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Powder-based fire extinguishing agents have become a kind of promising substitutes for halon extinguishing agents in civil aircrafts. However, their storage lifespan, significantly influenced by the thermal aging, emerges as a crucial yet overlooked aspect for aviation use. This study investigates the effects of thermal aging cycles on various parameters of ordinary dry powder extinguishing agent (ODPEA) and novel superhydrophobic and oleophobic ultra-fine dry powder extinguishing agent (SHOU DPEA), including surface microscopic morphology, D90 (the diameter at which 90% of the cumulative volume of particles are equal to or smaller than this value), chemical structure, hydrophobic and oleophobic angles, flowability, extinguishing time and effectiveness. The results indicate that SHOU DPEA exhibits smaller particle size, more regular particle shape, significantly superior heat stability and flowability compared to ODPEA. Furthermore, the D90 value evolution of ODPEA with aging time exhibits two stages: (a) a slow and linear growth stage (0-160 days), and (b) a rapid and substantial growth stage (160-200 days). However, SHOU DPEA shows a gradual increase in D90 value throughout the entire accelerated aging process. After 160 days of aging or more, the performance of ODPEA has significantly deteriorated, while SHOU DPEA has shown less degradation. Specially, the extinguishing concentration for the 160-day-aged ODPEA exceeds that of non-aged ODPEA by 10%, whereas the concentration of the 200-day-aged SHOU DPEA is less than 10% of the non-aged counterpart. Additionally, the predicted lifespans for ODPEA and SHOU DPEA at room temperature (25 °C) are 2715 days and over 4525 days, respectively. These findings can provide valuable guidance for assessments and the selection of aviation fire extinguishing agents., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Nowadays, chemotherapy and immunotherapy remain the major treatment strategies for Triple-Negative Breast Cancer (TNBC). Identifying biomarkers to pre-select and subclassify TNBC patients with distinct chemotherapy responses is essential. In the current study, we performed an unbiased Reverse Phase Protein Array (RPPA) on TNBC cells treated with chemotherapy compounds and found a leading significant increase of phosphor-AURKA/B/C, AURKA, AURKB, and PLK1, which fall into the mitotic kinase group. The increase of AURKA and AURKB protein was majorly due to a post-transcription level regulation, and Paclitaxel treatment induced Aurora Kinases protein phosphorylation on AURKA(T288)/AURKB(T232) sites and their protein stability. In our UAB TNBC cohort, the expression of AURKA and AURKB was significantly higher in TNBC tumors compared to normal adjacent tissues, and AURKB was found to be highly expressed in African American TNBC patients compared to European Americans. Moreover, Aurora Kinases overexpression in TNBC cells renders resistance to Paclitaxel treatment and attenuates the apoptosis effect triggered by chemotherapy treatment, suggesting Aurora Kinases could mediate the chemo-resistance in TNBC. Hence, a combination of Aurora kinase inhibitors or PROTAC degrader and taxane-type chemotherapy significantly enhanced the chemotherapy effect. In summary, we revealed that Aurora Kinases upregulation after treatment with chemotherapy could confer chemotherapy resistance to TNBC cells, and AURKB could serve as preselection markers for stratifying patients' response to neoadjuvant chemotherapy., Competing Interests: Declarations. Ethics approval and consent to participate: This project was approved by the Institutional Review Boards of the University of Alabama at Birmingham (IRB-300011620). Due to the retrospective nature of the study, Institutional Review Board waived the need of obtaining informed consent. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

In this multi-center, Phase-1 study (NCT03733717), we characterized the pharmacokinetics (PK) of the anti-CD38 antibody isatuximab (Isa) after IV administration (primary objective), and evaluated safety, immunogenicity, and preliminary anti-myeloma activity in Chinese patients with relapsed/refractory multiple myeloma (RRMM). Isa 20-mg/kg was administered weekly (QW) in cycle 1, then biweekly (Q2W). Twenty-one extensively pretreated RRMM patients (median 4 prior lines; 95.2% refractory to last regimen), received ≥ 1 dose of Isa. After first IV-infusion, mean maximum observed concentration was 402 μg/mL and mean area-under-the-concentration-versus-time curve (first 1-week dosing interval) 37,000 μg·h/mL. After repeated administration, exposure (C trough ) increased 3.11-folds (day 1/cycle 2) versus first administration (day 8/cycle 1). Safety findings were consistent with the known Isa safety profile, with no new safety signals. Any-causality, grade ≥ 3 treatment-emergent adverse events (TEAEs) were reported in 47.6% of patients. Serious, treatment-related AEs occurred in 2 patients. Isa treatment was generally well tolerated; only 1 patient discontinued due to TEAE. Preliminary efficacy results showed a 19.0% overall response rate (clinical benefit, 33.3%). Our results demonstrate a PK profile for Isa comparable to prior findings in Western and other East-Asian populations, as well as safety and tolerability of treatment with IV Isa 20-mg/kg QW-Q2W in Chinese RRMM patients.Trial registration: The trial was registered with ClinicalTrials.gov; NCT03733717. Date of first trial registration: 07/11/2018., Competing Interests: Competing interests MS, HJ, XQ, FD, and JQ: nothing to disclose. YL, ZF, SZ-L, DS, and LL are employed by Sanofi and may hold stock and/or stock options. LQ: consulting for AstraZeneca, Beigene, Xi'an Janssen, Pfizer; Speaker Bureau participation for AstraZeneca, Beigene, Xi'an Janssen, Pfizer, Roche, and Sanofi., (© 2024. The Author(s).)

The prognostic value of prostate-specific antigen (PSA) kinetics in primary high-volume metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with novel hormonal therapy agents is still unclear. Here, we retrospectively reviewed the data of 102 patients with primary high-volume mHSPC who received novel hormonal therapy agents. The median follow-up was 32.25 ± 14.51 months and the median nadir PSA (nPSA) was 0.20 (0.06, 11.71) ng/mL after treatment. The mean time to nPSA was 10.82 ± 7.27 months and 55 patients (53.9%) had a PSA-density (PSA-D) ≤ 0.08 at 3-months. Univariate and multivariate Cox regression analyses showed that the absence of visceral metastases, nPSA ≤ 0.2 and PSA-D ≤ 0.08 were independent prognostic factors for better PFS and OS (all P < 0.05). Moreover, patients with nPSA ≤ 0.2 and PSA-D ≤ 0.08 had the best PFS and OS, and the combination of the nPSA and PSA-D had a better predictive accuracy for PFS and OS than nPSA and PSA-D alone. Thus, Visceral metastases, nPSA and PSA-D were independent prognostic factors for primary high-volume mHSPC patients treated with novel hormonal therapy agents. Patients with lower nPSA and PSA-D had a best survival outcome, and the combination of nPSA and PSA-D had a better effect on prognosis predicting., (© 2024. The Author(s).)

