwithstanding, scholarly investigation into the informational requisites of this demographic concerning caregiving remains significantly constrained. Methods Between September and December 2023, a phenomenological approach was applied in qualitative research. Semi-structured interviews were undertaken with 15 family caregivers of adolescents who had experienced suicide attempts. The amassed data underwent systematic organization and analysis through the utilization of the Colaizzi method. Results Four primary themes were identified: (1) negative emotional encounters; (2) requirements for addressing dilemmas; (3) addressing the needs of the unknown; and (4) insufficient access to support. Conclusions Family caregivers experience complex negative emotions upon learning about a teenager’s suicide attempt. Throughout the caregiving process, they face numerous challenges, with apparent lack of external support, leading to an increased urgent need for caregiving information. Healthcare professionals, especially nurses, should actively identify and respond to the informational needs of family caregivers when caring for adolescents who have attempted suicide. This includes providing education on various coping mechanisms and support strategies, as well as assisting them in better understanding how to effectively manage the stress and challenges of caregiving. By doing so, healthcare professionals can help alleviate the psychological and emotional burden on family caregivers, thereby enhancing their caregiving abilities and overall well-being.

Abstract The electrical outputs of single-layer antiferromagnetic memory devices relying on the anisotropic magnetoresistance effect are typically rather small at room temperature. Here we report a new type of antiferromagnetic memory based on the spin phase change in a Mn-Ir binary intermetallic thin film at a composition within the phase boundary between its collinear and noncollinear phases. Via a small piezoelectric strain, the spin structure of this composition-boundary metal is reversibly interconverted, leading to a large nonvolatile room-temperature resistance modulation that is two orders of magnitude greater than the anisotropic magnetoresistance effect for a metal, mimicking the well-established phase change memory from a quantum spin degree of freedom. In addition, this antiferromagnetic spin phase change memory exhibits remarkable time and temperature stabilities, and is robust in a magnetic field high up to 60 T.

Abstract Background Discrepancies in the utilization of reactive oxygen species (ROS) between cancer cells and their normal counterparts constitute a pivotal juncture for the precise treatment of cancer, delineating a noteworthy trajectory in the field of targeted therapies. This phenomenon is particularly conspicuous in the domain of nano-drug precision treatment. Despite substantial strides in employing nanoparticles to disrupt ROS for cancer therapy, current strategies continue to grapple with challenges pertaining to efficacy and specificity. One of the primary hurdles lies in the elevated levels of intracellular glutathione (GSH). Presently, predominant methods to mitigate intracellular GSH involve inhibiting its synthesis or promoting GSH efflux. However, a conspicuous gap remains in the absence of a strategy capable of directly and efficiently clearing GSH. Methods We initially elucidated the chemical mechanism underpinning oridonin, a diminutive pharmacological agent demonstrated to perturb reactive oxygen species, through its covalent interaction with glutathione. Subsequently, we employed the incorporation of maleimide-liposomes, renowned for their capacity to disrupt the ROS delivery system, to ameliorate the drug’s water solubility and pharmacokinetics, thereby enhancing its ROS-disruptive efficacy. In a pursuit to further refine the targeting for acute myeloid leukemia (AML), we harnessed the maleic imide and thiol reaction mechanism, facilitating the coupling of Toll-like receptor 2 (TLR2) peptides to the liposomes’ surface via maleic imide. This strategic approach offers a novel method for the precise removal of GSH, and its enhancement endeavors are directed towards fortifying the precision and efficacy of the drug’s impact on AML targets. Results We demonstrated that this peptide-liposome-small molecule machinery targets AML and consequently induces cell apoptosis both in vitro and in vivo through three disparate mechanisms: (I) Oridonin, as a Michael acceptor molecule, inhibits GSH function through covalent bonding, triggering an initial imbalance of oxidative stress. (II) Maleimide further induces GSH exhaustion, aggravating redox imbalance as a complementary augment with oridonin. (III) Peptide targets TLR2, enhances the directivity and enrichment of oridonin within AML cells. Conclusion The rationally designed nanocomplex provides a ROS drug enhancement and targeted delivery platform, representing a potential solution by disrupting redox balance for AML therapy.

As the negative repercussions of environmental devastation, such as air quality decline and air pollution, become more apparent, environmental consciousness is growing across the world, forcing nations to take steps to mitigate the damage. China pledged to achieve air quality improvement goal to combat global environment issue, yet the spatial-temporal differentiation and its driving factors of environment-meteorology-economic index for air quality are not fully analysed. To promote regional collaborative control of air pollution and achieve sustainable urban development, spatial and temporal different and its driving factors of air quality in Shandong Province during 2013–2020. Results revealed that concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO-95per) exhibited decreasing trend (SO2 concentrations decreasing 84 % and CO-95per concentrations decreasing 90 %). Air quality was improved from inland areas to coastal areas. Pollutant indicators of SO2, NO2, PM10, PM2.5, and CO-95per demonstrated significant positive correlation (P < 0.05). Air temperature and precipitation are significantly negatively correlated with concentrations of SO2, NO2, PM10, PM2.5, and CO-95per but significantly positively correlated with ozone (O3-8 h). SO2, NO2, PM2.5, PM10, CO-95per, and proportion of days with heavy pollution are strongly positively correlated with proportion of secondary industry but strongly negatively correlated with proportion of tertiary industry and volume of household waste. Except for O3-8 h, pollutant index of Provincial Capital Economic Circle (PCEC) and Southern Shandong Economic Circle (SSEC) has significant negative correlation (P < 0.05) with regional gross domestic product and investment in environmental protection; however, investment in environmental protection of Eastern Shandong Economic Circle (ESEC) has no significant correlation with air pollution index. There was significant negative correlation between vegetable sowing area and SSEC pollutant index. The relationship between pollution emission and investment in environmental protection has shifted from high pollution-low investment to low pollution-low investment in PCEC, ESEC and SSEC, and the inflection point was in 2020 for PCEC, 2019 for ESEC, and 2020 for SSEC. Those results provide empirical evidence and theoretical support for the improvement of regional air quality, aiming to achieve high-quality development. According to these findings, it has been found that meteorological elements, pollutant emission, socio-economic factors and agricultural data affect air quality. Those results could provide meaningful and significant supporting for synergistic regulation of diverse pollutants.

