Efficacy and safety of CAR-T therapy targeting CLL1 in patients with extramedullary diseases of acute myeloid leukemia.

BACKGROUNDS: The incidence of extramedullary diseases (EMDs) in patients diagnosed with acute myeloid leukemia (AML) is approximately 10-20%. These patients exhibit a significantly distinct etiology, therapeutic response, and prognosis compared to patients without EMDs. CLL1 CAR-T therapy has been demonstrated satisfactory efficacy and safety in the treatment of refractory and relapsed AML patients. However, concerns have been raised regarding the potential impact of extramedullary niduses on the effectiveness of CLL1 CAR-T therapy. METHODS: A total of 47 patients were enrolled in this study, including 27 patients with isolated AML tumor bone marrow infiltration and 20 patients with both extramedullary and bone marrow infiltration of AML. CLL1 CAR-T cells were manufactured and subjected to rigorous quality control in the hematology laboratory of Tianjin First Central Hospital. The efficacy and adverse reactions were assessed following CAR-T cell infusion, while expansion of CAR-T cells, levels of cytokines releasing, and other indicators were closely monitored. RESULTS: Among the 20 patients with EMDs and the 27 individuals without EMDs, complete remission in bone marrow was achieved by 65.00% and 81.48% of patients, respectively. Meanwhile, among the patients with EMDs, 55.00% achieved complete remission while 10.00% achieved partial remission when assessing the efficacy of CLL1 CAR-T cells against extramedullary niduses. Although the overall survival, progression-free survival, and duration of remission period appeared to be shorter for patients with EMDs compared to those without EMDs, this difference did not reach statistical significance. The incidence rates of complications were comparable between both groups. Meanwhile, there were no significant differences observed in the levels of CAR-T cell expansion and accompanying cytokines release between patients with and without EMDs. CONCLUSIONS: Our study findings have demonstrated the efficacy of CLL1 CAR-T therapy in the treatment of AML patients with EMDs, while also indicating manageable occurrence rates of complications within a tolerable range. The CLL1 CAR-T therapy, serving as an ideal strategy for AML patients irrespective of the presence of EMDs, effectively ameliorates the conditions of AML patients and provides them with an opportunity to undergo curative hematopoietic stem cell transplantation while significantly enhancing their prognosis.

In-Situ Self-respiratory Solid-to-hydrogel Electrolyte Interface Evoked Well-Distributed Deposition on Zinc Anode for Highly Reversible Zinc-ion Batteries.

The aqueous zinc-ion batteries (AZIB) have emerged as a promising technology in the realm of electrochemical energy storage. Despite its potential advantages in terms of safety, cost-effectiveness, and inherent safety, AZIB faces significant challenges. Issues attributed to unsupported thermodynamics and non-uniform potential distribution and deposition, present formidable obstacles that necessitate resolution. To tackle these challenges, a novel strategy adapting hybrid organic-inorganic in-situ derived solid-to-hydrogel electrolyte interface (StHEI) has been developed from coordination reactions and self-respiratory process, establishing uniform diffusion channels by ion bridges and accelerating ion transport. Self-respiratory pattern of StHEI realized through in-situ inorganic component conversion further prolongs the protecting duration, which effectively mitigates corrosion and passivation but enhance the mechanical properties of the StHEI measured through Young's modulus. This novel StHEI promotes well-distributed potential lines within the Helmholtz regions. Zn2+ are finally induced to deposit and nucleate in a compact, fine, and uniform manner. Asymmetrical batteries assembled with the modified Zn electrode and bare Zn exhibit exceptional stability over 3000 h (1 mA cm-2- 0.5 mAh cm-2). The asymmetrical Cu//Zn cell achieved an outstanding average Coulombic efficiency (CE) of 99.6% over 1200 cycles.

Microbial rrn copy number is associated with soil C: N ratio and pH under long-term fertilization.

