Combined biochar and wheat-derived endophytic bacteria reduces cadmium uptake in wheat grains in a metal-polluted soil.

In this study, two wheat-derived cadmium (Cd)-immobilizing endophytic Pseudomonas paralactis M14 and Priestia megaterium R27 were evaluated for their effects on wheat tissue Cd uptake under hydroponic conditions. Then, the impacts of the biochar (BC), M14+R27 (MR), and BC+MR treatments on wheat Cd uptake and the mechanisms involved were investigated at the jointing, heading, and mature stages of wheat plants under field-plot conditions. A hydroponic experiment showed that the MR treatment significantly decreased the above-ground tissue Cd content compared with the M14 or R27 treatment. The BC+MR treatment reduced the grain Cd content by 51.5%-67.7% and Cd translocation factor at the mature stage of wheat plants and increased the organic matter-bound Cd content by 31%-75% in the rhizosphere soils compared with the BC or MR treatment. Compared with the BC or MR treatment, the relative abundances of the biomarkers associated with Gemmatimonas, Altererythrobacter, Gammaproteobacteria, Xanthomonadaceae, Phenylobacterium, and Nocardioides in the BC+MR-treated rhizosphere microbiome decreased and negatively correlated with the organic matter-bound Cd contents. In the BC+MR-treated root interior microbiome, the relative abundance of the biomarker belonging to Exiguobacterium increased and negatively correlated with the Cd translocation factor, while the relative abundance of the biomarker belonging to Pseudonocardiaceae decreased and positively correlated with the Cd translocation factor. Our findings suggested that the BC+MR treatment reduced Cd availability and Cd transfer through affecting the abundances of these specific biomarkers in the rhizosphere soil and root interior microbiomes, leading to decreased wheat grain Cd uptake in the contaminated soil.

Efficacy Analysis of Temporary Spinal Cord Stimulation in the Treatment of Refractory Postherpetic Neuralgia.

BACKGROUND: Spinal cord stimulation can be considered in PHN patients if conservative treatment is not effective. However, the long-term pain outcomes of temporary (7-14 days) spinal cord stimulation (tSCS) in refractory PHN patients with a course of more than 3 months have not been  documented. OBJECTIVES: To investigate the efficacy of tSCS as a treatment for refractory PHN. STUDY DESIGN: Retrospective study. SETTING: Pain Department in a university hospital. METHODS: A total of 52 patients with refractory PHN were treated with tSCS between March 2018 and February 2021. Their medical records were collected, and the patients were divided into 3 groups according to the course of their disease into the medium-term group, long-term group and ultra-long-term group. The changes in the numeric rating scale (NRS) scores, Pittsburgh sleep quality index (PSQI) responses, pain relief rate, postoperative efficiency and patients' use of analgesics were recorded before the operation, 3 days, 10 days, one month, 3 months, 6 months and 12 months after the operation. RESULTS: The average NRS scores, the maximum NRS scores and the PSQI scores at 3 days, 10 days, one month, 3 months, 6 months and 12 months after the operation were significantly lower than those before the operation (P < 0.05). The average NRS scores and the maximum NRS scores of all groups increased significantly from one month to 6 months compared to those at 10 days after the tSCS treatment, and they decreased significantly at 12 months compared with 6 months post-operation. The average NRS scores of the medium-term and long-term group were significantly lower than that of the ultra-long-term group at 1-3 months after the operation, and the maximum NRS scores at one month, 3 months and 12 months after the operation were also significantly lower in the medium-term and long-term group compared to the ultra-long-term group. The average PSQI scores at 1-12 months after the operation were not significantly higher than that at 10 days after the operation, but it decreased significantly at 12 months compared with 6 months after the operation. Among the 3 groups, the PSQI scores of the medium-term and long-term group were significantly lower than those of the ultra-long-term group at 6 months after the operation. The postoperative pain relief rate ranged from 41.51%-59.81%, and the total effective rate was 42.31%-69.23%, and there was no significant difference among the 3 groups. Some patients still needed analgesics at 12 months after the operation, but the number of patients who were taking medications post-operation was significantly lower than that before the operation. LIMITATIONS: This is a single-center retrospective study with the inability to completely control for variables. Additionally, the number of cases is small and the follow-up duration is short. CONCLUSION: tSCS can be used as a safe and effective method to relieve refractory PHN, and the curative effect is substantially higher in patients with a disease course of 3-12 months compared to that in patients with a course of more than 12 months.