To evaluate the dosimetric benefits and clinical feasibility of deep inspiratory breath-hold (DIBH) combined with volumetric modulated arc therapy (VMAT) in left-sided postmastectomy radiotherapy (PMRT). Eligible patients with left-sided breast cancer undergoing DIBH-based PMRT were prospectively included. Chest wall, supra/infraclavicular fossa, and/or internal mammary node irradiation (IMNI) were planned with a prescription dose of 43.5 Gy in 15 fractions. VMAT plans were designed on free breathing (FB)-and DIBH-CT to compare dosimetric parameters in heart, left anterior descending artery (LAD) and lung. Cone-beam computed tomography (CBCT) was performed before and after treatment to evaluate inter- and intra-fractional setup errors. Heart position and dose variations during treatment were estimated by fusing CBCT with DIBH-CT scans.Twenty patients were included with 10 receiving IMNI. In total, 193 pre-treatment and 39 pairs pre- and post-treatment CBCT scans were analyzed. The D mean , D max , and V 5-40 of the heart, LAD, and left lung were significantly lower in DIBH than FB (p < 0.05 for all), except for V5 of LAD (p = 0.167). The cardiopulmonary dosimetric benefits were maintained regardless of IMNI. The inter- and intra-fractional setup errors were < 0.3 cm; and the overall estimated PTV margins were < 1.0 cm. During treatment, the mean dice similarity coefficient of heart position and the mean ratio of heart D mean between CBCT and DIBH-CT plans was 0.95 (0.88-1.00) and 100% (70.6-119.5%), respectively. DIBH-VMAT could effectively reduce the cardiopulmonary doses with acceptable reproducibility and stability in left-sided PMRT regardless of IMNI., (© 2024. The Author(s).)

Heart sound auscultation plays a crucial role in the early diagnosis of cardiovascular diseases. In recent years, great achievements have been made in the automatic classification of heart sounds, but most methods are based on segmentation features and traditional classifiers and do not fully exploit existing deep networks. This paper proposes a cardiac audio classification method based on image expression of multidimensional features (CACIEMDF). First, a 102-dimensional feature vector is designed by combining the characteristics of heart sound data in the time domain, frequency domain and statistical domain. Based on the feature vector, a two-dimensional feature projection space is constructed by PCA dimensionality reduction and the convex hull algorithm, and 102 pairs of coordinate representations of the feature vector in the two-dimensional space are calculated. Each one-dimensional component of the feature vector corresponds to a pair of 2D coordinate representations. Finally, the one-dimensional feature component value and its divergence into categories are used to fill the three channels of a color image, and a Gaussian model is used to dye the image to enrich its content. The color image is sent to a deep network such as ResNet50 for classification. In this paper, three public heart sound datasets are fused, and experiments are conducted using the above methods. The results show that for the two-classification/five-classification task of heart sounds, the method in this paper can achieve a classification accuracy of 95.68%/94.53% when combined with the current deep network., (© 2024. The Author(s).)

Deep-sea trenches representing an intriguing ecosystem for exploring the survival and evolutionary strategies of microbial communities in the highly specialized deep-sea environments. Here, 29 metagenomes were obtained from sediment samples collected from Kermadec and Diamantina trenches. Notably, those samples covered a varying sampling depths (from 5321 m to 9415 m) and distinct layers within the sediment itself (from 0~40 cm in Kermadec trench and 0~24 cm in Diamantina trench). Through metagenomic binning process, we reconstructed 982 metagenome assembled genomes (MAGs) with completeness >60% and contamination <5%. Within them, completeness of 351 MAGs were >90%, while an additional 331 were >80%. Phylogenomic analysis for the MAGs revealed nearly all of them were distantly related to known cultivated isolates. The abundant bacterial MAGs affiliated to phyla of Proteobacteria, Planctomycetota, Nitrospirota, Acidobacteriota, Actinobacteriota, and Chlorofexota, while the abundant archaeal phyla affiliated with Nanoarchaeota and Thermoproteota. These results provide a dataset available for further interrogation of diversity, distribution and ecological function of deep-sea microbes existed in the trenches., (© 2024. The Author(s).)

Microbes in the sediments across a series of seamounts along the island arc of the Yap and Mariana trenches were investigated by metagenome. In this study, we reconstructed 107 metagenome-assembled genomes (MAGs), including 100 bacteria and 7 archaea. All the MAGs exhibited >75% completeness and <10% contamination, with 26 MAGs being classified as 'nearly complete' (completeness >90%), while 50 falling within 80-90% range and 31 between 75-80% complete. Phylogenomic analysis revealed that 86% (n = 92) of these MAGs represented new taxa at different taxonomical levels. The species composition of these MAGs was most consistent with the previous reports, with the most abundant phyla being Proteobacteria (n = 39), Methylomirabilota (n = 27), and Nitrospirota (n = 7). These draft genomes provided novel data on species diversity and function in the seamount microbial community, which will provide reference data for extensive comparative genomic studies across crucial phylogenetic groups worldwide., (© 2024. The Author(s).)

Cellular senescence (CS) is closely related to tumor progression. However, the studies about CS genes across human cancers have not explored the relationship between cancer senescence signature and telomere length. Additionally, single-cell analyses have not revealed the evolutionary trends of malignant cells and immune cells at the CS level. We defined a CS-associated signature, called "senescence signature", and found that patients with higher senescence signature had worse prognosis. Higher senescence signature was related to older age, higher genomic instability, longer telomeres, increased lymphocytic infiltration, higher pro-tumor immune infiltrates (Treg cells and MDSCs), and could predict responses to immune checkpoint inhibitor therapy. Single-cell analysis further reveals malignant cells and immune cells share a consistent evolutionary trend at the CS level. MAPK signaling pathway and apoptotic processes may play a key role in CS, and senescence signature may effectively predict sensitivity of MEK1/2 inhibitors, ERK1/2 inhibitors and BCL-2 family inhibitors. We also developed a new CS prediction model of cancer survival and established a portal website to apply this model ( https://bio-pub.shinyapps.io/cs&#95;nomo/ )., (© 2024. The Author(s).)

Water or mud inrush has become a common geological disaster during tunnel construction in karst areas. To study forming process and mechanism of water and mud inrushes through a filled karst conduit, water inrush and mud inrush model tests were carried out with a self-developed 3D model test system. The results show that the forming processes of water inrush and mud inrush have different forming modes. For water inrush, the forming process follows: flowing instability of filling material particles-formation of water inrush channel-water inrush occurring; while for mud inrush, the forming process follows: stability-sliding instability of the whole filling material suddenly-mud inrush occurring. Accordingly, a local instability model of critical hydraulic pressure causing water inrush and an integral sliding instability model of critical hydraulic pressure causing mud inrush were established respectively. The two analytical models reveal the mechanism of water inrush and mud inrush experiments to an extent. The calculated critical hydraulic pressures for water inrush and mud inrush are in good agreement with the test results. The distinguishment of water inrush and mud inrush through a karst conduit was discussed based on the critical hydraulic pressure and the evolution law of seepage water pressure in tests, and a criterion was given. The research results might provide guidance for the forecast of water and mud inrush disasters during the construction of tunnels in karst area., (© 2024. The Author(s).)