Soil microbial life-history strategies, as indicated by rRNA operon (rrn) copy numbers, strongly influence agro-ecosystem functioning. Long-term N fertilization causes strong and lasting changes in soil properties, yet its impact on microbial strategies remains largely unexplored. Using long-term field experiments across three agro-ecosystems, we consistently found that N fertilization strongly decreased soil C: N ratio and pH, further increasing the community-level rrn copy number, including both average rrn copy number and total 16S rRNA copy number. Soil C: N stoichiometry balanced by N supplement favored the growth of N-dependent copiotrophic species containing high rrn copy numbers (an average of 2.5) and increased their network connections, predominantly contributing to community-level rrn copy number increase. Decreased soil pH caused by N fertilization also favored the growth of some species whose abundances negatively correlated with pH, partially contributing to the community-level rrn copy number increase. By examining the genomes of two dominant species, we found that microorganisms with a higher rrn copy number (6), e.g., Streptomyces scabiei, possessed more genes related to C and N transport and metabolism. In contrast, the Mycobacterium simiae with a lower rrn copy number (1) has more genes associated with secondary metabolite biosynthesis and lipid transport and metabolism. Our finding challenges the concept of microbial life-strategy regulation solely by nutrient availability, highlighting the important contributions of soil stoichiometric balance and pH to microbial strategies in agro-ecosystems under long-term N inputs.

Case report: Successful combination of CLL1 CAR-T therapy and hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory acute myeloid leukemia.

The incidence of Acute myeloid leukemia (AML) increases with advancing age, and the prognosis for elderly patients is significantly poorer compared to younger patients. Although the combination therapy of venetoclax and hypomethylating agents has demonstrated improved prognosis in patients unable to tolerate intensive chemotherapy, there remains a therapeutic blank for those who fail to achieve remission with current treatment regimens. Here, we report the successful clinical utilization of autogenous CLL1 CAR-T therapy combined with hematopoietic stem cell transplantation in a 73-year-old patient diagnosed with refractory AML. The patient achieved morphological complete remission (CR) with incomplete marrow recovery and a slight presence of minimal residual disease (MRD) after receiving CLL1 CAR-T therapy. To further enhance the treatment and promote the recovery of hemopoiesis, we performed bridged allogenic hematopoietic stem cell transplantation (allo-HSCT) 20 days after the infusion of CLL1 CAR-T cells. The patient achieved MRD-negative CR following HSCT treatment. His primary disease maintained a complete remission status during the 11-month follow-up period. The patient encountered grade 2 cytokine release syndrome and grade 4 granulocytopenia subsequent to the infusion of CAR-T cells, while several rounds of infection and graft-versus-host disease were observed following allo-HSCT. Nevertheless, all these concerns were successfully addressed through comprehensive provision of supportive treatments. We have successfully demonstrated a highly effective and safe combination strategy involving CLL1 CAR-T therapy and allo-HSCT, which has exhibited remarkable tolerability and holds great promise even for elderly patients with AML.

Copper doped carbon dots modified bacterial cellulose with enhanced antibacterial and immune regulatory functions for accelerating wound healing.

The microenvironment of wound healing is susceptible to bacterial infection, chronic inflammation, oxidative stress, and inadequate angiogenesis, requiring the development of innovative wound dressings with antibacterial, anti-inflammatory, antioxidant, and angiogenic capabilities. This research crafted a new multifunctional bacterial cellulose composite membrane infused with copper-doped carbon dots (BC/Cu(II)-RCDs). Findings validated the successful loading of copper-doped carbon dots onto the BC membrane via hydrogen bonding interactions. Compared to the pure BC membrane, the BC/Cu(II)-RCDs composite membrane exhibited significantly enhanced hydrophilicity, tensile properties, and thermal stability. Diverse in vitro assays demonstrated excellent biocompatibility and antibacterial activity of BC/Cu(II)-RCDs composite membranes, alongside their ability to expedite the inflammatory phase and stimulate angiogenesis. In vivo trials corroborated the membrane's ability to foster epithelial regeneration, collagen deposition, and tissue regrowth in full-thickness skin wounds in rats while also curbing inflammation in infected full-thickness skin wounds. More importantly, the treatment of the BC/Cu(II)-RCDs composite membrane may result in the activation of VEGF and MAPK signaling proteins, which are key players in cell migration, angiogenesis, and skin tissue development. In essence, the developed BC/Cu(II)-RCDs composite membrane shows promise for treating infected wounds and serves as a viable alternative material for medicinal bandages.

The presence of spontaneous echo contrast didn't increase the risk for left atrial appendage closure: A propensity score matching analysis based on the CLACBAC study.

