Challenges and recent advances in MOF-based gas separation membranes.

Membrane-based gas separation, characterized by a small footprint, low energy consumption and no pollution, has gained widespread attention as an environmentally friendly alternative to traditional gas separation. Metal-organic-frameworks (MOFs) are considered to be one of the most promising membrane-based gas separation materials because of their large specific surface area and high porosity. One of the hottest studies at the moment is how to utilize the characteristics of MOFs to prepare higher performance gas separation membranes. This paper provides a review of gas separation membranes used in recent years. Firstly, the synthesis methods of MOFs and MOF membranes are briefly introduced. Then, methods to improve the membrane properties of MOFs are described in detail, and include applications of lamellar MOFs, ionic liquid (IL) spin coating, functionalization of MOFs, defect engineering and mixed fillers. In addition, the challenges of MOF-based gas separation membranes are presented, including pore size, environmental disturbances, plasticization, interfacial compatibility, and so on. Finally, based on the current development status of the MOF membranes, the development prospects of MOF gas separation membranes are discussed. It is hoped to provide reliable and complete ideas for researchers to prepare high-performance gas separation membranes in the future.

Single-dose Administration of Recombinant Human Thrombopoietin Enhances Survival and Hematopoietic Reconstruction in Canines Irradiated with 3 Gy Gamma Radiation.

We conducted this study to investigate the radioprotective effects of recombinant human thrombopoietin (rhTPO) on beagle dogs irradiated with 3.0 Gy 60Co gamma rays. Fifteen healthy adult beagles were randomly assigned to a control group with alleviating care, and 5 and 10 µg/kg rhTPO treatment group. All animals received total-body irradiation using 60Co γ-ray source at a dose of 3.0 Gy (dose rate was 69.1 cGy/min). The treatment group received intramuscular injection of rhTPO 5 and 10 µg/kg at 2 h postirradiation, and the control group was administrated the same volume of normal saline. The survival rate, clinical signs, peripheral hemogram, serum biochemistry, and histopathological examination of animals in each group were assessed. Single administration of 10 µg/kg rhTPO at 2 h postirradiation promoted the recovery of multilineage hematopoiesis and improved the survival rate of beagles irradiated with 3 Gy 60Co γ rays. The administration of 10 µg/kg rhTPO alleviated fever and bleeding, reduced the requirement for supportive care, and may have mitigated multiple organ damage.

Minimally invasive delivery of human umbilical cord-derived mesenchymal stem cells by an injectable hydrogel via Diels-Alder click reaction for the treatment of intrauterine adhesions.

Intrauterine adhesions (IUA) are the most common cause of uterine infertility, and conventional treatments have not consistently achieved satisfactory pregnancy rates. Stem cell therapy shows promising potential for the clinical treatment of IUA. Although various advanced biomaterials have been designed for delivering stem cells to the uterine cavity, there remain significant challenges, particularly in devising therapeutic strategies for clinical application that minimize surgical incisions and conform to the intricate structure of uterine cavity. Herein, an injectable hydrogel loaded with human umbilical cord-derived mesenchymal stem cells (UCMSCs) was synthesized via the Diels-Alder click reaction for endometrial regeneration and fertility restoration, exhibiting suitable mechanical properties, good biocompatibility, and desirable degradation properties. Notably, this hydrogel permitted minimally invasive administration and integrated seamlessly with surrounding tissue. Our study revealed that the UCMSCs-laden injectable hydrogel enhanced cell proliferation, migration, angiogenesis, and exhibited anti-fibrotic effects in vitro. The implantation of this hydrogel significantly facilitated endometrium regeneration and restored fertility in a rat endometrial damage model. Mechanistically, in vivo results indicated that the UCMSCs-laden injectable hydrogel effectively promoted macrophage recruitment and facilitated M2 phenotype polarization. Collectively, this hydrogel demonstrated efficacy in regenerating damaged endometrium, leading to the restoration of fertility. Consequently, it holds promise as a potential therapeutic strategy for endometrial damage and fertility decline arising from intrauterine adhesions. STATEMENT OF SIGNIFICANCE: Severe endometrial traumas frequently lead to intrauterine adhesions and subsequent infertility. Stem cell therapy shows promising potential for the clinical treatment of IUA; however, challenges remain, including low delivery efficiency and compromised stem cell activity during the delivery process. In this study, we fabricated an injectable hydrogel loaded with UCMSCs via the Diels-Alder click reaction, which exhibited unique bioorthogonality. The in situ-gelling hydrogels could be introduced through a minimally invasive procedure and adapt to the intricate anatomy of the uterus. The UCMSCs-laden injectable hydrogel promoted endometrial regeneration and fertility restoration in a rat endometrial damage model, efficaciously augmenting macrophage recruitment and promoting their polarization to the M2 phenotype. The administration of UCMSCs-laden injectable hydrogel presents a promising therapeutic strategy for patients with severe intrauterine adhesion.