The content of androgen from adrenal is elevated under castration, and the mechanisms of compensatory secretion of adrenal androgen remain unknown. This study was designed to compare the transcript profiles between adrenals from noncastrated, orchiectomized and immunocastrated Yiling goats. Fifteen goats were randomly divided into three groups: pVAX-asd injection (control) group, pVAX-B2L-(G 4 S) 3 -kisspeptin-54-asd immunization (PBK-asd) group, and surgical castration (SC) group. Subsequently, serum was collected every two weeks after the initial immunization for hormone assays. At week 14 after immunization, adrenal glands were collected for transcriptome sequencing and qPCR. Serum testosterone concentration was significantly reduced in PBK-asd and SC group, demonstrating the effectiveness of castration. Both surgical and immunized castration resulted in adrenal hyperplasia, and thickness of adrenal cortex elevated. The specific genes involving castration were enriched in many pathways, including Steroid hormone biosynthesis pathway. The adrenocorticotropic hormone (ACTH), which promotes the production of adrenal steroids, and dehydroepiandrosterone (DHEA), a steroid hormone secreted by adrenal glands, both increased after castration. Further construction of co-expression network for transcription genes and traits (including adrenal weight and cortex thickness, ACTH and DHEA concentration) showed that the trait-related genes were enriched in multiple steroid-related pathways. These results showed that adrenal compensatory hyperplasia and androgen secretion caused by castration may involve in ACTH-induced steroid hormone synthesis., (© 2023. Springer Nature Limited.)

Pulmonary fibrosis (PF) is a serious progressive fibrotic disease that is characterized by excessive accumulation of extracellular matrix (ECM), thus resulting in stiff lung tissues. Lysyl oxidase (LOX) is an enzyme involved in fibrosis by catalyzing collagen cross-linking. Studies found that the ingredients in schisandra ameliorated bleomycin (BLM)-induced PF, but it is unknown whether the anti-PF of schisandra is related to LOX. In this study, we established models of PF including a mouse model stimulated by BLM and a HFL1 cell model induced by transforming growth factor (TGF)-β 1 to evaluate the inhibition effects of Schisandrin C (Sch C) on PF. We observed that Sch C treatment decreased pulmonary indexes compared to control group. Treatment of Sch C showed a significant reduction in the accumulation of ECM as evidenced by decreased expressions of α-SMA, FN, MMP2, MMP9, TIMP1 and collagen proteins such as Col 1A1, and Col 3A1. In addition, the expression of LOX in the lung tissue of mice after Sch C treatment was effectively decreased compared with the MOD group. The inhibition effects in vitro were consistent with those in vivo. Mechanistic studies revealed that Sch C significantly inhibited TGF-β 1 /Smad2/3 and TNF-α/JNK signaling pathways. In conclusion, our data demonstrated that Sch C significantly ameliorated PF in vivo and vitro, which may play an important role by reducing ECM deposition and inhibiting the production of LOX., (© 2023. Springer Nature Limited.)

The neutron capture cross section of [Formula: see text]Ta is relevant to s-process of nuclear astrophysics, extraterrestrial samples analysis in planetary geology and new generation nuclear energy system design. The [Formula: see text]Ta([Formula: see text]) cross section had been measured between 1 eV and 800 keV at the back-streaming white neutron facility (Back-n) of China spallation neutron source(CSNS) using the time-of-flight (TOF) technique and [Formula: see text] liquid scintillator detectors. The experimental results are compared with the data of several evaluated libraries and previous experiments in the resolved and unresolved resonance region. Resonance parameters are extracted using the R-Matrix code SAMMY in the 1-700 eV region. The astrophysical Maxwell average cross section(MACS) from kT = 5 to 100 keV is calculated over a sufficiently wide range of neutron energies. For the characteristic thermal energy of an astrophysical site, at kT = 30keV the MACS value of [Formula: see text]Ta is 834 ± 75 mb, which shows an obvious discrepancy with the Karlsruhe Astrophysical Database of Nucleosynthesis in Stars (KADoNiS) recommended value 766 ± 15 mb. The new measurements strongly constrain the MACS of [Formula: see text]Ta([Formula: see text]) reaction in the stellar s-process temperatures., (© 2023. Springer Nature Limited.)

Methyl-CpG-binding protein 2(MeCP2) is an important epigenetic regulatory factor that promotes many tumor developments, such as liver cancer, breast cancer, and colorectal cancer. So far, no pan-cancer analysis has been reported. Therefore, this study aims to explore pan-cancer's prognostic value, immune infiltration pattern, and biological function. We used bioinformatics methods to analyze the expression and prognostic significance of MeCP2, and the relationship between MeCP2 and clinicopathological parameters, genetic variation, methylation, phosphorylation, immune cell infiltration, and biological function in pan-cancer from using a public database. The results showed that expression of MeCP2 was up-regulated in 8 cancers and down-regulated in 2 cancers, which was remarkably correlated with the prognosis, pathological stage, grade and subtype of cancers. The promoter methylation level of MeCP2 DNA was decreased in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), liver hepatocellular carcinoma (LIHC), prostate adenocarcinoma (PRAD), uterine corpus endometrial carcinoma (UCEC), testicular germ cell tumors (TGCT), and stomach adenocarcinoma (STAD);decreased phosphorylation of S25, S90, S92, S241, S286, S325 and S435 was found in MeCP2, such as UCEC, lung adenocarcinoma (LUAD), ovarian serous cystadenocarcinoma (OV), colon adenocarcinoma (COAD), and kidney renal clear cell carcinoma (KIRC). Furthermore, MeCP2 expression was significantly associated with multiple immunomodulators and immune cell infiltration levels across most tumors. Therefore, our pan-cancer explored the prognostic markers and immunotherapeutic value of MeCP2 in different cancers., (© 2022. The Author(s).)

Megakaryocytes (MK) are mainly derived from bone marrow and are mainly involved in platelet production. Studies have shown that MK derived from bone marrow may have immune function, and that MK from peripheral blood are associated with prostate cancer. Single-cell transcriptome sequencing can help us better understand the heterogeneity and potential function of MK cell populations in bone marrow (BM), peripheral Blood (PB), and cord blood (CB) of healthy and diseased people.We integrated more than 1.2 million single-cell transcriptome data from 132 samples of PB, BM, and CB from healthy individuals and patients from different dataset. We examined the MK (including MK and product of MK) by single-cell RNA sequencing data analysis methods and identification of MK-related protein expression by the Human Protein atlas. We investigate the relationship between the MK subtype and Non-Small Cell Lung Cancer (NSCLC) in 77 non-cancer and 402 NSCLC. We found that MK were widely distributed and the amount of MK in peripheral blood was more than that in bone marrow and there were specificity MK subtypes in peripheral blood. We found classical MK1 with typical MK characteristics and non-classical MK2 closely related to immunity which was the most common subtype in bone marrow and cord blood. Classical MK1 was closely related to Non-Small Cell Lung Cancer (NSCLC) and can be used as a diagnostic marker. MK2 may have potential adaptive immune function and play a role in tumor NSCLC and autoimmune diseases Systemic Lupus Erythematosus. MK have 14 subtypes and are widely distributed in PB, CB, and BM. MK subtypes are closely related to immunity and have potential to be a diagnostic indicator of NSCLC., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Readmission due to chronic obstructive pulmonary disease (COPD) exacerbation contributes significantly to disease burden. Trend in readmission rate among COPD patients in China is not well characterized. We described the secular trend and identify risk factors of COPD-related 30-day readmission in Beijing during 2012-2017. In this retrospective cohort study, we used data from a citywide hospital discharge database in Beijing. We included patients ≥ 40 years with a primary diagnosis of COPD from 2012 to 2017. A total of 131 591 index admissions were identified. COPD-related 30-day readmission was defined as the initial admission with a primary diagnosis of COPD that occurs within 30 days from the discharge date of an index admission. Overall and annual 30-day readmission rates were calculated in the total population and subgroups defined by patient characteristics. We used multivariable logistic models to investigate risk factors for readmission and in-hospital mortality within 30 days. The overall 30-day COPD-related readmission rate was 15.8% (n = 20 808). The readmission rate increased from 11.5% in 2012 to 17.2% in 2017, with a multivariable-adjusted OR (95% CI) for annual change to be 1.08 (1.06-1.09) (P trend < 0.001). The upward trend in readmission rate levelled off at about 17% since 2014. The readmission rate of men was higher and increased faster than women. Comorbid osteoporosis, coronary heart disease, congestive heart failure, and cancer were associated with an increased risk of 30-day COPD-related readmission. The 30-day COPD-related readmission rate in Beijing showed an overall increasing trend from 2012 to 2017. Future efforts should be made to further improve care quality and reduce early readmissions of COPD patients., (© 2022. The Author(s).)