Background: Left atrial appendage closure (LAAC) was effective in preventing thromboembolic events and stroke in patients with atrial fibrillation (AF). However, whether left atrial spontaneous echo contrast (LA-SEC) poses a higher risk for thromboembolism is contradictory. We aimed to investigate whether LA-SEC is a risk factor for thromboembolic events in patients who underwent LAAC. Methods: 258 consecutive patients who underwent successful LAAC were enrolled and divided according to the presence or absence of LA-SEC detected by transesophageal echocardiography (TEE). Propensity score matching (PSM) was used to eliminate covariate imbalances. Baseline characteristics, periprocedural details, and clinical outcomes were compared between LA-SEC and non-LA-SEC groups and PSM-matched groups. Results: Of the 258 patients enrolled, mean age was 71.8 ± 8.3 years and 59.3 % were male. LA-SEC group had a higher percentage of persistent AF and worse cardiac function. No significant difference in peri-procedure parameters was found. Through follow-up of 38.1 ± 10.7 months, the total incidence of thromboembolic events and stroke was 7.8 % and 6.6 %, respectively. Though the event-free survival rate of thromboembolic events (Log-Rank P = 0.042) and stroke (Log-Rank P = 0.010) was significantly lower in the LA-SEC group, multivariable COX regression analysis showed LA-SEC was not an independent predictor of thromboembolic events (Hazard ratio 2.073, 95 % Confidence interval 0.845-5.082, P = 0.111). Further survival analysis between PSM-matched groups with comparable baseline characteristics presented no significant difference in survival free from thromboembolic events (Log-Rank P = 0.616) and stroke (Log-Rank P = 0.312). Conclusion: Patients with LA-SEC had worse condition, while LA-SEC per se did not increase the incidence of thromboembolic events and stroke for patients who underwent LAAC.

A multi-verse optimizer-based CNN-BiLSTM pixel-level detection model for peanut aflatoxins.

Peanuts are highly susceptible to contamination by aflatoxins, posing a significant threat to human health. This study aims to enhance the accuracy of pixel-level aflatoxin detection in hyperspectral images using an optimized deep learning method. This study developed a CNN-BiLSTM fusion model optimized by the Multi-Verse Optimizer (MVO) algorithm, specifically designed to detect aflatoxins with high precision. The optimized CNN-BiLSTM model was fine-tuned using aflatoxin spectral data at varying concentrations. The results indicate that the fine-tuned MVO-CNN-BiLSTM model achieved the best performance, with a validation accuracy of 94.92 % and a recall rate of 95.59 %. The accuracy of this model is 6.93 % and 3.6 % higher than machine learning methods such as SVM and AdaBoost, respectively. Additionally, it is 4.18 % and 3.08 % higher than deep learning methods such as CNN and the CNN-LSTM fusion model, respectively. This method enhances pixel-level aflatoxin detection accuracy, supporting the development of online detection devices.

Molecular and spatial signatures of human and rat corpus cavernosum physiopathological processes at single-cell resolution.

The composition and cellular heterogeneity of the corpus cavernosum (CC) microenvironment have been characterized, but the spatial heterogeneity at the molecular level remains unexplored. In this study, we integrate single-cell RNA sequencing (scRNA-seq) and spatial transcriptome sequencing to comprehensively chart the spatial cellular landscape of the human and rat CC under normal and disease conditions. We observe differences in the proportions of cell subtypes and marker genes between humans and rats. Based on the analysis of the fibroblast (FB) niche, we also find that the enrichment scores of mechanical force signaling vary across different regions and correlate with the spatial distribution of FB subtypes. In vitro, the soft and hard extracellular matrix (ECM) induces the differentiation of FBs into apolipoprotein (APO)+ FBs and cartilage oligomeric matrix protein (COMP)+ FBs, respectively. In summary, our study provides a cross-species and physiopathological transcriptomic atlas of the CC, contributing to a further understanding of the molecular anatomy and regulation of penile erection.

Heterologous expression of the Oenococcus oeni two-component signal transduction response regulator in the Lactiplantibacillus plantarum WCFS1 strain enhances acid stress tolerance.