BackgroundTumor mRNA vaccines have been identified as a promising technology for cancer therapy in multiple cancer types, while their efficacy in thyroid cancer (THCA) is unclear. Immunotyping is strongly associated with the immune microenvironment and immune status in cancer, thus it is important in vaccination and therapeutic response. This study is to identify potential valuable antigens and novel immune subtypes of THCA for immune landscape construction, thus screening patients suitable for mRNA vaccination.MethodsThe clinical information and gene expression files of 568 THCA cases were obtained from the TCGA dataset. The DNA copy number variation and the somatic mutation of THCA were visualized by the cBioPortal database. TIMER was used to investigate the immune infiltrating correlation with candidate antigens. Consensus clustering analysis was conducted to cluster data using the ConsensusClusterPlus package. The immune landscapes of THCA patients were visualized using the Monocle package. The critical hub genes for THCA mRNA vaccines were identified by WGCNA package. To validate, the immunohistochemistry and real-time quantitative PCR (RT-qPCR) were performed to detect the expression level of potential antigen for mRNA vaccine in tissue and cell lines in THCA.ResultsThymidine kinase 1 (TK1) was identified as a potential biomarker of mRNA vaccine against THCA. It was confirmed to be significantly upregulated in THCA tissues and cells lines. Moreover, three novel immune subtypes of THCA were obtained based on the expression consistency of immune-associated genes. The S2 subtype was characterized as an immunological “cold” phenotype with a high expression of immunogenic cell death modulators. S1 and S3 subtypes were immunological “hot” phenotypes with immune checkpoints upregulation. Further, the immune landscape of THCA patients was visualized and ten hub genes for mRNA vaccines were identified.ConclusionTK1 was a tumor-specific antigen of mRNA vaccines. The patients belonging to the S2 subtype (“cold” tumor) were suitable for mRNA vaccine therapy in THCA. Notably, ten hub genes were conducted as potential biomarkers for identifying suitable patients for mRNA vaccination. These findings provided novel insights into mRNA vaccine development against THCA.

ObjectivesThe study aimed to translate and culturally adapt the personal suicide stigma questionnaire (PSSQ) into simplified Chinese and evaluate its psychometric properties among adolescents who have attempted suicide in mainland China.MethodsFollowing Brislin’s translation model and using purposive sampling, we surveyed 440 adolescents who had attempted suicide at Hangzhou Seventh People’s Hospital in Zhejiang Province, China. Content validity was determined by a panel of experts, and the construct validity of the scale was assessed using exploratory factor analysis (EFA), confirmatory factor analysis (CFA), convergent validity, and discriminant validity. Reliability analysis was evaluated using Cronbach’s α coefficient, test–retest reliability, and half-split reliability.ResultsThe Chinese version of the PSSQ consists of three dimensions and 14 items. After two rounds of expert consultation, the item-content validity index for all items exceeded 0.70, and the scale-content validity index exceeded 0.90. EFA extracted three factors and retained all 14 items. The CFA indicators demonstrated a good fit. The Cronbach’s α coefficient of the scale was 0.880, the half-split reliability was 0.681, and the test–retest reliability was 0.862. It is evident that the PSSQ and its subscales demonstrate stable structural validity and good internal consistency in measuring self-stigma among individuals with suicidal tendencies, indicating that the PSSQ is a reliable tool for assessing the degree of personal stigma in Chinese adolescents who have attempted suicide.ConclusionThis study ensured the linguistic and cultural appropriateness of the Chinese version of the PSSQ through cross-cultural adaptation and validation of its reliability and validity, thereby enhancing the accuracy and reliability of assessing personal stigma among Chinese adolescents who have attempted suicide. The validation of the Chinese version of the scale not only enriches the research tools available for studying personal stigma related to suicide in mainland China, but also provides a reliable quantitative tool for future research on the psychological states of individuals who have attempted suicide, the impact of stigma, and the effectiveness of interventions.

ObjectiveExplore the clinical application value of urethral mucosal pretreatment at the tip of the prostate in preventing stress urinary incontinence (SUI) after thulium laser enucleation of the prostate (ThuLEP).MethodsEighty-seven patients with benign prostatic hyperplasia (BPH) treated with ThuLEP from June 2021 to December 2022 were divided into two groups. Of these, 42 patients (group A) underwent conventional ThuLEP and 45 patients (group B) were enucleated after pretreatment of the urethral mucosa. At the tip of the prostate, pretreatment of the urethral mucosa consisted of pushing the gland separately on both sides at the level of the verumontanum and cutting off the mucosa near the external urethral sphincter clockwise and counterclockwise. The perioperative and postoperative follow-up indicators [operation time, hemoglobin reduction, complications, Qmax, International Prostate Symptom Score (IPSS), quality of life (QoL), and post-void residual (PVR) volume] of the two groups of patients were collected and compared. All patients were followed up 1 month after surgery.ResultsAll 87 procedures were successfully completed. There was no significant difference in age and gland size between the two groups (P > 0.05). There was no significant difference between operating time and hemoglobin reduction in the two groups (P > 0.05). The Qmax, IPSS, QOL, and PVR volume were significantly improved postoperatively in both groups (P 0.05).ConclusionPretreatment of the urethral mucosa before ThuLEP for BPH significantly reduces the incidence of SUI after surgery. This technique, which preconditions the apical urethral mucosa of the prostate, is safe and effective, has few complications, and is worthy of clinical application.

Abstract TnpBs encoded by the IS200/IS605 family transposon are among the most abundant prokaryotic proteins from which type V CRISPR-Cas nucleases may have evolved. Since bacterial TnpBs can be programmed for RNA-guided dsDNA cleavage in the presence of a transposon-adjacent motif (TAM), these nucleases hold immense promise for genome editing. However, the activity and targeting specificity of TnpB in homology-directed gene editing remain unknown. Here we report that a thermophilic archaeal TnpB enables efficient gene editing in the natural host. Interestingly, the TnpB has different TAM requirements for eliciting cell death and for facilitating gene editing. By systematically characterizing TAM variants, we reveal that the TnpB recognizes a broad range of TAM sequences for gene editing including those that do not elicit apparent cell death. Importantly, TnpB shows a very high targeting specificity on targets flanked by a weak TAM. Taking advantage of this feature, we successfully leverage TnpB for efficient single-nucleotide editing with templated repair. The use of different weak TAM sequences not only facilitates more flexible gene editing with increased cell survival, but also greatly expands targeting scopes, and this strategy is probably applicable to diverse CRISPR-Cas systems.

Abstract Saccharolobus islandicus REY15A represents one of the very few archaeal models with versatile genetic tools, which include efficient genome editing, gene silencing, and robust protein expression systems. However, plasmid vectors constructed for this crenarchaeon thus far are based solely on the pRN2 cryptic plasmid. Although this plasmid coexists with pRN1 in its original host, early attempts to test pRN1‐based vectors consistently failed to yield any stable host–vector system for Sa. islandicus. We hypothesized that this failure could be due to the occurrence of CRISPR immunity against pRN1 in this archaeon. We identified a putative target sequence in orf904 encoding a putative replicase on pRN1 (target N1). Mutated targets (N1a, N1b, and N1c) were then designed and tested for their capability to escape the host CRISPR immunity by using a plasmid interference assay. The results revealed that the original target triggered CRISPR immunity in this archaeon, whereas all three mutated targets did not, indicating that all the designed target mutations evaded host immunity. These mutated targets were then incorporated into orf904 individually, yielding corresponding mutated pRN1 backbones with which shuttle plasmids were constructed (pN1aSD, pN1bSD, and pN1cSD). Sa. islandicus transformation revealed that pN1aSD and pN1bSD were functional shuttle vectors, but pN1cSD lost the capability for replication. These results indicate that the missense mutations in the conserved helicase domain in pN1c inactivated the replicase. We further showed that pRN1‐based and pRN2‐based vectors were stably maintained in the archaeal cells either alone or in combination, and this yielded a dual plasmid system for genetic study with this important archaeal model.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare hematological malignancy with a highly aggressive behavior and median survival of