Global burden and incidence trends of zika virus infection among women aged 15-49 years from 2011 to 2021: A systematic analysis.

BACKGROUND: Zika virus (ZIKV) infection during pregnancy presents a significant health risk in women of reproductive age and their offspring due to severe neurological complications. It is meaningful to assess its global burden and temporal trends. METHODS: This study extracted annual incidence cases and rates of ZIKV among women of reproductive age (15-49 years) between 2011 and 2021 from Global Burden of Diseases (GBD) 2021, including global level, 21 GBD regions, 5 socio-demographic index (SDI) regions, 7 age groups, and 204 countries and territories. Relative percent change in cases and estimated annual percentage change (EAPC) of incidence rates were used to quantify the temporal trends. RESULTS: The incidence rate of ZIKV infection exhibited a pronounced peak in 2016 at 174.27 per 100,000 population, with an EAPC of 158.30 % from 2011 to 2016 and -51.86 % from 2016 to 2021 at 3.06 per 100,000 population. And only 5 out of the 21 GBD regions reported ZIKV infection in 2021, predominantly concentrated in Latin America and Caribbean. The outbreaks were primarily concentrated in low-middle and middle SDI regions. In 2021, at the global level, the incidence rates of ZIKV infection among women of reproductive age were similar across different age groups, ranging from 2.41 to 3.39 per 100,000 population. The proportion of ZIKV infection cases was slightly higher in women aged 25-29 and 30-34 years compared to other age groups in 2021, whereas a higher proportion of cases were observed in younger age groups in 2011 and 2016. CONCLUSIONS: Women of reproductive age in Latin America and Caribbean continue to face the threat of ZIKV. Regions with lower SDI had a disproportionately severe burden. Future public health strategies should focus on high-risk areas and populations of reproductive age, enhancing surveillance, prevention, and education efforts to further mitigate the public health threat posed by ZIKV.

Screening of prognostic factors and survival analysis based on histological type for perimenopausal endometrial carcinoma treated with hysterectomy.

PURPOSE: This study aimed to explore the prognostic factors and survival patterns based on the histological type for the perimenopausal endometrial carcinoma (PIPEC) patients treated with hysterectomy. METHODS: The PIPEC patients were selected from the Surveillance, Epidemiology, and End Results (SEER) database. Methods of random survival forest (RSF) and Cox regression were used to identify the possible prognostic factors of PIPEC patients. Then overall survival (OS) and cancer-specific survival (CSS) of PIPEC data were analyzed by histological types with regional lymph nodes status and SEER-stage to investigate the survival patterns of the PIPEC patients. RESULTS: A total of 14,178 PIPEC patients were included in the study. We found tumor size, grade, histology, SEER-stage, AJCC-stage, AJCC-T stage, metastasis to distant organs and regional lymph nodes status had a significant survival outcome for PIPEC both for OS and CSS (all p < 0.05). Regardless of regional lymph nodes status and SEER-stage for OS and CSS, the low-grade endometrioid carcinoma had the best prognosis outcome, followed by the mix cell adenocarcinoma and high-grade endometrioid carcinoma, while the carcinosarcoma and undifferentiated carcinoma had relatively poor prognosis outcome. And the survival patterns of different histological types of PIPEC were diverse and changed along with the time. CONCLUSION: We identified the possible prognostic factors of PIPEC patients treated with hysterectomy. And survival analysis based on the regional lymph nodes status and SEER-stage revealed the different histological types of PIPEC had diverse survival patterns, which will be helpful for guiding clinical practice.

Activating Metal-Organic Cages by Incorporating Functional M(ImPhen)3 Metalloligands: From Structural Design to Applications.