BACKGROUND: Oenococcus oeni is a commercial wine-fermenting bacterial strain, owing to its high efficiency of malolactic fermentation and stress tolerance. The present study explored the function of key genes in O. oeni to enhance stress resistance by heterologous expression of these genes in another species. RESULTS: The orf00404 gene that encodes a two-component signal transduction response regulator in O. oeni was heterologously expressed in Lactiplantibacillus plantarum WCFS1. The expression of orf00404 significantly enhanced the growth rate of the recombinant strain under acid stress. At 60 h, 72 h, and 108 h of culture at pH 4.0, the recombinant strain had 1562, 641, and 748 differentially expressed genes compared to the control strain, respectively. At all three time points, 20 genes were upregulated in the recombinant strain, including the lamA-D operon-coding genes of the quorum-sensing two component signal transduction system and the spx5 RNA polymerase-binding protein coding gene, which may help adaptation to acid stress. In addition, 47 genes were downregulated in the recombinant strain at all three time points, including the hsp1 heat shock protein-coding gene, the trxA1 thioredoxin-coding gene, and the dinP, mutY, umuC, and uvrB DNA damage repair-related protein-coding genes, potentially indicating that the recombinant strain was less susceptible to stress and had less DNA damage than the control strain in acid stress conditions. The recombinant strain had higher membrane fluidity, permeability, and integrity at an early stage of logarithmic growth (72 h), suggesting that it had a more complete and active cell membrane state at this stage. The intracellular ATP content was significantly reduced in the recombinant strain at the beginning of logarithmic growth (60 h), implying that the recombinant strain consumed more energy at this stage to resist acid stress and growth. CONCLUSIONS: These results indicated that the recombinant strain enhances acid stress tolerance by regulating a gene expression pattern, increasing ATP consumption, and enhancing cell membrane fluidity, membrane permeability, and membrane integrity at specific growth stages. Thus, the recombinant strain may have potential application in the microbial biotechnology industry.

A Novel 5-Chloro-N-Phenyl-1 H-Indole-2-carboxamide Derivative as a Glycogen Phosphorylase Inhibitor: Evaluating the Long-Term Drug Effects on Muscle Function for the First Time.

Compound 1 was previously identified by our team as a glycogen phosphorylase (GP) inhibitor with glucose-lowering activity and demonstrated to have protective effects against myocardial and cerebral ischemia. However, its impact on muscle function has not been clarified. This study is the first to evaluate the long-term effects of GP inhibitors on muscle function and metabolism. After a 28-day administration of Compound 1, we performed assays to assess muscle function and biochemical parameters in rats. We observed reductions in peak holding force, duration, tetanic contraction force, single-contraction force, and electromyographic signals under 20 s and 10 min contraction stimuli. The metabolic analysis showed no significant effects on muscle glycogen, ATP, lactic acid, and uric acid levels at low doses. In contrast, medium to high doses resulted in increased glycogen, decreased ATP, and reduced lactic acid (only at high doses), without affecting uric acid. These findings suggest that Compound 1 may adversely affect muscle function in rats, potentially due to the glycogen inhibition effects of GP inhibitors. This study provides crucial safety data and insights into the long-term effects of GP inhibitors on rat muscles, which will guide future developments and applications.

A recent perspective on designing tumor vaccines for tumor immunology.

With the rapid development of immunotherapy, therapeutic tumor vaccines, which aim to enhance the immunogenicity of tumor cells and activate the patient's immune system to kill tumor cells, as well as eliminate or inhibit tumor growth, have drawn increasing attention in the field of tumor therapy. However, due to the lack of immune cell infiltration, low immunogenicity, immune escape and other problems, the efficacy of tumor vaccine is often limited. Researchers have developed a variety of strategies to enhance tumor immune recognition, such as improving the immunogenicity of tumor antigens, selecting a suitable vaccine platform, or combining tumor vaccines with other anticancer treatments. In this review, we will deliberate on how to overcome the problem of therapeutic tumor vaccines, and discuss the up-to-date progress and achievements in the tumor vaccine development, as well as their future in cancer treatment.

Quasi-equilibrium growth of inch-scale single-crystal monolayer α-In2Se3 on fluor-phlogopite.

Epitaxial growth of two-dimensional (2D) materials with uniform orientation has been previously realized by introducing a small binding energy difference between the two locally most stable orientations. However, this small energy difference can be easily disturbed by uncontrollable dynamics during the growth process, limiting its practical applications. Herein, we propose a quasi-equilibrium growth (QEG) strategy to synthesize inch-scale monolayer α-In2Se3 single crystals, a semiconductor with ferroelectric properties, on fluor-phlogopite substrates. The QEG facilitates the discrimination of small differences in binding energy between the two locally most stable orientations, realizing robust single-orientation epitaxy within a broad growth window. Thus, single-crystal α-In2Se3 film can be epitaxially grown on fluor-phlogopite, the cleavage surface atomic layer of which has the same 3-fold rotational symmetry with α-In2Se3. The resulting crystalline quality enables high electron mobility up to 117.2 cm2 V-1 s-1 in α-In2Se3 ferroelectric field-effect transistors, exhibiting reliable nonvolatile memory performance with long retention time and robust cycling endurance. In brief, the developed QEG method provides a route for preparing larger-area single-crystal 2D materials and a promising opportunity for applications of 2D ferroelectric devices and nanoelectronics.