Objective: To observe the efficacy of haploidentcial peripheral blood stem cell transplantation combined with a single unrelated cord blood unit for severe aplastic anemia patients with donor-recipient ABO incompatibility. Methods: This was a retrospective cohort study and data of 57 severe aplastic anemia patients underwent haploidentical stem cell transplantation from August 1, 2018 to February 28, 2022 in the First Affiliated Hospital of Xi’an Jiaotong University was retrospectively analyzed. All patients were divided into two groups, the donor-recipient ABO matched group (bone marrow+peripheral blood group) using haploidentical bone marrow and peripheral blood stem cells as grafts, and donor-recipient ABO mismatched group (cord blood+peripheral blood group), using unrelated cord blood and haploidentical peripheral blood stem cells as grafts. The differences of hematopoietic reconstitution, acute and chronic graft-versus-host disease, Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection, and overall survival between the two groups were compared. Results: There were 30 cases in cord blood+peripheral blood group and 27 cases in bone marrow+peripheral blood group. One patient in bone marrow+peripheral blood group had primary graft failure, while other patients were successfully implanted. There were no significant differences of neutrophil and platelet recovery rates between two groups. The erythrocyte recovery time of cord blood+peripheral blood group was slower than that of bone marrow+peripheral blood group ( p 0.05). The incidence of grade III–IV acute graft-versus-host disease in cord blood+peripheral blood group was higher than that of bone marrow+peripheral blood group ( p 0.05). Conclusion: These findings suggest that haploidentical peripheral blood stem cell transplantation combined with a single cord blood unit may be an alternative option for severe aplastic anemia patients with donor-recipient ABO incompatibility.

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is a life-threatening and severe disease in immunocompromised hosts. A synergistic regimen based on the combination of sulfamethoxazole-trimethoprim (SMX-TMP) with caspofungin and glucocorticosteroids (GCSs) may be a potential first-line therapy for PJP. Therefore, it is important to explore the efficacy and safety of this synergistic therapy for treating non-HIV-related PJP patients. Methods We retrospectively analysed the data of 38 patients with non-HIV-related PJP at the First Affiliated Hospital of Xi’an Jiaotong University. Patients were divided into two groups: the synergistic therapy group (ST group, n = 20) and the monotherapy group (MT group, n = 18). All patients were from the ICU and were diagnosed with severe PJP. In the ST group, all patients were treated with SMX-TMP (TMP 15–20 mg/kg per day) combined with caspofungin (70 mg as the loading dose and 50 mg/day as the maintenance dose) and a GCS (methylprednisolone 40–80 mg/day). Patients in the MT group were treated only with SMX-TMP (TMP 15–20 mg/kg per day). The clinical response, adverse events and mortality were compared between the two groups. Results The percentage of patients with a positive clinical response in the ST group was significantly greater than that in the MT group (100.00% vs. 66.70%, P = 0.005). The incidence of adverse events in the MT group was greater than that in the ST group (50.00% vs. 15.00%, P = 0.022). Furthermore, the dose of TMP and duration of fever in the ST group were markedly lower than those in the MT group (15.71 mg/kg/day vs. 18.35 mg/kg/day (P = 0.001) and 7.00 days vs. 11.50 days (P = 0.029), respectively). However, there were no significant differences in all-cause mortality or duration of hospital stay between the MT group and the ST group. Conclusions Compared with SMZ/TMP monotherapy, synergistic therapy (SMZ-TMP combined with caspofungin and a GCS) for the treatment of non-HIV-related PJP can increase the clinical response rate, decrease the incidence of adverse events and shorten the duration of fever. These results indicate that synergistic therapy is effective and safe for treating severe non-HIV-related PJP.

Abstract The Multi‐Threat Medical Countermeasure (MTMC) technique is crucial for developing common biochemical signaling pathways, molecular mediators, and cellular processes. This study revealed that the Nod‐like receptor 3 (NLRP3) inflammasome pathway may be a significant contributor to the cytotoxicity induced by various organophosphorus pesticides (OPPs). The study demonstrated that exposure to six different types of OPPs (paraoxon, dichlorvos, fenthion, dipterex, dibrom, and dimethoate) led to significant cytotoxicity in BV2 cells, which was accompanied by increased expression of NLRP3 inflammasome complexes (NLRP3, ASC, Caspase‐1) and downstream inflammatory cytokines (IL‐1β, IL‐18), in which the order of cytotoxicity was dichlorvos > dipterex > dibrom > paraoxon > fenthion > dimethoate, based on the IC50 values of 274, 410, 551, 585, 2,158, and 1,527,566 μM, respectively. The findings suggest that targeting the NLRP3 inflammasome pathway could be a potential approach for developing broad‐spectrum antitoxic drugs to combat multi‐OPPs‐induced toxicity. Moreover, inhibition of NLRP3 efficiently protected the cells against cytotoxicity induced by these six OPPs, and the expression of NLRP3, ASC, Caspase‐1, IL‐1β, and IL‐18 decreased accordingly. The order of NLRP3 affinity for OPPs was dimethoate > paraoxon > dichlorvos > dibrom > (fenthion and dipterex) based on KD values of 89.8, 325, 1,460, and 2,690 μM, respectively. Furthermore, the common molecular mechanism of NLRP3‐OPPs was clarified by the presence of toxicity effector groups (benzene ring, nitrogen/oxygen‐containing functional group); =O, ‐O‐, or =S (active) groups; and combination residues (Gly271, Asp272). This finding provided valuable insights into exploring the common mechanisms of multiple threats and developing effective therapeutic strategies to prevent OPPs poisoning.

Millions of women worldwide are infertile due to gynecological disorders, including premature ovarian insufficiency, polycystic ovary syndrome, Asherman syndrome, endometrial atrophy, and fallopian tube obstruction. These conditions frequently lead to infertility and have a substantial impact on the quality of life of the affected couples, primarily because of their psychological implications and high financial costs. Recently, using platelets to stimulate cell proliferation and tissue differentiation has emerged as a promising approach in regenerative medicine. Platelet-rich plasma (PRP) shows considerable potential for promoting endometrial hypertrophy and follicle development, making it a promising therapeutic option for tissue repair or replacement. This review provides an overview of the recent advancements and underlying mechanisms of PRP therapy for various female reproductive diseases and presents new therapeutic options for addressing female infertility.