Development and validation of a machine learning model to predict prognosis in HIV-negative cryptococcal meningitis patients: a multicenter study.

PURPOSE: To predict prognosis in HIV-negative cryptococcal meningitis (CM) patients by developing and validating a machine learning (ML) model. METHODS: This study involved 523 HIV-negative CM patients diagnosed between January 1, 1998, and August 31, 2022, by neurologists from 3 tertiary Chinese centers. Prognosis was evaluated at 10 weeks after the initiation of antifungal therapy. RESULTS: The final prediction model for HIV-negative CM patients comprised 8 variables: Cerebrospinal fluid (CSF) cryptococcal count, CSF white blood cell (WBC), altered mental status, hearing impairment, CSF chloride levels, CSF opening pressure (OP), aspartate aminotransferase levels at admission, and decreased rate of CSF cryptococcal count within 2 weeks after admission. The areas under the curve (AUCs) in the internal, temporal, and external validation sets were 0.87 (95% CI 0.794-0.944), 0.92 (95% CI 0.795-1.000), and 0.86 (95% CI 0.744-0.975), respectively. An artificial intelligence (AI) model was trained to detect and count cryptococci, and the mean average precision (mAP) was 0.993. CONCLUSION: A ML model for predicting prognosis in HIV-negative CM patients was built and validated, and the model might provide a reference for personalized treatment of HIV-negative CM patients. The change in the CSF cryptococcal count in the early phase of HIV-negative CM treatment can reflect the prognosis of the disease. In addition, utilizing AI to detect and count CSF cryptococci in HIV-negative CM patients can eliminate the interference of human factors in detecting cryptococci in CSF samples and reduce the workload of the examiner.

Two-dimensional nanomaterial MXenes for efficient gas separation: a review.

Transition metal carbides/nitrides (MXenes) are emerging two-dimensional (2D) materials that have been widely investigated in recent years. In general, these materials can be obtained from MAX phase ceramics after intercalation, etching, and exfoliation to obtain multilayer MXene nanosheet structures; moreover, they have abundant end-group functional groups on their surface. In recent years, the excellent high permeability, fine sieving ability and diverse processability of MXene series materials make the membranes prepared using them particularly suitable for membrane-based separation processes in the field of gas separation. 2D membranes enhance the diversity of the pristine membrane transport channels by regulating the gas transport channels through in-plane pores (intrinsic defects), in-plane slit-like pores, and planar to planar interlayer channels, endowing the membrane with the ability to effectively sieve gas energy efficiently. Herein, we review MXenes, a class of 2D nanomaterials, in terms of their unique structure, synthesis method, functionalization method, and the structure-property relationship of MXene-based gas separation membranes and list examples of MXene-based membranes used in the field of gas separation. By summarizing and analyzing the basic properties of MXenes and demonstrating their unique advantages compared to other 2D nanomaterials, we lay a foundation for the discussion of MXene-based membranes with outstanding carbon dioxide (CO2) capture performance and outline and exemplify the excellent separation performances of MXene-based gas separation membranes. Finally, the challenges associated with MXenes are briefly discussed and an outlook on the promising future of MXene-based membranes is presented. It is expected that this review will provide new insights and important guidance for future research on MXene materials in the field of gas separation.

[Therapeutic Effect of Single Intramuscular Administration of Recombinant Human Thrombopoietin on Rhesus Monkeys with Acute radiation Sickness].