ConspectusThe emulation of ingenious biofunctions has been a research focus for several decades. Metal-organic cages (MOCs), as a type of discrete supramolecular assembly with well-defined shapes and cavities, have aroused great interest in chemists to imitate natural protein cages or enzymes. However, to genuinely achieve tailored functionalities or reactivities of enzymes, the design of cage structures combining both the confined microenvironment and the active site is a prerequisite. Therefore, the integration of functionalized motifs into MOCs is expected to provide a feasible approach to construct biofunctional confined nanospaces, which not only allows the modulation of cage properties for applications such as molecular recognition, transport, and catalysis but also creates unique microenvironments that promote enzymatic effects for special reactivities and selectivities, thereby providing a versatile platform to achieve exceptional biomimetic functions and beyond.In this Account, we specifically focus on our research toward engineering active confined-nanospaces in MOCs via incorporation of M(ImPhen)3 metalloligands, a typical tris-chelate coordination moiety comprising imidazophenanthroline ligands and variable metal ions, as the principle functional units for stepwise assembly of active-MOCs. Starting from their structure design and merits, we describe the versatility of M(ImPhen)3 centers for multifunctionalization of the confined cage-nanospaces. By integrating different metal ions like Ru, Os, Fe, Co, Ni, Zn, the metal ion inherent properties, e.g., redox activity of Fe/Co-centers, chirality, and photoactivity of Ru-centers, and dynamics of Co/Zn-centers, could be integrated and tailored on the cages as isostructural nanosized containers or reactors. Changing the Pd or Pt cage vertices to organic clips could remarkably enhance acid-base stability and endow cages with flexibility and allostery. Utilization of ImPhen organic ligands containing imidazole groups introduces proton transfer capability, which can couple with the high-positive charges on the cage to create amphoteric microenvironments in the porous open-cage solution. Moreover, the nonplanar stereoconfiguration of M(ImPhen)3 confers multiple peripheral pockets on the cage, which render multisite, high-order, and dynamics guest binding for the benefit of applications such as drug delivery, molecular separation, and catalytic turnover.The construction of active-MOCs from tailorable M(ImPhen)3 metalloligands provides us with a new perspective on their structural design and functionalities. Merging the cage confinement with distinct physicochemical properties on a supramolecular level makes it practical to realize synergistic and cooperative effects for functionality enhancement beyond molecular components or the reactivity different from the bulky solution, which could largely expand the potential of MOCs as a multirole platform to wide application scenarios such as artificial photosynthesis, unconventional catalysis, and theranostic nanomedicine.

Acoustic Streaming Tunnel Enables Particle Velocity Stretching in Multiplex Flow Cytometry.

Multiplexed flow cytometry, known for its powerful high-throughput identification capability, is widely applied across various biomedical and clinical fields. However, classical flow cytometry relies on multichannel lasers and detectors, which are significant in cost and size, limiting their application in miniaturized assays. Herein, we developed an acoustic streaming-based flow cytometry technique that focuses on multisized microbeads flowing sheathlessly. This method enables the discrimination of particle types and the quantification of target protein concentrations using only a single detector. Microbeads of different sizes exhibit distinct behaviors in the continuous acoustic streaming tunnel, leading to an increased velocity difference during their transition under the laser spot. Consequently, a size detection method based on "velocity stretching" has been established. A multiplex assay of three proteins: cardiac troponin I, creatine kinase-MB and myoglobin, in acute myocardial infarction is performed to validate the feasibility and evaluate the performance of the system. This new multiplexed flow cytometry strategy is expected to enable low-cost and onsite detection of multiple biomarkers.

Fluctuation trend of inflammatory indexes related to gestational diabetes mellitus from second trimester to third trimester of pregnancy.