Abdominal aortic aneurysm (AAA) is a permanent expansion of the abdominal aorta that has a high mortality but limited treatment options. Phosphodiesterase (PDE) 4 family members are cAMP-specific hydrolyzing enzymes and have four isoforms (PDE4A-PDE4D). Several pan-PDE4 inhibitors are used clinically. However, the regulation and function of PDE4 in AAA remain largely unknown. Herein, we showed that PDE4D expression is upregulated in human and angiotensin II-induced mouse AAA tissues using RT-PCR, western blotting, and immunohistochemical staining. Furthermore, smooth muscle cell (SMC)-specific Pde4d knockout mice showed significantly reduced vascular destabilization and AAA development in an experimental AAA model. The PDE4 inhibitor rolipram also suppressed vascular pathogenesis and AAA formation in mice. In addition, PDE4D deficiency inhibited caspase 3 cleavage and SMC apoptosis in vivo and in vitro, as shown by bulk RNA-seq, western blotting, flow cytometry and TUNEL staining. Mechanistic studies revealed that PDE4D promotes apoptosis by suppressing the activation of cAMP-activated protein kinase A (PKA) instead of the exchange protein directly activated by cAMP (Epac). Additionally, the phosphorylation of BCL2-antagonist of cell death (Bad) was reversed by PDE4D siRNA in vitro, which indicates that PDE4D regulates SMC apoptosis via the cAMP-PKA-pBad axis. Overall, these findings indicate that PDE4D upregulation in SMCs plays a causative role in AAA development and suggest that pharmacological inhibition of PDE4 may represent a potential therapeutic strategy., (© 2022. The Author(s).)

Cryptosporidium spp. and Giardia duodenalis are commonly detected intestinal protozoa species in humans and animals, contributing to global gastroenteritis spread. The present study examined the prevalence and zoonotic potential of Cryptosporidium spp. and G. duodenalis in Himalayan marmots and Alashan ground squirrels in China's Qinghai-Tibetan Plateau area (QTPA) for the first time. Four hundred ninety-eight intestinal content samples were collected from five counties of QTPA of Gansu province, China. All samples were examined for Cryptosporidium spp. and G. duodenalis by PCR amplification. The resultant data were statistically analyzed by chi-square, Fisher's test and Bonferroni correction using SPSS software 25. 0. Cryptosporidium positive samples were further subtyped through analysis of the 60-kDa glycoprotein (gp60) gene sequence. A total of 11 and 8 samples were positive for Cryptosporidium spp. and G. duodenalis, respectively. Prevalence of Cryptosporidium spp. and G. duodenalis were 2.5% (10/399) and 1.5% (6/399) in Himalayan marmots, 1.0% (1/99) and 2.0% (2/99) in Alashan ground squirrels, respectively. Sequence analysis confirmed the presence of C. rubeyi (n = 2), ground squirrel genotype II (n = 7), chipmunk genotype V (n = 1) and horse genotype (n = 1). The horse genotype was further subtyped as novel subtype VIbA10. G. duodenalis zoonotic assemblages A (n = 1), B (n = 6), E (n = 1) were identified in the present study. This is the first study to identify Cryptosporidium spp. and G. duodenalis in Himalayan marmots and Alashan ground squirrels, suggesting the potential zoonotic transmission of the two pathogens in QTPA., (© 2022. The Author(s).)

Low phosphorus use efficiency (PUE) is one of the main problems of acidic soil that limit the crop growth. Therefore, in the present study, we investigated the response of crop yield and PUE to the long-term application of fertilizers and quicklime (CaO) in the acidic soil under wheat-maize rotation system. Treatments included, CK (no fertilization), NP (inorganic nitrogen and P fertilization), NPK (inorganic N, P and potassium fertilization), NPKS (NPK + straw return), NPCa (NP + lime), NPKCa (NPK + lime) and NPKSCa (NPKS + lime). Results showed that, fertilizer without lime treatments, significantly (p ≤ 0.05) decreased soil pH and crop yield, compared to the fertilizer with lime treatments during the period of 2012-2018. Average among years, compared to the CK treatment, wheat grain yield increased by 138%, 213%, 198%, 547%, 688% and 626%, respectively and maize yield increased by 687%, 1887%, 1651%, 2605%, 5047% and 5077%, respectively, under the NP, NPK, NPKS, NPCa, NPKCa and NPKSCa treatments. Lime application significantly increased soil exchangeable base cations (Ca 2+ and Mg 2+ ) and decreased Al 3+ cation. Compared to the NP treatment, phosphorus use efficiency (PUE) increased by 220%, 212%, 409%, 807% and 795%, respectively, under the NPK, NPKS, NPCa, NPKCa and NPKSCa treatments. Soil pH showed significant negative relationship with exchangeable Al 3+ and soil total N. While, soil pH showed significant (p ≤ 0.05) positive relationship with exchangeable Ca 2+ , PUE and annual crop yield. PUE was highly negatively correlated with soil exchangeable Al 3+ . In addition, soil exchangeable Ca 2+ , pH, exchangeable Al 3+ and available N were the most influencing factors of crop yield. Therefore, we concluded that lime application is an effective strategy to mitigate soil acidification and to increase PUE through increasing exchangeable base cations and reducing the acidic cations for high crop yield in acidic soil.

Brain tumors are dynamic complex ecosystems with multiple cell types. To model the brain tumor microenvironment in a reproducible and scalable system, we developed a rapid three-dimensional (3D) bioprinting method to construct clinically relevant biomimetic tissue models. In recurrent glioblastoma, macrophages/microglia prominently contribute to the tumor mass. To parse the function of macrophages in 3D, we compared the growth of glioblastoma stem cells (GSCs) alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel, with or without macrophage. Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival, maintenance of stemness, invasion, and drug resistance. Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs, relative to sphere culture. Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity, cellular crosstalk, invasion, context-specific functional dependencies, as well as immunologic interactions in a species-matched neural environment.