OBJECTIVE: To confirm the therapeutic effect of recombinant human thrombopoietin (rhTPO) on rhesus monkeys irradiated with 5.0 Gy 60Co γ-ray, and provide experimental basis for clinical treatment of similar patients. METHODS: Fourteen adult rhesus monkeys were irradiated with 60Co γ-ray on both sides at the dose of 5.0 Gy (dose rate 69.2 cGy/min) to establish the acute radiation sickness model. The monkeys were divided into irradiation group (n=5), rhTPO 5 µg/kg group (n=4) and rhTPO 10 µg/kg group (n=5). Two hours after irradiation, the three groups of monkeys were injected with saline 0.1 ml/kg, rhTPO 5 µg/kg（0.1 ml/kg） and rhTPO 10 µg/kg(0.2 ml/kg), respectively. The general signs, survival, peripheral hemogram and serum biochemistry of rhesus monkeys were observed before and after irradiation, and the differences between rhTPO group and irradiation control group were compared. RESULTS: After total body irradiation with 5.0 Gy60Co γ-ray, rhesus monkeys successively showed fever, hemorrhage, sharp decrease of whole blood cell counts in peripheral blood and disorder of serum biochemical indexes. Compared with the irradiated control group, a single intramuscular injection of rhTPO 5 µg/kg or 10 µg/kg 2 hours after irradiation could improve the symptoms of fever and bleeding, increase the nadir of peripheral red blood cells and platelets counts, shorten the duration of hemocytopenia, and advance the time for blood cells to return to the pre-irradiation level. The serum biochemical results showed that rhTPO could improve the abnormality of serum biochemical indexes in rhesus monkeys induced by 5.0 Gy total body irradiation to some extent. Compared with the two administration groups, the therapeutic effect of rhTPO 10 µg/ kg was better. CONCLUSION: A single injection of rhTPO 5 µg/ kg or 10 µg/ kg 2 hours after irradiation can alleviate the injury of multilineage hematopoiesis and promote the recovery in monkeys irradiated by 5.0 Gy γ-ray. It also improves animal signs and has obvious therapeutic effect on acute radiation sickness.

Atg9A-mediated mitophagy is required for decidual differentiation of endometrial stromal cells.

Endometrial decidualization is the foundation of a healthy pregnancy. Mitochondrial dysfunction is an independent cause of disease for energy-intensive organs. Mitochondrial homeostasis plays a key role in the differentiation processes of many cell types. We showed increased activation of mitophagy (mitochondrial autophagy) in the decidua compared with proliferative or secretory endometrium. To better comprehend the mechanisms underlying healthy conception, understanding the mechanism of endometrial stromal cell decidualization is of great importance. Here, we artificially induced decidualization of a human endometrial stromal cell line (T HESCs) and characterized subsequent activation of mitophagy using immunofluorescence assay, electron microscopy and Western blot assay. Knockdown of autophagy-related 9A (ATG9A) led to an obvious reduction of mitophagy and deficiencies in decidualization. Our findings demonstrate a key role for proper mitochondrial dynamics in decidual differentiation and identify ATG9A-mediated mitophagy as a novel therapeutic target for repeated implantation failure or recurrent abortion.

[Effect of Interleukin-6 Gene Deletion on Radiation-Induced Mouse Hematopoietic Injury and Relative Mechanism].

OBJECTIVE: To study the effect of interleukin-6 (IL-6) gene deletion on radiation-induced hematopoietic injury in mice and relative mechanism. METHODS: Before and after whole body 60Co γ-ray irradiation, it was analyzed and compared that the difference of peripheral hemogram, bone marrow hematopoietic stem and progenitor cells conts in IL-6 gene knockout (IL-6-/-) and wild-type (IL-6+/+) mice and serum IL-6 and G-CSF expression levels in above- mentioned mouse were detected. Moreover, 30 days survival rate of IL-6-/- and IL-6+/+ mice after 8.0 Gy γ-ray irradiation were analyzed. RESULTS: IL-6 levels in serum of IL-6+/+ and IL-6-/- mice were respectively (98.95±3.85) pg/ml and (18.36±5.61) pg/ml, which showed a significant statistical differences (P<0.001). There were no significant differences of peripheral blood cell counts and G-CSF level in serum between IL-6+/+ and IL-6-/- mice before irradiation (P>0.05). However, the number of leukocytes, neutrophils, lymphocytes, monocytes, platelets in peripheral blood and G-CSF level in serum of IL-6-/- mice were significantly decreased at 6 h after 8.0 Gy γ-ray irradiation compared with that of IL-6+/+ mice. On days 30 after 8.0 Gy γ-ray irradiation, the survival rate of IL-6+/+ and IL-6-/- mice was 62.5% and 12.5%, and the mean survival time of dead mice was 16.0±1.0 and 10.6±5.3 days, respectively. On days 14 after 6.5 Gy γ-ray irradiation, bone marrow nucleated cells in IL-6+/+ and IL-6-/- mice were respectively (10.0±1.2)×106 and (8.3±2.2)×106 per femur. Compared with IL-6+/+ mice, the proportion of Lin-Sca-1-c-kit+ (LK) in bone marrow of IL-6-/- mice had no significant change (P>0.05), but the proportion of Lin-Sca-1+c-kit+ (LSK) was significantly decreased (P<0.05). CONCLUSION: IL-6 plays an obvious role in regulating hematopoietic radiation injury, and IL-6 deficiency can inhibit the radiation-induced increase of endogenous G-CSF level in serum, aggravates the damage of mouse hematopoietic stem cells（HSC） and the reduction of mature blood cells in peripheral blood caused by ionizing irradiation, resulting in the shortening of the survival time and significant decrease of the survival rate of mice exposed to lethal dose radiation.