OBJECTIVE: This study aims to assess the prognostic and diagnostic value of inflammatory indexes related to gestational diabetes mellitus (GDM) from the second trimester to the third trimester of pregnancy. MATERIALS AND METHODS: In this study, we randomly selected 65 pregnant women diagnosed with GDM at our hospital from December 2022 to June 2023 to form the GDM group (n = 65). Additionally, 65 pregnant women at the same gestational weeks without GDM were selected as the Normal group (n = 65). We collected gestational information and serum samples at 24 and 36 weeks of gestation from the participants. The levels of NLRP3, IL-1Ra, and TBP-2 were determined using enzyme-linked immunosorbent assay (ELISA) to explore their changes during pregnancy. Further, this study analyzed the changes in the levels of NLRP3, IL-1Ra, and TBP-2 at 24 and 36 weeks of gestation in GDM patients and their correlation with gestational diabetes mellitus. RESULTS: The study showed that pre-pregnancy body mass index (BMI), neonatal weight, gestational hypertension, and macrosomia are significantly associated with the occurrence of GDM (P < 0.05). Statistical analysis comparing the normal and GDM groups found no significant changes in the levels of NLRP3, IL-1Ra, and TBP-2 with the progression of gestation in the normal group. In contrast, in the GDM group, the levels of IL-1Ra in serum samples at 24 and 36 weeks were significantly increased (P < 0.05) while the levels of NLRP3 and TBP-2 were significantly reduced (P < 0.05). At 36 weeks, there was a positive correlation between the levels of NLRP3, IL-1Ra, and TBP-2. Compared to the normal group, the overall levels of NLRP3, IL-1Ra, and TBP-2 in the GDM group were lower (P < 0.05) and the weight of the newborns was significantly correlated with these three indicators (P < 0.05), specifically newborn weight increased with the levels of NLRP3 and TBP-2 but decreased with the increase of IL-1Ra (P < 0.05). Multifactorial logistic regression analysis further revealed that NLRP3 is an independent factor influencing GDM (P < 0.05). ROC curve analysis of the NLRP3 level at 24 weeks of gestation found that NLRP3 has a good value in predicting GDM (AUC = 0.720, 95%CI 0.630-0.809, P < 0.001) and the combined prediction of NLRP3, IL-1Ra, and TBP-2 also showed a good predictive value for GDM. CONCLUSION: The changes in NLRP3, IL-1Ra, and TBP-2 persisted throughout the 24 to 36 weeks of gestation, playing an important role in predicting the occurrence of GDM and the weight of the newborn.

Anti-oxidant, anti-apoptotic and anti-inflammatory effects of geraniin in spinal cord injury in rat: role of COX-2.

BACKGROUND: Spinal cord injury (SCI) is devastating diseases affecting the degeneration of the spinal column, and vascular problems. However, the currently available therapeutic interventions are insufficient to address the effect of SCI which leads to significant impact on the morbidity and mortality of patients. In the present manuscript, we intend to investigate the pharmacological effect of geraniin on the SCI in Sprague-Dawley (SD) rats. MATERIALS AND METHODS: The SCI in rats were induced by the conventional weight-drop method and treated with GER (2.5, 5, and 10 mg/kg). Subsequently, the locomotor activity of rats with SCI was assessed using Basso, Beattie, and Bresnahan (BBB) scores, while oxidative stress indicators and inflammatory variables were analyzed using commercially available kits. Additionally, neuronal death was quantified using TUNEL labeling. The enzymatic activity of caspase 3, 8, and 9 was also assessed. Furthermore, the expression levels of Bcl2, Bax, and COX-2 in rat spinal cords after SCI were analyzed by RT-PCR analysis. RESULTS: Our research indicated that therapy with GER in a manner that depends on the dosage could enhance the functional recovery, as well as reduce the occurrence of apoptosis, mitigate the inflammatory and oxidative response in rats with SCI. Furthermore, it was observed that GER increased the expression of Bcl2 and decreased the expression of Bax and COX-2. The concentration of caspase-3, -8, and -9 was observed to be decreased in SCI rats treated with GER. CONCLUSIONS: GER might protect the spinal cord from SCI by reducing apoptosis, oxidative stress, and inflammatory response through the inhibition of COX-2.

Hollow Calcium/Copper Bimetallic Amplifier for Cuproptosis/Paraptosis/Apoptosis Cancer Therapy via Cascade Reinforcement of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction.

The endoplasmic reticulum (ER) and mitochondria are essential organelles that play crucial roles in maintaining cellular homeostasis. The simultaneous induction of ER stress and mitochondrial dysfunction represents a promising yet challenging strategy for cancer treatment. Herein, a hollow calcium-copper bimetallic nanoplatform is developed as a cascade amplifier to reinforce ER stress and mitochondrial dysfunction for breast cancer treatment. For this purpose, we report a facile method for preparing hollow CaCO3 (HCC) nanoparticles by regulating the dissolution-recrystallization process of amorphous CaCO3, and the amplifier D@HCC-CuTH is meticulously fabricated by sequentially coating disulfiram-loaded HCC nanoparticles with a copper coordination polymer and hyaluronan. In tumor cells, the dithiocarbamate-copper complex generated in situ by liberated disulfiram and Cu2+ inhibits the ubiquitin-proteasome system, causing irreversible ER stress and intracellular Ca2+ redistribution. Meanwhile, the amplifier induces mitochondrial dysfunction via triggering a self-amplifying loop of mitochondrial Ca2+ burst, and reactive oxygen species augment. Additionally, Cu2+ induces dihydrolipoamide S-acetyltransferase oligomerization in mitochondria, further exacerbating mitochondrial damage via cuproptosis. Collectively, ER stress amplification and mitochondrial dysfunction synergistically induce a cuproptosis-paraptosis-apoptosis trimodal cell death pathway, which demonstrates significant efficacy in suppressing tumor growth. This study presents a paradigm for synchronously inducing subcellular organelle disorders to boost cancer multimodal therapy.