Plasma cell myeloma (PCM) secretes monoclonal immunoglobulin (Ig) by clonal plasma cells of abnormal proliferation in the bone marrow. As PCM is incurable, it is necessary to find new biomarkers to predict the prognosis and recurrence of PCM. The relationship between cancer and RBBP8 has not been fully studied. The role of RBBP8 in tumorigenesis remains inconsistent. We described the expression of RBBP8 in the gene expression profile of 1930 PCM samples (1878 PCM patients) from seven independent data sets. We analyzed the relationship between RBBP8 and survival prognosis, recurrence, and treatment response in patients with PCM, and the biological significance of RBBP8 in PCM. The gene expression level of RBBP8 was significantly related to the International staging system (ISS) grade of PCM (P = 0.0012). RBBP8 expression in different molecular subtypes was different (P < 2.2e-16). High RBBP8 expression is associated with poor survival in PCM (P < 0.0001). High expression of RBBP8 indicates that PCM patients are more likely to relapse (P = 0.0078). The biological significance of RBBP8 in PCM is related to the cell cycle (P < 0.05). High RBBP8 expression predicts poorer survival and more likely relapse in PCM. RBBP8 plays an important role in the cell cycle of PCM. RBBP8 can be considered an independent prognostic factor for PCM. RBBP8 can be used as a potential biomarker for assessing the prognosis of PCM patients.

Acute myeloid leukemia (AML) is a malignant hematological disease in which nearly half have normal cytogenetics. We have tried to find some significant molecular markers for this part of the cytogenetic normal AML, which hopes to provide a benefit for the diagnosis, molecular typing and prognosis prediction of AML patients. In the present study, we calculated and compared the gene expression profiles of cytogenetically normal acute myeloid leukemia (CN-AML) patients in database of The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and dataset Vizome (a total of 632 CN-AML samples), and we have demonstrated a correlation between PDE7B gene and CN-AML. Then we proceeded to a survival analysis and prognostic risk analysis between the expression levels of PDE7B gene and CN-AML patients. The result showed that the event-free survival (EFS) and overall survival (OS) were significantly shorter in CN-AML patients with high PDE7B levels in each dataset. And we detected a significantly higher expression level of PDE7B in the leukemia stem cell (LSC) positive group. The Cox proportional hazards regression model showed that PDE7B is an independent risk predictor for CN-AML. All results indicate that PDE7B is an unfavorable prognostic factor for CN-AML.

Multiple myeloma (MM) is one of hematological malignancies, characterized by malignant proliferation of plasma cells. Biomarkers play an important role in evaluating the development and prognosis of MM. Ubiquitin-conjugating enzyme E2T (UBE2T) is served to connect with particular E3 ubiquitin ligase to degraded-related substrates, contributing to DNA repair in the Fanconi anemia pathway. Also, numerous evidences reported that UBE2T is closely related to cell proliferation and carcinogenesis. However, the relationship between MM and UBE2T has not been studied. Here, we integrated eight datasets and analyzed the relationship of expression of UBE2T and ISS, 1q21, relapse and survival in MM 2684 patients (totally 2893 samples). We found that the expression of UBE2T increased with the deterioration of MM (P = 1.4e-07), especially in the early stage. UBE2T is closely related to IgG serotype MM (P = 6.9e-05). High expression of UBE2T is associated with poor survival and prognosis (EFS: P = 1.43e-03, OS: P = 5.47e-05). UBE2T is likely to play a part in the cell division pathway, affecting the survival and prognosis of MM. Therefore, UBE2T could be considered as an early alternative biomarker for the prognosis of MM.

Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) have a poor prognosis. Chimeric antigen receptor (CAR) modified T cells targeting CD19 hold great promise to improve the complete response rates of DLBCL patients compared with conventional therapies. Here, we conducted a clinical trial to evaluate the efficacy and safety of CAR-T cells. Five patients with relapsed or refractory DLBCL were treated with autologous T cells expressing the 19-41BBz chimeric antigen receptor (CAR) specifically targeted the CD19 antigen (IM19 CAR-T). The development of cytokine release syndrome (CRS) was observed. And the efficacy of IM19 CAR-T cell treatment was measured with positron emission tomography (PET)-computed tomography (CT). Of the four patients evaluable for response, two obtained complete responses (CRs), one obtained partial response (PR), and one had stable disease (SD). Remarkably, among the five patients, only one developed grade 2 CRS while the others only elicited grade 1 CRS. Additionally, the efficacy and safety of IM19 CAR-T cells were correlated with the peak blood level and persistence of CAR-T cells, as well as the immunophenotype of T-cell subsets. Overall, this study indicates the feasibility and effectiveness of IM19 CAR-T cells in the treatment of refractory or relapsed diffuse large B-cell lymphoma.

Mangrove forests are widespread along the subtropical and tropical coasts. They provide a habitat for a wide variety of plants, animals and microorganisms, and act as a buffer zone between the ocean and land. Along with other coastal environments, mangrove ecosystems are under increasing pressure from human activities, such as excessive input of nutrients and toxic pollutants. Despite efforts to understand the diversity of microbes in mangrove sediments, their metabolic capability in pristine and contaminated mangrove sediments remains largely unknown. By using metagenomic approach, we investigated the metabolic capacity of microorganisms in contaminated (CMS) and pristine (PMS) mangrove sediments at subtropical and tropical coastal sites. When comparing the CMS with PMS, we found that the former had a reduced diazotroph abundance and nitrogen fixing capability, but an enhanced metabolism that is related to the generation of microbial greenhouse gases via increased methanogenesis and sulfate reduction. In addition, a high concentration of heavy metals (mainly Zn, Cd, and Pb) and abundance of metal/antibiotic resistance encoding genes were found in CMS. Together, these data provide evidence that contamination in mangrove sediment can markedly change microbial community and metabolism; however, no significant differences in gene distribution were found between the subtropical and tropical mangrove sediments. In summary, contamination in mangrove sediments might weaken the microbial metabolisms that enable the mangrove ecosystems to act as a buffer zone for terrestrial nutrients deposition, and induce bioremediation processes accompanied with an increase in greenhouse gas emission.

Picoeukaryotes play prominent roles in the biogeochemical cycles in marine ecosystems. However, their molecular diversity studies have been confined in marine surface waters or shallow coastal sediments. Here, we investigated the diversity and metabolic activity of picoeukaryotic communities at depths ranging from the surface to the abyssopelagic zone in the western Pacific Ocean above the north and south slopes of the Mariana Trench. This was achieved by amplifying and sequencing the V4 region of both 18S ribosomal DNA and cDNA using Illumina HiSeq sequencing. Our study revealed: (1) Four super-groups (i.e., Alveolata, Opisthokonta, Rhizaria and Stramenopiles) dominated the picoeukaryote assemblages through the water column, although they accounted for different proportions at DNA and cDNA levels. Our data expand the deep-sea assemblages from current bathypelagic to abyssopelagic zones. (2) Using the cDNA-DNA ratio as a proxy of relative metabolic activity, the highest activity for most subgroups was usually found in the mesopelagic zone; and (3) Population shift along the vertical scale was more prominent than that on the horizontal differences, which might be explained by the sharp physicochemical gradients along the water depths. Overall, our study provides a better understanding of the diversity and metabolic activity of picoeukaryotes in water columns of the deep ocean in response to varying environmental conditions.

We derive full-vectorial nonlinear propagation equations of dual-pumped four-wave mixing in straight waveguides, which are valid in characterizing the one-to-six wavelength multicasting. Special attention is paid to the resulting idler wavelengths and their conversion efficiency, which enables the optimization of the experimental designs, including the incident wavelength and the power of pumps and signal. We validate the model by comparing the numerical simulation to the experimental measurement in a silicon-on-insulator waveguide, for the first time to our best knowledge, and achieve a good agreement. We further derive the general form of the proposed model for the case of using multiple,pumps, which holds a potential to numerically predict the performance of complex wavelength multicasting, and essentially guide the waveguide designs.