As land and sea integration continues to accelerate, it will inevitably have an effect on the marine ecological environment. However, the study on spatial and temporal distribution characteristics of Chinese marine environmental quality and its driving factors was lacking. This paper employs Regression Analysis, Spearman Correlation Analysis, Canonical Correlation Analysis, Boston Consulting Group Matrix and Environmental Kuznets Curve to examine the spatial–temporal distribution characteristics and correlation factors of Chinese jurisdictional sea areas environmental quality. The environmental quality of the waters under China's jurisdiction improved on average from 2003 to 2021, the area of sea with excellent water quality increased by 7.21 × 104 km2. The spatial distribution showed “South superior, North inferior” trend. The accumulated red tide area is 2.01 × 105 km2, and the green tide has the average maximum area of distribution is 3.13 × 104 km2. The marine dumping area's volume of waste has a three stages of slow rise (2003–2007), steady (2008–2014) and rapid rise (2015–2021). The average percentage of seawater bathing areas with good water quality is 82.10 %. Urban Environmental Infrastructure Investment and Urban Drainage Construction Investments are positively correlated with excellent water quality and negatively correlated with light-sewage water quality. The typical correlation for the group “Environmental Quality/Environmental Governance” is 0.911, and the strongest correlation is between excellent water quality and urban drainage construction investment. The typical correlation coefficient for the “Environmental Quality/Socioeconomic” group is 0.960, and the strongest correlation is between excellent water quality and per capita GDP. The Gross Ocean Product, Per Capita GDP, Proportion of Non-agricultural Industries, Year-end Resident Population, and excellent water quality are positively correlated whereas light-sewage water quality is negatively correlated. Liaoning, Tianjin, Shandong and Guangdong shift from high-pollution-low-investment to low-pollution-low-investment model. Shanghai, Zhejiang, Fujian and Hainan maintain high-pollution-low-investment model, Hainan maintains high-pollution-high-investment model. Jiangsu maintains low-pollution-low-investment model. Hebei and Guangxi shift from low-pollution-low-investment to low-pollution-high-investment model. Liaoning, Hebei, Tianjin, Shandong, Guangxi and Shanghai show inverted “N” shape, Jiangsu shows positive “N” shape, Zhejiang and Fujian show monotonic decline shape, Guangdong and Hainan show positive “U” shape. The results could provide valuable suggestions for coastal provinces to accomplish economic development and environmental improvement, which to prevent the old way of “pollution first and treatment later”.

Cytokine-like protein 1 (CYTL1) expression is deliberately downregulated during the progression of multiple types of cancers, especially breast cancer. However, the metabolic characteristics of cancer progression remain unclear. Here, we uncovered a risk of breast cancer cells harboring low CYTL1 expression, which is metabolically controlled during malignant progression. We performed metabolism comparison and revealed that breast cancer cells with low CYTL1 expression have highly suppressed transsulfuration activity that is driven by cystathionine β-synthase (CBS) and contributes to de novo cysteine synthesis. Mechanistically, CYTL1 activated Nrf2 by promoting autophagic Keap1 degradation, and Nrf2 subsequently transactivated CBS expression. Due to the lack of cellular cysteine synthesis, breast cancer cells with low CYTL1 expression showed hypersensitivity to system xc− blockade-induced ferroptosis in vitro and in vivo. Silencing CBS counteracted CYTL1-mediated ferroptosis resistance. Our results show the importance of exogeneous cysteine in breast cancer cells with low CYTL1 expression and highlight a potential metabolic vulnerability to target.

Particulate matter (PM) from residential combustion is an existential threat to human health. Emission factors (EFs) of multiple potential toxic components (PTCs) in size-resolved PM and gas from eight residential fuel combustion were measured, and size distribution, gas/particle partitioning and health risks of the PTCs were investigated. Average EFs from clean coal and anthracite coal were PTEs (sum of EFs of 11 Potential Toxic Elements, 6.62 mg/kg fuels) > PAHs (sum of 22 Polycyclic Aromatic Hydrocarbons, 1.12 mg/kg) > OPAHs (sum of 5 Oxygenated Polycyclic Aromatic Hydrocarbons, 0.45 mg/kg) > PAEs (sum of 6 Phthalate Esters, 0.11 mg/kg) > NPAHs (sum of 14 Nitropolycyclic Aromatic Hydrocarbons, 16.84 μg/kg) > OPEs (sum of 7 Organophosphate Esters, 7.57 μg/kg) > PCBs (sum of 6 Polychorinated Biphenyls, 0.07 μg/kg), which were 2–3 and 1–2 orders of magnitude lower than the EFs of PTCs (except PTEs) from bituminous coal and biomass. Most PAHs, OPAHs and NPAHs, which may mainly originate from chemical reactions, showed similar size distributions and averagely 85 % concentrated in PM1. PTEs, PAEs, OPEs and PCBs generated from the release from raw fuels may have a higher proportion, so their size distributions were more complex and varied with combustion temperature, volatility of compounds, binding mode of the raw fuels, and so on. In addition, clean coal and high-quality anthracite coal could reduce the health risks from the potential organic toxic components, but also reveal the stumbling block of PTEs in risk control.

The influence of soil salinization on nitrogen (N) transformation is largely unknown, which impedes the reasonable management of N in saline fields. A comprehensive meta-analysis was thus conducted to evaluate the effects of salinity and relative soil physicochemical properties on net N mineralization and nitrification in upland soils. Results showed that effects of salinity on the net-N mineralization rate (Min) and nitrification rate (Nit) changed with the salinity level and incubation time. Generally, the inhibitory effect of salt on Min and Nit decreased gradually with incubation time. At 14–16 days of soil incubation, significant stimulatory effects on Min were observed in middle-level (ECe: 12–16 dS m-1) and high-level (ECe >16 dS m-1) saline soils, and on Nit in low-level (ECe: 4–12 dS m-1) saline soils. Regression analysis revealed that the effects of soil organic carbon (SOC), total N (TN), C/N, pH, and clay content on Min and Nit were closely related to salinity levels. Nit at 5–7 days of soil incubation first enhanced and then decreased with C/N increase, and the threshold value was 34.7. The effect of pH on Nit changed with salinity levels, and shifted from stimulation to inhibition with increasing pH. Min at 5–7 days of soil incubation in middle-level group first increased with increasing pH, and decreased when pH was higher than 8.1. Salinization deeply affected soil properties, which further influenced N turnover via alteration of the availability of substrates and microbial biomass and activities. Our findings suggest that the influence of salinity on soil N turnover closely related with salinity level, and salinity level should be considered fully when optimizing N management in saline upland fields.

Objective Fluid extravasation is a potentially dangerous complication associated with shoulder arthroscopy. Most relevant studies have involved respiratory system, while the primary purpose was to reveal the effects of the fluid extravasation on cardiovascular system and postoperative function. Methods The clinical data of 92 patients was retrospective analyzed, in which 84 cases with rotator cuff injury, three cases with shoulder instability, three cases with fractures of the greater tuberosity of the humerus, and two cases with frozen shoulder. All the patients were undergoing shoulder arthroscopy. The relationship between the basic information of the patients and cardiac index (CI) or pulse pressure variation (PPV) were evaluated by linear regression analysis. The change of CI or PPV at different states were evaluated by the one‐way analysis of variance. The liquid retention (TR) and postoperative clinical outcomes was analyzed using linear regression. Results The preoperative CI was affected by anesthesia status and body position, while PPV was not affected. Multivariate mixed‐effects model analysis of CI found that there was a statistically significant difference in groups of older than 55 years old and those with obesity (BMI > 24). After the operation, the retention of irrigation fluid significantly influenced the circumference of the deltoid (P

Thorough and precise gene structure annotations are essential for maximizing the benefits of genomic data and unveiling valuable genetic insights. The cucumber genome was first released in 2009 and updated in 2019. To increase the accuracy of the predicted gene models, 64 published RNA-seq data and 9 new strand-specific RNA-seq data from multiple tissues were used for manual comparison with the gene models. The updated annotation file (V3.1) contains an increased number (24,145) of predicted genes compared to the previous version (24,317 genes), with a higher BUSCO value of 96.9%. A total of 6231 and 1490 transcripts were adjusted and newly added, respectively, accounting for 31.99% of the overall gene tally. These newly added and adjusted genes were renamed (CsaV3.1_XGXXXXX), while genes remaining unaltered preserved their original designations. A random selection of 21 modified/added genes were validated using RT-PCR analyses. Additionally, tissue-specific patterns of gene expression were examined using the newly obtained transcriptome data with the revised gene prediction model. This improved annotation of the cucumber genome will provide essential and accurate resources for studies in cucumber.