Disease Burden and Geographic Inequalities in 15 Types of Neonatal Infectious Diseases in 131 Low- and Middle-Income Countries and Territories.

Background: The burden of neonatal infections in low- and middle-income countries and territories (LMICs) is a critical public health challenge, while our understanding of specific burden and secular trends remains limited. Methods: We gathered annual data on 15 types of neonatal infections in LMICs from 1990 to 2019 from the Global Burden of Disease 2019. Numbers, rates, percent changes, and estimated annual percentage changes of incidence and deaths were calculated. We also explored the association between disease burden, socio-demographic index (SDI), and universal health coverage index (UHCI). Results: Enteric infections and upper respiratory infections owned the top highest incidence rates for neonates in 2019. Neonatal sepsis and other neonatal infections, as well as otitis media, demonstrated an increasing trend of incidence across all 3 low- and middle-income regions. The top 3 causes of neonatal mortality in 2019 were neonatal sepsis and other neonatal infections, lower respiratory infections, and enteric infections. Between 1990 and 2019, all of the neonatal infection-related mortality rates suggested an overall decline. Sex differences could be found in the incidence and mortality of some neonatal infections, but most disease burdens decreased more rapidly in males. SDI and UHCI were both negatively associated with most of the disease burden, but there were exceptions. Conclusions: Our study serves as a vital exploration into the realities of neonatal infectious diseases in LMICs. The identified trends and disparities not only provide a foundation for future research but also underscore the critical need for targeted policy initiatives to alleviate on a global scale.

Interpenetrating Composite Hydrogel Electrolyte with Organic/Inorganic Polar Groups for Stable Zinc Metal Anode.

Hydrogel electrolytes have been widely explored in flexible zinc batteries owing to their considerable mechanical strain and water-retaining properties. However, it is difficult to balance the contradiction between the ionic conductivity and the mechanical strength due to the deterioration of structural stability with the addition of electrolyte salts. To address this, we designed a coassembling organic-inorganic hydrogel (P-P/M) based on poly(vinyl alcohol)-polyacrylamide (P-P) interpenetrating matrix decorated with Zn-based montmorillonite (Zn-MMT). The Zn-MMT with overall negative potential can attract and regulate the transport of Zn2+, while the Brønsted/Lewis acid sites with positive polarizations offer anchoring sites for anions, which increases the cation transference number and reduces byproduct formation. Moreover, the formation of hydrogen bonds in the hydrogel can weaken the contact between free water molecules and the zinc cations, which effectively suppresses the corrosion of zinc foil. Consequently, the Zn//Zn cell with P-P/M electrolyte delivers a long cycle life of 2400 h at 0.5 mA cm-2. The good mechanical properties of the P-P/M hydrogel boost its application in flexible pouch cells even under bending and cutting conditions. This study provides an effective approach to designing organic-inorganic hydrogel electrolytes for long-life flexible zinc batteries.

Knockdown of BMP7 induced oligodendrocyte apoptosis, demyelination and motor function loss.