Programmed cell death-1 (PD-1) belongs to an inhibitory signaling pathway capable of maintaining central and peripheral immune tolerance. Blockage of PD-1 has been identified as a promising immunotherapeutic approach for cancer and chronic infectious diseases. However, it is unknown whether PD-1 pathway regulates stem cell function. It is generally believed that mesenchymal stem cells (MSCs) produce PD-1 ligand, but fail to express PD-1. In this study, we show that neural crest-derived MSCs from dental pulp (MSC-DP), but not MSCs from bone marrow, expressed PD-1. Knocking down PD-1 expression in MSC-DP results in a significantly reduced capacity for cell proliferation and accelerated multipotential differentiation. Mechanistically, we show that PD-1 regulates a SHP2/ERK/Notch cascade to maintain proliferation and a SHP2/ERK/β-catenin cascade to inhibit osteo-/odontogenic differentiation. This study indicates that PD-1 is a key surface molecule controlling cell proliferation and multipotential differentiation of MSC-DP. Through regulating PD-1/SHP2/ERK signaling, we can significantly improve the quality and quantity of culture-expanded MSC-DP for potential clinical therapies.

Creating optical components that allow light to propagate in only one direction-that is, that allow non-reciprocal propagation or 'isolation' of light-is important for a range of applications. Non-reciprocal propagation of sound can be achieved simply by using mechanical components that spin 1,2 . Spinning also affects de Broglie waves 3 , so a similar idea could be applied in optics. However, the extreme rotation rates that would be required, owing to light travelling much faster than sound, lead to unwanted wobbling. This wobbling makes it difficult to maintain the separation between the spinning devices and the couplers to within tolerance ranges of several nanometres, which is essential for critical coupling 4,5 . Consequently, previous applications of optical 6-17 and optomechanical 10,17-20 isolation have used alternative methods. In hard-drive technology, the magnetic read heads of a hard-disk drive fly aerodynamically above the rapidly rotating disk with nanometre precision, separated by a thin film of air with near-zero drag that acts as a lubrication layer 21 . Inspired by this, here we report the fabrication of photonic couplers (tapered fibres that couple light into the resonators) that similarly fly above spherical resonators with a separation of only a few nanometres. The resonators spin fast enough to split their counter-circulating optical modes, making the fibre coupler transparent from one side while simultaneously opaque from the other-that is, generating irreversible transmission. Our setup provides 99.6 per cent isolation of light in standard telecommunication fibres, of the type used for fibre-based quantum interconnects 22 . Unlike flat geometries, such as between a magnetic head and spinning disk, the saddle-like, convex geometry of the fibre and sphere in our setup makes it relatively easy to bring the two closer together, which could enable surface-science studies at nanometre-scale separations.

To gain insight into the molecular pathogenesis of patients with mantle cell lymphoma (MCL), next-generation whole-exome sequencing of 16 MCL patients was performed. We identified recurrent mutations in genes that are well known to be functionally relevant in MCL, including ATM (37.5%), TP53 (31.3%), WHSC1 (31.3%), CCND1 (18.8%), NOTCH2 (6.3%), and CDKN2A (6.3%). We also identified somatic mutations in genes for which a functional role in MCL has not been previously suspected. These genes included CCDC15, APC, CDH1, S1PR1, ATRX, BRCA2, CASP8, and NOTCH3. Further, we investigated the prognostic factors associated with MCL from clinical, pathological, and genetic mutations. Mutations of TP53 (P = 0.021) was a significant prognostic factor with shorter overall survival (OS). Although there was no statistical difference, the median survival time of patients with WHSC1 mutations was shorter than those without mutations (P = 0.070). Mutations in ATM and CCND1 had no prognostic value (P = 0.552, 0.566). When adjusted for MCL International Prognostic Index (MIPI) or combined MCL-International Prognostic Index (MIPI-c), TP53 and WHSC1 mutations were the most important prognostic factors in MCL (P < 0.05). Our data provide an unbiased view of the landscape of mutations in MCL and commend that all patients benefit from mutations of TP53 and WHSC1 at diagnosis, in addition to MIPI and MIPI-c score.

Recent years have witnessed a surge of research in two-dimensional (2D) nanostructures for development of new rechargeable Li/Na-ion battery systems. Herein, via first-principles calculations we demonstrate strain-engineered Li/Na adsorption and storage in 2D MoS 2 as anode material, aiming to enhance the operating performance of Li/Na-ion batteries. Our results show that tensile strain greatly increases the adsorption of Li/Na atoms on MoS 2 , and a modest strain of 6% increases Li (Na) adsorption energy by over 70%, which originates from the strain-induced upshift of Mo d states towards Fermi level that interact strongly with Li/Na s states, in analogy with the d-band model in metal catalyst. Significant narrowing of the n-doped semiconducting gap of MoS 2 suggests the improved electric conductivity that may benefit charge carrier transport. By mapping out the potential energy surfaces, we show shallow energy barriers of ion diffusion with ~0.2 eV for Li and 0.1 eV for Na. Furthermore, the strain-steered competition between chemical bonding and coulomb repulsion results in high Li/Na storage capability and relatively low average operating voltage. We believe that the fundamental principle underlying the use of strain to enhance performance of renewable ion battery is applicable to other stretchable low-dimensional nanomaterials.

Mammal embryos can be impaired by mother's excessive ethanol uptake, which induces a higher level of reactive oxygen species (ROS) and interferes in one carbon unit metabolism. Here, our analysis by in vitro culture system reveals immediate effect of ethanol in medium on mouse embryo development presents concentration dependent. A preimplantation embryo culture using medium contained 1% ethanol could impact greatly early embryos development, and harmful effect of ethanol on preimplantation embryos would last during the whole development period including of reducing ratio of blastocyst formation and implantation, and deteriorating postimplantation development. Supplement of 50 μg/ml betaine into culture medium can effectively reduce the level of ROS caused by ethanol in embryo cells and rescue embryo development at each stage damaged by ethanol, but supplement of glycine can't rescue embryo development as does betaine. Results of 5-methylcytosine immunodetection indicate that supplement of betaine into medium can reduce the rising global level of genome DNA methylation in blastocyst cells caused by 1% ethanol, but glycine can't play the same impact. The current findings demonstrate that betaine can effectively rescue development of embryos harmed by ethanol, and possibly by restoring global level of genome DNA methylation in blastocysts.

To investigate the usefulness of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in discriminating the pathological complete response (pCR) to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC), 42 patients underwent preoperative IVIM-DWI before (pre-nCRT) and after nCRT (post-nCRT). The values of pre-nCRT and post-nCRT IVIM-DWI parameters (ADC, D, D* and f), together with the percentage changes (∆% parametric value) induced by nCRT, were compared between the pCR (tumour regression grade [TRG] 4) and non-pCR (TRG 0, 1, 2 or 3) groups and between the GR (TRG 3 or 4) and PR (TRG 0, 1 or 2) groups based on the Dworak TRG system. After nCRT, the ADC and D values for LARC increased significantly (all P < 0.05). The TRG score revealed a positive correlation with pref (r = 0.357, P = 0.020), postD (r = 0.551, P < 0.001) and Δ%D (r = 0.605, P < 0.001). The pCR group (n = 10) had higher preD*, pref, postD, ∆%ADC and ∆%D values than the non-pCR group (n = 32) (all P < 0.05). The GR group (n = 15) exhibited higher postD, ∆%ADC and ∆%D values than the PR group (n = 27) (all P < 0.05). Based on ROC analysis, ∆%D had a higher area under the curve value than ∆%ADC (P = 0.009) in discriminating the pCR from non-pCR groups. In conclusion, IVIM-DWI may be helpful in identifying the pCR to nCRT for LARC and is more accurate than traditional DWI.