Abstract Designing Pt-based electrocatalysts with high catalytic activity and CO tolerance is challenging but extremely desirable for alkaline hydrogen oxidation reaction. Herein we report the design of a series of single-atom lanthanide (La, Ce, Pr, Nd, and Lu)-embedded ultrasmall Pt nanoclusters for efficient alkaline hydrogen electro-oxidation catalysis based on vapor filling and spatially confined reduction/growth of metal species. Mechanism studies reveal that oxophilic single-atom lanthanide species in Pt nanoclusters can serve as the Lewis acid site for selective OH- adsorption and regulate the binding strength of intermediates on Pt sites, which promotes the kinetics of hydrogen oxidation and CO oxidation by accelerating the combination of OH− and *H/*CO in kinetics and thermodynamics, endowing the electrocatalyst with up to 14.3-times higher mass activity than commercial Pt/C and enhanced CO tolerance. This work may shed light on the design of metal nanocluster-based electrocatalysts for energy conversion.

Abstract Different types of network traffic can be treated as data originating from different domains with the same objectives of problem-solving. Previous work utilizing multi-domain machine learning has primarily assumed that data in different domains have the same distribution, which fails to effectively address the domain offset problem and may not achieve excellent performance in every domain. To address these limitations, this study proposes an attention-based bidirectional long short-term memory (Bi-LSTM) model for detecting coordinated network attacks, such as malware detection, VPN encapsulation recognition, and Trojan horse classification. To begin, HTTP traffic is modeled as a series of natural language sequences, where each request follows strict structural standards and language logic. The Bi-LSTM model is designed within the framework of multi-domain machine learning technologies to recognize anomalies of network attacks from different domains. Experiments on real HTTP traffic data sets demonstrate that the proposed model has good performance in detecting abnormal network traffic and exhibits strong generalization ability, enabling it to effectively detect different network attacks simultaneously.

Abstract In order to solve the requirements of real-time detection on metallic gaskets of wheelset assembly under the condition of limited hardware resources, here we propose an improved lightweight YOLOX-like network that can be deployed on mobile devices with low computing resource consumption. Firstly, the basic components of ShuffleNetV2 network structure are trimmed to reduce the computation intensity and the number of training parameters. Thus the lightweight ShuffleNetV2 is used as the backbone structure of YOLOX. The prediction layer for $$20\times 20$$ 20 × 20 size large targets is also removed from the head of this structure to further reduce the calculation time and improve the inference speed. Besides, the channel-attention enhancement module efficient channel attention is added into the network to improve the capability of feature extraction and the accuracy of target detection. Finally, the verification of inference for the proposed model is carried out on mobile terminal devices.The results show that the improved lightweight algorithm proposed in this paper not only ensures the detection accuracy, but also greatly reduces training parameters and computing resources, and it particularly can be run rapidly on mobile terminal devices with low-cost of computation.

Background: The aim of this study was to evaluate the accuracy of LiveBoost™, a gradient boosting (GB)-based prediction system based on standard biochemical values (AST, ALT, platelet count) and age, in Chinese patients with chronic hepatitis B (CHB) and compare its performance with FIB-4 (fibrosis-4 score) and APRI (the aspartate transaminase to platelet ratio index). Methods: This retrospective trial enrolled 454 participants, including 279 CHB patients who underwent liver biopsy and 175 normal controls from 3 centers in China. All participants underwent laboratory blood testing. LiveBoost was constructed using GB and FIB-4 and APRI were calculated from laboratory data. Results: LiveBoost outperformed APRI and FIB-4 in predicting hepatic fibrosis and cirrhosis. The GB model had an AUROC of 0.977 for CHB diagnosis, 0.804 for early and advanced fibrosis, and 0.836 for non-cirrhosis and cirrhosis, compared to AUROC of 0.554, 0.673 and 0.720 for FIB-4, AUROC of 0.977, 0.652 and 0.654 for APRI. Conclusions: LiveBoost is a more reliable and cost-effective method than APRI and FIB-4 for assessing liver fibrosis in Chinese patients with CHB.

Objective To compare the effects of progestin-primed ovarian stimulation (PPOS) protocol and GnRH-a long protocol in infertility patients with normal ovarian reserve function undergoing invitro fertilization and embryo transfer.Methods A retrospective cohort study was conducted to analyze the clinical data of 2013 cycles of patients with normal ovarian reserve function who underwent invitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) in the Department of Human Reproductive Center, Renmin Hospital, Hubei University of Medicine from January 2018 and June 2020. The PPOS protocol group included 679 cycles and GnRH-along protocol group included 1334 cycles, the pregnancy outcomes were compared between the two groups.Results The duration of Gn used and total Gn used dosage in the PPOS protocol group were less than those in the GnRH-along protocol group (Duration of Gn used: 10.05 ± 1.48 vs 11.90 ± 1.85 d, p 0.05); In addition, no severe OHSS occurred in the PPOS protocol group during ovulation induction, while 11 patients of severe ovarian hyperstimulation syndrome (OHSS) occurred in GnRH-a long protocol group (p

ObjectiveIntermittent energy restriction (IER) is an effective weight loss strategy. However, little is known about the dynamic effects of IER on the brain-gut-microbiome axis.MethodsIn this study, a total of 25 obese individuals successfully lost weight after a 2-month IER intervention. FMRI was used to determine the activity of brain regions. Metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways in from fecal samples.ResultsOur results showed that IER longitudinally reduced the activity of obese-related brain regions at different timepoints, including the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit. IER longitudinally reduced E. coli abundance across multiple timepoints while elevating the abundance of obesity-related Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis. Correlation analysis revealed longitudinally correlations between gut bacteria abundance alterations and brain activity changes.ConclusionsThere was dynamical alteration of BGM axis (the communication of E. coli with specific brain regions) during the weight loss under the IER.

ObjectiveTo explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis.DesignA retrospective cohort study.SettingTertiary-care academic medical center.PopulationA total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020.MethodsA total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed.Main outcome measuresThe primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate.ResultsWe created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16 mm on trigger day, the estradiol (E2) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups.ConclusionThe combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.