BACKGROUND: Demyelinating diseases, including multiple sclerosis (MS) and spinal cord injury (SCI), lead to significant neurological deficits primarily due to the loss of oligodendrocytes (OLs). Bone Morphogenetic Protein 7 (BMP7) is expressed abundantly in the central nervous system and previous studies showed its protective effect in reducing OL loss. In this study, we aim to explore BMP7's potential as a biomarker and therapeutic target for demyelinating diseases by investigating its expression and effects on OLs and myelin sheath integrity. METHOD: We analyzed multiple Gene Expression Omnibus datasets for BMP7 expression profiles in demyelinating conditions such as MS and SCI. Experimentally, we employed a BMP7 knockdown model in rat spinal cords using adeno-associated virus8 vectors to specifically reduce BMP7 expression. Western blotting, immunofluorescence, and Nissl staining were used to assess the effect on OL and other types of cells. The structure of myelin sheath and locomotor function were evaluated using transmission electron microscopy and BBB scores, and statistical analysis included ROC curves and ANOVA to evaluate BMP7's diagnostic and therapeutic potential. RESULTS: BMP7 expression consistently decreased across various demyelinating models, and BMP7 knockdown led to increased OL apoptosis through the Smad1/5/9 pathway, with no apparent effect on other cell types. This reduction in OLs was associated with myelin degeneration, axonal damage, and impaired motor function. CONCLUSION: The study confirms BMP7's significant involvement in the pathophysiology of demyelinating diseases and supports its potential as a therapeutic target or biomarker. Future research should focus on therapeutic strategies to enhance BMP7 function and further investigate the mechanisms by which BMP7 supports myelin integrity.

Feasibility and effectiveness of a foam rolling intervention in pregnant women requiring bed rest for foetal protection: a randomised controlled trial.

BACKGROUND: Bed rest during pregnancy can lead to reduced physical activity, impairing lower limb venous blood flow and increasing the risk of deep vein thrombosis (DVT) and muscle atrophy. We investigated the clinical efficacy of foam rolling intervention (FRI) in enhancing lower limb venous blood flow, mitigating the risk of DVT and muscle atrophy in pregnant women on bed rest. METHODS: This single-blind, randomised controlled trial enrolled 86 pregnant women with long-term bed rest for foetal protection (≥ 7 days), gestational age ≥ 20 weeks, and maternal age < 40 years. Participants were randomly assigned to a control or experimental group using a random number table. The control group received standard care, whereas the experimental group underwent FRI. Researchers and statisticians were aware of the treatment groups, however, the participants were blinded. Lower limb blood flow velocity, D-dimer levels, incidence of DVT, and the extent of lower limb muscle atrophy were assessed in both groups at baseline and post-intervention (day 7). To account for a 5% attrition rate and potential sampling error, the estimated sample size for each experimental and control group was 40. RESULTS: Before the intervention, no significant differences were observed between the experimental and control groups in peak blood flow, mean flow velocity, D-dimer values, or leg circumference (P > 0.05), however, the peak blood velocities of the popliteal veins were significantly higher in the control group (P = 0.031). On the seventh day post-intervention, the experimental group had significantly higher mean and peak blood velocities in femoral and popliteal veins, significantly (P < 0.05), lower mean D-dimer levels (P = 0.035), and a significantly smaller reduction in thigh and calf circumference (P < 0.001). Consequently, the rate of thigh muscle atrophy was significantly slower in the experimental group (P = 0.011). CONCLUSIONS: FRI is an effective intervention for improving lower limb venous blood flow, mitigating the risk of DVT and muscle atrophy in pregnant women on bed rest. TRIAL REGISTRATION: This trial was retrospectively registered with the Chinese Clinical Trial Registry on June 18, 2024 (registration number: ChiCTR2400085770).

Protocol to detect spatio-molecular profiles underlying neuroimaging features in the human cerebellum.

Imaging transcriptomics offers opportunities to uncover the genetic profiles underlying brain imaging-derived phenotypes (IDPs) but lacks explanation from gene to IDPs. Here, we present a protocol for combining imaging transcriptomics with gene set variation analysis (GSVA) to detect spatio-molecular profiles underlying IDPs in the human cerebellum. We describe the steps for data preparation, model training, model evaluation, key gene identification, and GSVA. Our protocol broadens the way to interpret the biological pathways shaping a wide range of neuroimaging-derived cerebellar properties. For complete details on the use and execution of this protocol, please refer to Wang et al.1.