Pseudomonas aeruginosa is a formidable pathogen that is responsible for a diverse spectrum of human infectious diseases, resulting in considerable annual mortality rates. Because of biofilm formation and its ability of rapidly acquires of resistance to many antibiotics, P. aeruginosa related infections are difficult to treat, and therefore, developing an effective vaccine is the most promising method for combating infection. In the present study, we designed a novel trivalent vaccine, PcrV 28-294 -OprI 25-83 -Hcp1 1-162 (POH), and evaluated its protective efficacy in murine pneumonia and burn models. POH existed as a dimer in solution, it induced better protection efficacy in P. aeruginosa lethal pneumonia and murine burn models than single components alone when formulated with Al(OH) 3 adjuvant, and it showed broad immune protection against several clinical isolates of P. aeruginosa. Immunization with POH induced strong immune responses and resulted in reduced bacterial loads, decreased pathology, inflammatory cytokine expression and inflammatory cell infiltration. Furthermore, in vitro opsonophagocytic killing assay and passive immunization studies indicated that the protective efficacy mediated by POH vaccination was largely attributed to POH-specific antibodies. Taken together, these data provided evidence that POH is a potentially promising vaccine candidate for combating P. aeruginosa infection in pneumonia and burn infections.

We study mechanical cooling in systems of coupled passive (lossy) and active (with gain) optical resonators. We find that for a driving laser which is red-detuned with respect to the cavity frequency, the supermode structure of the system is radically changed, featuring the emergence of genuine high-order exceptional points. This in turn leads to giant enhancement of both the mechanical damping and the spring stiffness, facilitating low-power mechanical cooling in the vicinity of gain-loss balance. This opens up new avenues of steering micromechanical devices with exceptional points beyond the lowest-order two.

The present work investigated the protective effects on liver, kidneys and pancreas of spent mushroom compost polysaccharide (SCP) and its hydrolysates (enzymatic- (ESCP) and acid-hydrolyzed SCP (ASCP)) from Hypsizigus marmoreus, in streptozotocin (STZ)-induced diabetic mice. The results showed that enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) and non-enzymatic activities (total antioxidant capacity (T-AOC)) were significantly increased, the lipid peroxide contents (lipid peroxide (LPO) and malonaldehyde (MDA)) were remarkably reduced, and the clinical parameters were observably mitigated in diabetic mice treated with these three polysaccharides. Furthermore, histological observations also indicated recovery. These conclusions demonstrated that both SCP and its hydrolysates ESCP and ASCP possessed potent antioxidant activities and can be used as a potentially functional food for the prevention of diabetes and its complications induced by STZ.

Microtubule-associated protein 7 (MAP7) plays an important role in cancer cells. In this study, we identified the prognostic significance of MAP7 expression in cytogenetically normal acute myeloid leukemia (CN-AML) patients (aged <60 years) based on several microarray datasets. In the first group (n = 129), high MAP7 expression (MAP7 high ) was associated with adverse overall survival (OS; P = 0.0441) and event-free survival (EFS; P = 0.0114) compared with low MAP7 expression (MAP7 low ). In addition, the prognostic significance of MAP7 was confirmed by European Leukemia Net (ELN) intermediate-I genetic categories and multivariable analysis. In the second independent group of CN-AML patients (aged <60 years), MAP7 high was also associated with adverse OS (n = 88, OS; P = 0.00811). To understand the inherent mechanisms of MAP7's prognosis, we investigated genome-wide gene/microRNA expression signatures associated with MAP7 expression. Several known oncogenic genes/microRNAs and anti-oncogenic genes/microRNAs were disordered in MAP7 high CN-AML patients. In conclusion, MAP7 high is an adverse prognostic biomarker for CN-AML, which may be attributed to the distinctive genome-wide gene/microRNA expression and related cell signaling pathways.

The Casimir force, originating from vacuum zero-point energy, is one of the most intriguing purely quantum effects. It has attracted renewed interests in current field of nanomechanics, due to the rapid size decrease of on-chip devices. Here we study the optomechanically-induced transparency (OMIT) with a tunable Casimir force. We find that the optical output rate can be significantly altered by the vacuum force, even terminated and then restored, indicating a highly-controlled optical switch. Our result addresses the possibility of designing exotic optical nano-devices by harnessing the power of vacuum.

New diagnostic methods have provided a promising solution for rapid and reliable detection of drug-resistant TB strains. The aim of this study was to evaluate the performance of the MeltPro TB assay in identifying multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) patients from sputum samples. The MeltPro TB assay was evaluated using sputum samples from 2057 smear-positive TB patients. Phenotypic Mycobacterial Growth Indicator Tube (MGIT) 960 drug susceptibility testing served as a reference standard. The sensitivity of the MeltPro TB assay was 94.2% for detecting resistance to rifampicin and 84.9% for detecting resistance to isoniazid. For second-line drugs, the assay showed a sensitivity of 83.3% for ofloxacin resistance, 75.0% for amikacin resistance, and 63.5% for kanamycin resistance. However, there was a significant difference for detecting kanamycin resistance between the two pilot sites in sensitivity, which was 53.2% in Guangdong and 81.5% in Shandong (P = 0.015). Overall, the MeltPro TB assay demonstrated good performance for the detection of MDR- and XDR-TB, with a sensitivity of 86.7% and 71.4%, respectively. The MeltPro TB assay is an excellent alternative for the detection of MDR- and XDR-TB cases in China, with high accuracy, short testing turn-around time, and low unit price compared with other tests.

Sprouty (Spry) proteins have been implicated in cancer progression, but their role in triple-negative breast cancer (TNBC), a subtype of lethal and aggressive breast cancer, is unknown. Here, we reported that Spry1 is significantly expressed in TNBC specimen and MDA-MB-231 cells. To understand Spry1 regulation of signaling events controlling breast cancer phenotype, we used lentiviral delivery of human Spry1 shRNAs to suppress Spry1 expression in MDA-MB-231, an established TNBC cell line. Spry1 knockdown MDA-MB-231 cells displayed an epithelial phenotype with increased membrane E-cadherin expression. Knockdown of Spry1 impaired MDA-MB-231 cell migration, Matrigel invasion, and anchorage-dependent and -independent growth. Tumor xenografts originating from Spry1 knockdown MDA-MB-231 cells grew slower, had increased E-cadherin expression, and yielded fewer lung metastases compared to control. Furthermore, suppressing Spry1 in MDA-MB-231 cells impaired the induction of Snail and Slug expression by EGF, and this effect was associated with increased EGFR degradation and decreased EGFR/Grb2/Shp2/Gab1 signaling complex formation. The same phenotype was also observed in the TNBC cell line MDA-MB-157. Together, our results show that unlike in some tumors, where Spry may mediate tumor suppression, Spry1 plays a selective role in at least a subset of TNBC to promote the malignant phenotype via enhancing EGF-mediated mesenchymal phenotype.