AbstractAim To evaluate diagnostic performance of metagenomic next-generation sequencing (mNGS) for Pneumocystis jirovecii pneumonia (PCP), in comparison with polymerase chain reaction (PCR), Gomori methenamine silver (GMS) staining and serum 1,3-β-d-Glucan (BG) assay.Methods 52 PCP patients and 103 patients with non-pneumocystic jirovecii pneumonia (non-PCP) were enrolled, and comparative analysis was conducted of different diagnostic tests. Clinical features and co-pathogen characteristics were reviewed.Results The diagnostic sensitivity (92.3%) and specificity (87.4%) of mNGS did not show significant differences compared with that of PCR while mNGS had the advantage over PCR in the detection of co-pathogens. Despite its excellent specificity, the sensitivity of GMS staining (9.3%) was inferior to that of mNGS (p

Dendrobium mixture (DM) is a patented Chinese herbal medicine which has been shown to ameliorate type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro. We aimed to investigate the underlying mechanism of DM as a therapeutic agent in attenuating liver steatosis in relation to type 2 diabetes mellitus (T2DM).DM (16.2 g/kg/d) was administered to db/db mice for 4 weeks. The db/m mice and db/db mice in the control and model groups were given normal saline. Additionally, DM (11.25 g/kg/d) was administered to Sprague-Dawley (SD) rats, and the serum was collected and used in an experiment involving palmitic acid (PA)-induced human liver HepG2 cells with abnormal lipid and glucose metabolism.In db/db mice, the administration of DM significantly alleviated liver steatosis, including histological damage and cell apoptosis. DM was found to prevent the upregulation of the RAGE and AKT1 proteins in liver tissues. The underlying mechanism of DM was further studied in PA-induced HepG2 cells. Post-DM administration serum from SD rats reduced lipid accumulation and regulated glucose metabolism in HepG2 cells. Consequently, it inhibited RAGE/AKT signaling and restored autophagy activity. The upregulated autophagy was associated with the mTOR-AMPK signaling pathway. Furthermore, post-DM administration serum reduced apoptosis of hepatocytes in PA-induced HepG2 cells. Our study supports the potential use of DM as a therapeutic agent for the treatment of NAFLD in T2DM. The mechanism underlying this therapeutic potential is associated with the downregulation of the AGE/RAGE/Akt signaling pathway.

The nutritional quality of muscles and skins of different sizes: 1500.05±1.50 g, 3002.25±2.55 g and 4505.25±4.15 g, were systematically studied, which could provide basic data for processing and comprehensive utilization of hybrid sturgeon. The results showed that the muscle and skin of (3002.25±2.55) g of hybrid sturgeon accounted for the highest proportion of body weight, which were significantly higher than that of the (1500.05±1.50) g (P0.05). The results showed that the weight specifications affected the nutrient composition in muscle and skin of hybrid sturgeon, and the (3002.25±2.55) g body mass was the most balanced, suitable for deep processing and utilization.

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

In complex electromagnetic environments, satellite telemetry, tracking, and command (TT&C) signals often become submerged in background noise. Traditional TT&C signal detection algorithms suffer a significant performance degradation or can even be difficult to execute when phase information is absent. Currently, deep-learning-based detection algorithms often rely on expert-experience-driven post-processing steps, failing to achieve end-to-end signal detection. To address the aforementioned limitations of existing algorithms, we propose an intelligent satellite TT&C signal detection method based on triplet attention and Transformer (TATR). TATR introduces the residual triplet attention (ResTA) backbone network, which effectively combines spectral feature channels, frequency, and amplitude dimensions almost without introducing additional parameters. In signal detection, TATR employs a multi-head self-attention mechanism to effectively address the long-range dependency issue in spectral information. Moreover, the prediction-box-matching module based on the Hungarian algorithm eliminates the need for non-maximum suppression (NMS) post-processing steps, transforming the signal detection problem into a set prediction problem and enabling parallel output of the detection results. TATR combines the global attention capability of ResTA with the local self-attention capability of Transformer. Experimental results demonstrate that utilizing only the signal spectrum amplitude information, TATR achieves accurate detection of weak TT&C signals with signal-to-noise ratios (SNRs) of −15 dB and above (mAP@0.5 > 90%), with parameter estimation errors below 3%, which outperforms typical target detection methods.

ObjectivesWe aimed to probe the safety and effectiveness of flexible ureteroscopic lithotripsy (FURL) with a suctioning ureteral access sheath (S-UAS) for removing upper urinary calculi under local anesthesia (LA).Materials and methodsThe clinical data of 56 patients with upper urinary calculi treated by FURL with an S-UAS under LA during the period between September 2019 and November 2022 were analyzed retrospectively. For LA, intramuscular pethidine (1.0–2.0 mg/kg) and phenergan (25 mg) were administered 30 min prior to surgery, and oxybuprocaine hydrochloride gel was administered through the urethra at the start of the surgery. The S-UAS and flexible ureteroscope were used for FURL. Demographic characteristics, stone-related parameters, and clinical outcomes were analyzed.ResultA total of 66 procedures were performed successfully on 46 patients (Group A), who underwent unilateral surgeries, and on 10 patients (Group B) who underwent same-session bilateral surgeries. All 56 patients were operated upon without altering the anesthesia strategy, and none required additional analgesia. The mean stone sizes of the Group A and Group B patients were 20.24 ± 5.45 mm and 29.40 ± 3.89 mm, respectively. The mean operative times of the two groups were 53.04 ± 13.35 min and 90.00 ± 15.81 min, respectively. In Group A, the stone-free rates (SFRs) were 76.1% (35/46) and 85.1% (40/46) at postoperative day 1 and day 30, respectively. In Group B, the SFRs were 80.0% (16/20) and 85.0% (17/20), respectively. Four (8.7%) patients in Group A suffered complications such as fever, stent pain, urosepsis, and steinstrasse. In Group B, one (10%) patient suffered from fever.ConclusionFURL, combined with an S-UAS under LA, is a feasible option and provides satisfactory clinical outcomes for appropriately selected patients.

Abstract Background The incidence of hereditary spherocytosis (HS) is approximately 1:2000 in the western population, while it is much lower in the Chinese population. It is difficult to make a definite diagnosis due to the variable genotypic features and the lack of well-documented evidence for HS patients. Gene sequence examination is helpful for clear diagnosis. Case presentation: We presented the case of a 29-year-old male HS patient with skin yellowness, anorexia, and cholecystolithiasis as the first manifestations. Laboratory examination of the patient and his parents showed a mild reduction in hemoglobin and mean corpuscular hemoglobin concentration, increased reticulocytes, and promotion of indirect bilirubin in the patient and his father. Furthermore, small globular red blood cells with increased osmotic fragility were observed. In particular, the eosin-5’-maleimide binding test provided the strong evidence that band 3 protein was deleted in the erythrocyte membrane. Next-generation sequencing (NGS) and Sanger sequencing further demonstrated a heterozygous nonsense variant (exon16, c.G1985A: p.W662X) in SLC4A1, inherited from his father. Thus, the patient was diagnosed with HS, and then was effectively treated. After splenectomy, the anemia was relieved without any obvious unpleasant side effects. Conclusion We report an extremely rare case of HS in China that presented with hereditary hemolytic anemia with band 3 deletion resulting from a novel variant of SLC4A1, and systematically review a large number of related literatures. This study, therefore, significantly contributes to the literature on HS.