A prediction model for bacteremia and transfer to intensive care in pediatric and adolescent cancer patients with febrile neutropenia.

Febrile neutropenia (FN) is a common condition in children receiving chemotherapy. Our goal in this study was to develop a model for predicting blood stream infection (BSI) and transfer to intensive care (TIC) at time of presentation in pediatric cancer patients with FN. We conducted an observational cohort analysis of pediatric and adolescent cancer patients younger than 24 years admitted for fever and chemotherapy-induced neutropenia over a 7-year period. We excluded stem cell transplant recipients who developed FN after transplant and febrile non-neutropenic episodes. The primary outcome was onset of BSI, as determined by positive blood culture within 7 days of onset of FN. The secondary outcome was transfer to intensive care (TIC) within 14 days of FN onset. Predictor variables include demographics, clinical, and laboratory measures on initial presentation for FN. Data were divided into independent derivation (2009-2014) and prospective validation (2015-2016) cohorts. Prediction models were built for both outcomes using logistic regression and random forest and compared with Hakim model. Performance was assessed using area under the receiver operating characteristic curve (AUC) metrics. A total of 505 FN episodes (FNEs) were identified in 230 patients. BSI was diagnosed in 106 (21%) and TIC occurred in 56 (10.6%) episodes. The most common oncologic diagnosis with FN was acute lymphoblastic leukemia (ALL), and the highest rate of BSI was in patients with AML. Patients who had BSI had higher maximum temperature, higher rates of prior BSI and higher incidence of hypotension at time of presentation compared with patients who did not have BSI. FN patients who were transferred to the intensive care (TIC) had higher temperature and higher incidence of hypotension at presentation compared to FN patients who didn't have TIC. We compared 3 models: (1) random forest (2) logistic regression and (3) Hakim model. The areas under the curve for BSI prediction were (0.79, 0.65, and 0.64, P < 0.05) for models 1, 2, and 3, respectively. And for TIC prediction were (0.88, 0.76, and 0.65, P < 0.05) respectively. The random forest model demonstrated higher accuracy in predicting BSI and TIC and showed a negative predictive value (NPV) of 0.91 and 0.97 for BSI and TIC respectively at the best cutoff point as determined by Youden's Index. Likelihood ratios (LRs) (post-test probability) for RF model have potential utility of identifying low risk for BSI and TIC (0.24 and 0.12) and high-risk patients (3.5 and 6.8) respectively. Our prediction model has a very good diagnostic performance in clinical practices for both BSI and TIC in FN patients at the time of presentation. The model can be used to identify a group of individuals at low risk for BSI who may benefit from early discharge and reduced length of stay, also it can identify FN patients at high risk of complications who might benefit from more intensive therapies at presentation.

GNAQ mutation R183Q as a potential cause of familial Sturge-Weber syndrome: A case report.

Sturge-Weber syndrome (SWS) is a rare neurocutaneous disorder whose etiology remains unclear. To investigate the genetic contribution underlying this disease, the genetic variants of a 4-generation family with a history of SWS was analyzed in the present study. SWS was diagnosed in 3 of the family members (II-1, III-11 and IV-6). Sanger sequencing was performed to identify mutations in G protein subunit αq (GNAQ) and RAS p21 protein activator 1 exons in the 3 patients with SWS and other unaffected family members. Notably, a non-synonymous single-nucleotide variant at codon 183 on exon 4 of the GNAQ gene was identified as the only pathogenic site. This variant generated a substitution of arginine (R) with glutamine and resulted in a change of function of the encoded protein. Evolutionary conservation analysis revealed that the mutated residue 183 (R) of GNAQ is highly conserved across several vertebrate species. Furthermore, an immunofluorescence staining assay demonstrated that the substitution of arginine with glutamine resulted in a change in the sub-cellular localization of the GNAQ recombinant protein in vitro. These findings may aid in the development of novel diagnostic markers and/or therapeutic targets for the treatment of patients with familial SWS.