Bacteriophages and their hosts are continuously engaged in evolutionary competition. Here we isolated a lytic phage phiYe-F10 specific for Yersinia enterocolitica serotype O:3. We firstly described the phage receptor was regulated by DTDP-rhamnosyl transferase RfbF, encoded within the rfb cluster that was responsible for the biosynthesis of the O antigens. The deletion of DTDP-rhamnosyl transferase RfbF of wild type O:3 strain caused failure in phiYe-F10 adsorption; however, the mutation strain retained agglutination with O:3 antiserum; and complementation of its mutant converted its sensitivity to phiYe-F10. Therefore, DTDP-rhamnosyl transferase RfbF was responsible for the phage infection but did not affect recognition of Y. enterocolitica O:3 antiserum. Further, the deletions in the putative O-antigen biosynthesis protein precursor and outer membrane protein had no effect on sensitivity to phiYe-F10 infection. However, adsorption of phages onto mutant HNF10-ΔO-antigen took longer time than onto the WT, suggesting that deletion of the putative O-antigen biosynthesis protein precursor reduced the infection efficiency.

Th17 cells have been confirmed to increase neutrophils through cytokine secretions. ALI/ARDS are characterized as neutrophil infiltration in inflammation cases; however, there is conflicting information concerning the role of Th17 cells in ALI/ARDS, as well as their potential treatment value. We measured Th17-linear cytokines in the plasma of patients with sepsis-related ARDS. The consistently high levels of IL-17 and IL-22 in the nonsurvivors suggested that overreaction of the Th17-mediated immune response may be a risk factor for poor outcomes. Th17 linear cytokines were also increased in an LPS-induced murine model of acute lung injury, along with neutrophil accumulation. The mice that completely lacked IL-17 failed to accumulate and activate neutrophils. Lung inflammation was obviously attenuated in the IL-17(-)/(-) mice. Meanwhile, the neutrophil count was markedly increased in the healthy WT mice challenged with recombinant IL-22 and IL-17. Rapamycin attenuated lung injury by inhibiting the differentiation of Th17 cells through RORγt and STAT3 dysfunction. Furthermore, we demonstrated that SOCS3 and Gfi1, which were responsible for the molecular suppression of RORγt and STAT3, were up-regulated by rapamycin. These results point toward a pivotal view to treatment of ALI through weakening the proliferation of Th17 cells with rapamycin.

Staphylococcus aureus causes serious sepsis and necrotic pneumonia worldwide. Due to the spread of multidrug-resistant strains, developing an effective vaccine is the most promising method for combating S. aureus infection. In this study, based on the immune-dominant areas of the iron surface determinant B (IsdB) and clumping factor A (ClfA), we designed the novel chimeric vaccine IsdB151-277ClfA33-213 (IC). IC formulated with the AlPO4 adjuvant induced higher protection in an S. aureus sepsis model compared with the single components alone and showed broad immune protection against several clinical S. aureus isolates. Immunisation with IC induced strong antibody responses. The protective effect of antibodies was demonstrated through the opsonophagocytic assay (OPA) and passive immunisation experiment. Moreover, this new chimeric vaccine induced Th1/Th17-skewed cellular immune responses based on cytokine profiles and CD4(+) T cell stimulation tests. Neutralisation of IL-17A alone (but not IFN-γ) resulted in a significant decrease in vaccine immune protection. Finally, we found that IC showed protective efficacy in a pneumonia model. Taken together, these data provide evidence that IC is a potentially promising vaccine candidate for combating S. aureus sepsis and pneumonia.

MicroRNAs (miRNAs) have been identified as important post-transcriptional regulators involved in various biological and pathological processes of cells, but their underlying mechanisms in chemosensitivity and metastasis have not been fully elucidated. The objective of this study was to identify miR-181b and its mechanism in the chemosensitivity and metastasis of NSCLC. We found that miR-181b expression levels were lower in A549/DDP cells compared with A549 cells. Functional assays showed that the overexpression of miR-181b inhibited proliferation, enhanced chemosensitivity to DDP, attenuated migration and metastatic ability in NSCLC cell lines in vitro and in vivo. TGFβR1 was subsequently identified as a novel functional target of miR-181b. TGFβR1 knockdown revealed similar effects as that of ectopic miR-181b expression, whereas overexpression of TGFβR1 rescued the function of miR-181b-mediated growth, chemosensitivity and metastasis in NSCLC cells. In addition, miR-181b could inactivate the TGFβR1/Smad signaling pathway. We also observed that decreased miR-181b expression and increased TGFβR1 expression were significantly associated with chemosensitivity to DDP and tumor metastasis in NSCLC patients. Consequently, miR-181b functions as a tumor suppressor and has an important role in proliferation, chemosensitivity to DDP and metastasis of NSCLC by targeting TGFβR1/Smad signaling pathway.

Cutaneous wounds are among the most common soft tissue injuries. Wounds involving dermis suffer more from outside influence and higher risk of chronic inflammation. Therefore the appearance and function restoration has become an imperative in tissue engineering research. In this study, cell-aggregates constructed with green fluorescent protein-expressing (GFP(+)) rat bone marrow mesenchymal stem cells (BMMSCs) were applied to rat acute full-layer cutaneous wound model to confirm its pro-regeneration ability and compare its regenerative efficacy with the currently thriving subcutaneous and intravenous stem cell administration strategy, with a view to sensing the advantages, disadvantages and the mechanism behind. According to results, cell-aggregates cultured in vitro enjoyed higher expression of several pro-healing genes than adherent cultured cells. Animal experiments showed better vascularization along with more regular dermal collagen deposition for cell-aggregate transplanted models. Immunofluorescence staining on inflammatory cells indicated a shorter inflammatory phase for cell-aggregate group, which was backed up by further RT-PCR. The in situ immunofluorescence staining manifested a higher GFP(+)-cell engraftment for cell-aggregate transplanted models versus cell administered ones. Thus it is safe to say the BMMSCs aggregate could bring superior cutaneous regeneration for full layer cutaneous wound to BMMSCs administration, both intravenous and subcutaneous.

Staphylococcus aureus (S. aureus) is an opportunistic bacterial pathogen responsible for a diverse spectrum of human diseases, resulting in considerable yearly mortality rates. Due to its rapid acquisition of antibiotic resistance, it becomes increasingly difficult to cure S. aureus infections with conventional antibiotics. Immunotherapy represents a promising alternative strategy to prevent and/or treat the infection. In the present study, passive immunization with polyclonal antibodies targeting three possible S. aureus antigens, Hla, SEB and MntC (termed "SAvac-pcAb") after challenge with lethal dose of S. aureus resulted in reduced bacterial loads, inflammatory cell infiltration and decreased pathology, and was able to provide nearly complete protection in a murine sepsis model. In vitro studies confirmed the direct interaction of SAvac-pcAb with S. aureus bacteria. Additional studies validated that SAvac-pcAb contained both opsonic and neutralizing antibodies that contributed to its protective efficacy. The former mediated opsonophagocytosis in a neutrophil-dependent manner, while the later inhibited the biological functions of Hla and SEB, two major virulence factors secreted by S. aureus. Critically, we demonstrated that SAvac-pcAb was cross-reactive with different clinical strains of S. aureus. These results confirmed the efficacy for treatment of S. aureus infection by passive immunization as an important therapeutic option.