Abstract Background The major histocompatibility complex (MHC) and the killer cell immunoglobulin-like receptors (KIR) are key regulators of immune responses. The cynomolgus macaque, an Old World monkey species, can be applied as an important preclinical model for studying human diseases, including coronavirus disease 2019 (COVID-19). Several MHC-KIR combinations have been associated with either a poor or good prognosis. Therefore, macaques with a well-characterized immunogenetic profile may improve drug evaluation and speed up vaccine development. At present, a complete overview of the MHC and KIR haplotype organizations in cynomolgus macaques is lacking, and characterization by conventional techniques is hampered by the extensive expansion of the macaque MHC-B region that complicates the discrimination between genes and alleles. Methods We assembled complete MHC and KIR genomic regions of cynomolgus macaque using third-generation long-read sequencing approach. We identified functional Mafa-B loci at the transcriptome level using locus-specific amplification in a cohort of 33 Vietnamese cynomolgus macaques. Results This is the first physical mapping of complete MHC and KIR gene regions in a Vietnamese cynomolgus macaque. Furthermore, we identified four functional Mafa-B loci (B2, B3, B5, and B6) and showed that alleles of the Mafa-I*01, -B*056, -B*034, and -B*001 functional lineages, respectively, are highly frequent in the Vietnamese cynomolgus macaque population. Conclusion The insights into the MHC and KIR haplotype organizations and the level of diversity may refine the selection of animals with specific genetic markers for future medical research.

Objective To investigate the impact of natural killer (NK) cells in the graft on the outcome following haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). Methods We retrospectively collected data from patients who had undergone haplo-PBSCT at our centre from January 2019 to November 2021. The percentage of NK cells in stem cell grafts was detected by flow cytometry. Based on the median (range) count of NK cells (1.8 [0.4–6.0] × 10 8 /kg), patients were separated into high and low NK cell count groups. Results Data from 96 patients were analysed. Patients were evenly distributed (48 in each group) into high and low NK cell count groups. There was no significant difference in neutrophil and platelet recovery between the two groups. However, the rates of febrile neutropenia, bacterial infection, and invasive fungal disease (IFD) were significantly reduced in the high compared with the low NK cell count group. There was no significant difference in rates of cytomegalovirus (CMV) and Epstein–Barr virus (EBV) infections between groups. There was no significant difference between groups in grades II and above acute graft versus host disease (GVHD), progression-free survival (PFS), or overall survival (OS). Conclusion A high number of NK cells in the graft may reduce febrile neutropenia, IFD and bacterial infection following haplo-PBSCT but it has no significant effect on aGVHD, PFS, or OS.

ObjectiveDiagnosis classification and risk stratification are crucial in the prognosis prediction and treatment selection of acute myeloid leukemia (AML). Here, we used a database of 536 AML patients to compare the 4th and 5th WHO classifications and the 2017 and 2022 versions of ELN guidance.MethodsAML patients were classified according to the 4th and 5th WHO classifications, as well as the 2017 and 2022 versions of the European LeukemiaNet (ELN) guidance. Kaplan–Meier curves with log-rank tests were used for survival analysis.ResultsThe biggest change was that 25 (5.2%), 8 (1.6%), and 1 (0.2%) patients in the AML, not otherwise specified (NOS) group according to the 4th WHO classification, were re-classified into the AML-MR (myelodysplasia-related), KMT2A rearrangement, and NUP98 rearrangement subgroups based on the 5th WHO classification. Referring to the ELN guidance, 16 patients in the favorable group, six patients in the adverse group, and 13 patients in the intermediate group based on the 2017 ELN guidance were re-classified to the intermediate and adverse groups based on the 2022 ELN guidance. Regrettably, the Kaplan–Meier curves showed that the survival of intermediate and adverse groups could not be distinguished well according to either the 2017 or 2022 ELN guidance. To this end, we constructed a risk model for Chinese AML patients, in which the clinical information (age and gender), gene mutations (NPM1, RUNX1, SH2B3, and TP53), and fusions (CBFB::MYH11 and RUNX1::RUNX1T1) were included, and our model could help divide the patients into favorable, intermediate, and adverse groups.ConclusionThese results affirmed the clinical value of both WHO and ELN, but a more suitable prognosis model should be established in Chinese cohorts, such as the models we proposed.

The research purpose of this paper is to reveal the relationship between flood deposits, rainfall and flooding in the Loess Plateau over the last 50 years. The research in this paper is of great significance as it reveals the torrential flood events and soil erosion in the central region of the Loess Plateau. Through grading analysis and 137Cs content determination of a closed lake sedimentary profile formed by landslide-blocked rivers in middle part of Loess Plateau, Zizhou County, Shaanxi Province, the age of the sedimentary formation in the section, as well as the rainstorm events and changes of soil erosion since 1954 are studied. The results show that the sediment particle size composition in the study section is fine, mainly comprising of coarse silt, while the content of sand particles (>100 μm) is very low. The changes in137Cs content show that the sedimentary layer at a depth of 280–210 cm in the research profile was formed between 1954 and 1964, while the deep sedimentary layer at 210–70 cm was formed between 1965 and 1986 and the sedimentary layer above 70 cm depth was formed between 1987 and 2011. In total, 20 coarse particle layers (particle size >50 μm) were deposited in the lake between 1954 and 2011. The sedimentation timing of the 20 coarse particle layers was basically consistent with the timing of rainstorm events (daily rainfall ≥60 mm) in the study area, indicating that the coarse particle sediments in the lake represent rainstorm events. Soil erosion was stronger between 1954 and 1985 and was weaker after 1986.

This article reports a case of a 7-year-old child with severe pneumonia whose chest CT showed pulmonary consolidation, and bronchoscopy revealed plastic bronchitis. The metagenomic Next-Generation Sequencing (NGS) of the pulmonary lavage fluid suggested the infection of Tropheryma whipplei (T whipplei). The patient was treated with bronchial lavage to remove sputum plugs, intravenous azithromycin, and piperacillin-tazobactam and was discharged after eight days of hospitalization without any recurrence during follow-up. This article aims to raise clinical awareness of T whipplei infection and suggests that NGS for rare pathogens should be performed early for unexplained plastic bronchitis.

A novel polarity-switchable photoelectrochemical photodetector based on III-nitride/MoSxcore-shell nanowires is constructed. Such unique device architecture provides a new route for multiple-band spectrally distinctive photodetection.

Abstract Background Cisplatin resistance is one of the main causes of treatment failure and death in head and neck squamous cell carcinoma (HNSCC). A more comprehensive understanding of the cisplatin resistance mechanism and the development of effective treatment strategies are urgent. Methods RNA sequencing, RT-PCR, and immunoblotting were used to identify differentially expressed genes associated with cisplatin resistance. Gain- and loss-of-function experiments were performed to detect the effect of CREB5 on cisplatin resistance and mitochondrial apoptosis in HNSCC. Chromatin immunoprecipitation (ChIP) assay, dual-luciferase reporter assay, and immunoblotting experiments were performed to explore the underlying mechanisms of CREB5. Results CREB5 was significantly upregulated in cisplatin-resistant HNSCC (CR-HNSCC) patients, which was correlated with poor prognosis. CREB5 overexpression strikingly facilitated the cisplatin resistance of HNSCC cells in vitro and in vivo, while CREB5 knockdown enhanced cisplatin sensitivity in CR-HNSCC cells. Interestingly, the activation of AKT signaling induced by cisplatin promoted nucleus translocation of CREB5 in CR-HNSCC cells. Furthermore, CREB5 transcriptionally activated TOP1MT expression depending on the canonical motif. Moreover, CREB5 silencing could trigger mitochondrial apoptosis and overcome cisplatin resistance in CR-HNSCC cells, which could be reversed by TOP1MT overexpression. Additionally, double-targeting of CREB5 and TOP1MT could combat cisplatin resistance of HNSCC in vivo. Conclusions Our findings reveal a novel CREB5/TOP1MT axis conferring cisplatin resistance in HNSCC, which provides a new basis to develop effective strategies for overcoming cisplatin resistance.