QRICH1 suppresses pediatric T-cell acute lymphoblastic leukemia by inhibiting GRP78.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that commonly affects children and adolescents with a poor prognosis. The terminal unfolded protein response (UPR) is an emerging anti-cancer approach, although its role in pediatric T-ALL remains unclear. In our pediatric T-ALL cohort from different centers, a lower QRICH1 expression was found associated with a worse prognosis of pediatric T-ALL. Overexpression of QRICH1 significantly inhibited cell proliferation and stimulated apoptosis of T-ALL both in vitro and in vivo. Upregulation of QRICH1 significantly downregulated 78 KDa glucose-regulated protein (GRP78) and upregulated CHOP, thus activating the terminal UPR. Co-overexpression of GRP78 in T-ALL cells overexpressing QRICH1 partially reverted the inhibited proliferation and stimulated apoptosis. QRICH1 bound to the residues Asp212 and Glu155 of the nucleotide-binding domain (NBD) of GRP78, thereby inhibiting its ATP hydrolysis activity. In addition, QRICH1 was associated with endoplasmic reticulum (ER) stress in T-ALL, and overexpression of QRICH1 reversed drug resistance. Overall, low QRICH1 expression is an independent risk factor for a poor prognosis of pediatric T-ALL. By inhibiting GRP78, QRICH1 suppresses pediatric T-ALL.

Angelica sinensis polysaccharides ameliorate 5-FU-induced stress anemia via promoting extramedullary erythroblastic island central macrophage-mediated erythroid differentiation.

BACKGROUND: Chronic anemia, especially chemotherapy-induced anemia, is a common and intractable symptom. Puzzlingly, the conventional anemic treatment may lead to various side effects, and the mechanism of stress anemia remains unclear. METHODS: Here, peripheral blood, histopathological and transmission electron microscopical examination, colony forming test, flow cytometry, and qRT-PCR assay were used to investigate the effects of Angelia sinensis polysaccharide (ASP), one main active ingredient of Chinese herb medicine Angelica sinensis, on ameliorating 5-fluorouracil (5-FU)-induced stress anemia. RESULTS: We found that intraperitoneal injection to a C57BL/6J mouse ASP 100 mg/kg per day for consecutive 10 days or 14 days, remarkably accelerated the recovery of RBC, hemoglobin, and hematocrit in blood. ASP alleviated 5-FU-caused impairment of bone marrow cell and BFU-E enumeration. Meanwhile, ASP antagonized 5-FU promoting extramedullary erythropoiesis in the spleen, inducing splenomegaly due to stress erythroblastic islands, and occurrence of megakaryocytes and hematopoietic precursors in splenic colonies. ASP increased splenic stress BFU-E enumeration, driving BFU-E differentiation towards Pro-E and end-stage erythroblasts. Furthermore, ASP increased the number of F4/80+VCAM-1+ splenic erythroblastic island central macrophages, upregulating genetic expression of EPOR, Emp, VCAM-1, Hmox-1, Trf, TfR1, Fpn1, Spi-C, DNase2a, Tim4, MertK, and Klf1 in splenocytes. CONCLUSIONS: Our findings indicate that the possible mechanism of chemotherapy-induced anemia is related to stress erythroid maturation arrest. Whereas, ASP may promote stress erythroid differentiation via elevated EPO sensitivity in extramedullary hematopoietic organs and enhanced macrophage-mediated adhesion, iron homeostasis and transfer, and nuclear engulfment, which may represent a promising therapeutic strategy.

Interaction between economic status and healthy lifestyle in long COVID among Chinese older population: a cross-sectional study.

OBJECTIVES: To estimate the interaction between economic status (ES) and healthy lifestyle in long COVID among Chinese older people infected with SARS-CoV-2. DESIGN: A cross-sectional study based on the Peking University Health Cohort in Anning, Yunnan. SETTING: All primary health institutions in Anning, Yunnan Province, China, from April to May 2023. PARTICIPANTS: A total of 4804 people aged 60 and older infected with SARS-CoV-2 were included in this study. PRIMARY AND SECONDARY OUTCOME MEASURES: Long COVID was measured by participants' self-reported symptoms using structured questionnaires. ES was measured by last-month personal income, and participants' ES was defined as low if their income was below the per capita monthly income of local residents. Lifestyle score was equal to the number of healthy behaviours (including smoking, drinking, weight, exercise and diet) and grouped using the median score as the cut-off point. Univariate and multivariate logistic models were employed to estimate the association of ES with long COVID. Interaction between ES and lifestyle in long COVID was assessed by multiplicative interaction term. RESULTS: We enrolled a total of 4804 participants infected with SARS-CoV-2, of whom 57.3% (2754 of 4804) had at least one long COVID symptom. Fatigue (1546, 56.1%), cough (1263, 45.9%) and muscle pain (880, 32.0%) were the top three common symptoms. Patients with low ES had a 48% (adjusted OR: 1.48; 95% CI 1.22, 1.82) increased risk of long COVID. A significant interaction was observed between ES and lifestyle (p value for interaction <0.001) in long COVID. CONCLUSION: The interaction between ES and healthy lifestyle in long COVID was prominent. Comprehensive strengthened economic support for patients recovering from COVID-19, especially for those with low healthy lifestyle, should be implemented to prevent and manage long COVID symptoms.