Dendrobium mixture (DM) is a patented Chinese herbal medicine indicated which has anti-inflammatory and improved glycolipid metabolism. However, its active ingredients, targets of action, and potential mechanisms are still uncertain. Here, we investigate the role of DM as a prospective modulator of protection against non-alcoholic fatty liver disease (NAFLD) induced by type 2 diabetes mellitus (T2DM) and illustrate the molecular mechanisms potentially involved. The network pharmacology and TMT-based quantitative protomics analysis were conducted to identify potential gene targets of the active ingredients in DM against NAFLD and T2DM. DM was administered to the mice of DM group for 4 weeks, and db/m mice (control group) and db/db mice (model group) were gavaged by normal saline. DM was also given to Sprague-Dawley (SD) rats, and the serum was subjected to the palmitic acid-induced HepG2 cells with abnormal lipid metabolism. The mechanism of DM protection against T2DM-NAFLD is to improve liver function and pathological morphology by promoting peroxisome proliferator-activated receptor γ (PPARγ) activation, lowering blood glucose, improving insulin resistance (IR), and reducing inflammatory factors. In db/db mice, DM reduced RBG, body weight, and serum lipids levels, and significantly alleviated histological damage of liver steatosis and inflammation. It upregulated the PPARγ corresponding to the prediction from the bioinformatics analysis. DM significantly reduced inflammation by activating PPARγ in both db/db mice and palmitic acid-induced HepG2 cells.

Abstract Tumour cells under hypoxia tend to modulate the number and contents of extracellular vesicles (EVs) to regulate the tumour microenvironment (TME) and thus promote tumour progression. However, the mechanism of how hypoxia influences the secretion of EVs remains to be elucidated. Here, we confirm the increased production of EVs in head and neck squamous cell carcinoma (HNSCC) cells under hypoxia, where endosome‐derived EVs are the main subtype affected by insufficient O2. The accumulation of hypoxia‐inducible factor‐1α (HIF‐1α) under hypoxia directly downregulates the expression of ATP6V1A, which is pivotal to maintain the homeostasis of lysosomes. Subsequently, impaired lysosomal degradation contributes to the reduced fusion of multivesicular bodies (MVBs) with lysosomes and enables the secretion of intraluminal vesicles (ILVs) as EVs. These findings establish a HIF‐1α‐regulated lysosomal dysfunction‐EV release axis and provide an exquisite framework to better understand EV biogenesis.

Abstract Penetration of immune cells into tumor cells was believed to be immune-suppressive via cell-in-cell (CIC) mediated death of the internalized immune cells. We unexpectedly found that CIC formation largely led to the death of the host tumor cells, but not the internalized immune cells, manifesting typical features of death executed by NK cells; we named this “in-cell killing” which displays the efficacy superior to the canonical way of “kiss-killing” from outside. By profiling isogenic cells, CD44 on tumor cells was identified as a negative regulator of “in-cell killing” via inhibiting CIC formation. CD44 functions to antagonize NK cell internalization by reducing N-cadherin-mediated intercellular adhesion and by enhancing Rho GTPase-regulated cellular stiffness as well. Remarkably, antibody-mediated blockade of CD44 signaling potentiated the suppressive effects of NK cells on tumor growth associated with increased heterotypic CIC formation. Together, we identified CIC-mediated “in-cell killing” as a promising strategy for cancer immunotherapy.

Abstract Oral squamous cell carcinoma (OSCC) is the most common type of oral malignancy, and metastasis accounts for the poor prognosis of OSCC. Autophagy is considered to facilitate OSCC development by mitigating various cellular stresses; nevertheless, the mechanisms of autophagy in OSCC cell proliferation and metastasis remain unknown. In our study, high-sensitivity label-free quantitative proteomics analysis revealed nuclear protein 1 (NUPR1) as the most significantly upregulated protein in formalin-fixed paraffin-embedded tumour samples derived from OSCC patients with or without lymphatic metastasis. Moreover, NUPR1 is aberrantly expressed in the OSCC tissues and predicts low overall survival rates for OSCC patients. Notably, based on tandem mass tag-based quantitative proteomic analysis between stable NUPR1 knockdown OSCC cells and scrambled control OSCC cells, we confirmed that NUPR1 maintained autophagic flux and lysosomal functions by directly increasing transcription factor E3 (TFE3) activity, which promoted OSCC cell proliferation and metastasis in vitro and in vivo. Collectively, our data revealed that the NUPR1–TFE3 axis is a critical regulator of the autophagic machinery in OSCC progression, and this study may provide a potential therapeutic target for the treatment of OSCC.

While Pt is an active fuel cell catalyst, it’s low abundance and high cost spurs research into boosting performances from lesser Pt amounts. Here, authors design atomically precise triphenylphosphine-stabilized Pt nanoclusters with high activities and durabilities for electrocatalytic H2 oxidation.

Abstract Chlorogenic acids (CGAs) are important secondary metabolites produced in sweet potato. However, the mechanisms of their biosynthesis and regulation remain unclear. To identify potential genes involved in CGA biosynthesis, analysis of the dynamic changes in CGA components and RNA sequencing were performed on young leaves (YL), mature leaves (ML), young stems (YS), mature stems (MS) and storage roots (SR). Accordingly, we found that the accumulation of six CGA components varied among the different tissues and developmental stages, with YS and YL recording the highest levels, while SR exhibited low levels. Moreover, the transcriptome analysis yielded 59,287 unigenes, 3,767 of which were related to secondary-metabolite pathways. The differentially expressed genes (DEGs) were identified based on CGA content levels by comparing the different samples, including ML vs. YL, MS vs. YS, SR vs. YL and SR vs. YS. A total of 501 common DEGs were identified, and these were mainly implicated in the secondary metabolites biosynthesis. Additionally, eight co-expressed gene modules were identified following weighted gene co-expression network analysis, while genes in darkgrey module were highly associated with CGA accumulation. Darkgrey module analysis revealed that 12 unigenes encoding crucial enzymes (PAL, 4CL, C4H, C3H and HCT/HQT) and 42 unigenes encoding transcription factors (MYB, bHLH, WD40, WRKY, ERF, MADS, GARS, bZIP and zinc finger protein) had similar expression patterns with change trends of CGAs, suggesting their potential roles in CGA metabolism. Our findings provide new insights into the biosynthesis and regulatory mechanisms of CGA pathway, and will inform future efforts to build a genetically improve sweet potato through the breeding of high CGA content varieties.