Network analysis of anxiety and cognitive impairment among mental healthcare workers.

Introduction: With the rising demand for medical services and the associated burden, work-related stress and mental health issue have garnered increased attention among healthcare workers. Anxiety, cognitive impairment, and their comorbidities severely impact the physical and mental health as well as the work status of healthcare workers. The network analysis method was used to identify the anxiety and cognitive impairment among mental healthcare workers using the Generalized Anxiety Disorder Scale (GAD-7) and the Perceived Deficit Questionnaire for Depression (PDQ-D). We sought to identify the core symptoms associated with the comorbidity of anxiety and cognitive impairment in mental healthcare workers. Methods: The study was conducted by Shandong Daizhuang Hospital and Qingdao Mental Health Center in China from September 13, 2022, to October 25, 2022, involving a total of 680 healthcare workers as participants. GAD-7 and PDQ-D were utilized to assess anxiety and cognitive impairment, respectively. Regularized partial correlation network analysis was employed to examing the expected influence and predictability of each item within the network. Statistical analysis and visualization of the network were performed using R software. Results: The mean total score for anxiety was 3.25, while the mean total score for cognitive symptoms was 15.89. PDQ17 "Remembering numbers", PDQ12 "Trouble get started" and PDQ20 "Trouble make decisions" emerged as central symptoms in the anxiety-cognition network. GAD6 "Irritable", GAD5 "Restlessness" and GAD1 "Nervousness or anxiety" were identified as the most critical bridge symptoms connecting anxiety and cognition. Gender was found to be unrelated to the global strength of the network, edge weight distribution, or individual edge weights. Conclusion: Utilizing central and bridge symptoms (i.e., Remembering numbers, Trouble get started, Trouble make decisions, Irritable, Restlessness and Nervousness or anxiety) as primary intervention points may aid in mitigating the serious health consequences of anxiety, cognitive impairment, and comorbidities anxiety and cognitive impairment for mental healthcare workers.

Possible Mechanism of Sucrose and Trehalose-6-Phosphate in Regulating the Secondary Flower on the Strong Upright Spring Shoots of Blueberry Planted in Greenhouse.

Secondary flowering is the phenomenon in which a tree blooms twice or more times a year. Along with the development of blueberry (Vaccinium corymbosum L.) fruits in spring, a large number of secondary flowers on the strong upright spring shoots were noticed in blueberries planted in the greenhouse. To reveal the cause and possible regulatory mechanism of the phenomenon, we clarified the phenological characteristics of flower bud differentiation and development on the spring shoots by combining phenological phenotype with anatomical observation. Furthermore, the changes in carbohydrates, trehalose-6-phosphate (Tre6P), and the relationship among the key enzyme regulatory genes for Tre6P metabolism and the key regulatory genes for flower formation during the differentiation process of apical buds and axillary buds were investigated. The results showed that the process of flower bud differentiation and flowering of apical and axillary buds was consistent, accompanied by a large amount of carbohydrate consumption. This process was positively correlated with the expression trends of VcTPS1/2, VcSnRK1, VcFT, VcLFY2, VcSPL43, VcAP1, and VcDAM in general, and negatively correlated with that of VcTPP. In addition, there is a certain difference in the differentiation progress of flower buds between the apical and axillary buds. Compared with axillary buds, apical buds had higher contents of sucrose, fructose, glucose, Tre6P, and higher expression levels of VcTPS2, VcFT, VcSPL43, and VcAP1. Moreover, VcTPS1 and VcTPS2 were more closely related to the physiological substances (sucrose and Tre6P) in axillary bud and apical bud differentiation, respectively. It was suggested that sucrose and trehalose-6-phosphate play a crucial role in promoting flower bud differentiation in strong upright spring shoots, and VcTPS1 and VcTPS2 might play a central role in these activities. Our study provided substantial sight for further study on the mechanism of multiple flowering of blueberries and laid a foundation for the regulation and utilization of the phenomenon of multiple flowering in a growing season of perennial woody plants.