Whatever does not kill them makes them stronger: Using quaternary ammonia antimicrobials to alleviate the inhibition of ammonia oxidation under perfluorooctanoic acid stress.

Perfluorooctanoic acid (PFOA), benzalkyl dimethylammonium compounds (BAC) and antibiotic resistance genes (ARGs) have negative effects on biological sewage treatment. The performance of nitrification systems under stress of PFOA (0.1-5 mg/L) or/and BAC (0.2-10 mg/L) was explored during 84-day experiments using four sequencing batch reactors, in this study. Low (0.1 mg/L) concentration PFOA had a positive influence on ammonia removal, while medium and high (2 and 5 mg/L) concentrations PFOA caused severe inhibition. Meanwhile, PFOA stress resulted in the enrichment of ARGs in water (w-ARGs). BAC (0-10 mg/L) had no obvious influence on ammonia removal. However, BAC promoted the reduction of ARGs and the bacterial community was the main participator (48.07%) for the spread of ARGs. Interestingly, the joint stress of PFOA and BAC increased the ammonia-oxidizing bacteria (AOB) activity from 5.81 ± 0.19 and 6.05 ± 0.79 mg N/(g MLSS·h) to 7.09 ± 0.87 and 7.23 ± 0.29 mg N/(g MLSS·h) in medium and high concentrations, compared to single stress of PFOA, which was observed for the first time. BAC could reduce bioavailability of PFOA through competitive adsorption and decreasing sludge hydrophobicity by the lower ß-Sheet and α-Helix in tightly bound protein. Furthermore, the joint stress of PFOA and BAC was able to intensify the proliferation of w-ARGs and extracellular ARGs in sludge, and developed the most active horizontal gene transfer mediated by intl1 compared to single stress of PFOA or BAC. The batch tests verified the detoxification capacity of BAC on nitrification under 2.5 mg/L PFOA (48 h exposing), and the maximum alleviation of AOB activity was achieved at BAC and PFOA mass ratio of 2:1. In summary, BAC could be used to alleviate the inhibition of PFOA on ammonia oxidation, providing an efficient and sustainable approach in wastewater treatment.

Engineered Carrier-Free Nanosystem-Induced In Situ Therapeutic Vaccines for Potent Cancer Immunotherapy.

In situ vaccines that can stimulate tumor immune response have emerged as a breakthrough in antitumor therapy. However, the immunosuppressed tumor microenvironment and insufficient infiltration of immune cells lead to ineffective antitumor immunity. Hence, a biomimetic carrier-free nanosystem (BCC) to induce synergistic phototherapy/chemotherapy-driven in situ vaccines was designed. A carrier-free nanosystem was developed using phototherapeutic reagents CyI and celastrol as raw materials. In vitro and in vivo studies have shown that under NIR light irradiation, BCC-mediated photo/chemotherapy not only accelerates the release of drugs to deeper parts of tumors, achieving timing and light-controlled drug delivery to result in cell apoptosis, but also effectively stimulates the antitumor response to induce in situ vaccine, which could invoke long-lasting antitumor immunity to inhibit tumor metastasis and eliminate distant tumor. This therapeutic strategy holds promise for priming robust innate and adaptive immune responses, arresting cancer progression, and inducing tumor dormancy.

Derivation of Dental Epithelial-like Cells from Murine Embryonic Stem Cells for Tooth Regeneration.

Teeth are comprised of epithelial and mesenchymal cells, and regenerative teeth rely on the regeneration of both cell types. Transcription factors play a pivotal role in cell fate determination. In this study, we establish fluorescence models based on transcription factors to monitor and analyze dental epithelial cells. Using Pitx2-P2A-copGFP mice, we observe that Pitx2+ epithelial cells, when combined with E14.5 dental mesenchymal cells, are sufficient for the reconstitution of teeth. Induced-Pitx2+ cells, directly isolated from the embryoid body that employs the Pitx2-GFP embryonic stem cell line, exhibit the capacity to differentiate into ameloblasts and develop into teeth when combined with dental mesenchymal cells. The regenerated teeth exhibit a complete structure, including dental pulp, dentin, enamel, and periodontal ligaments. Subsequent exploration via RNA-seq reveals that induced-Pitx2+ cells exhibit enrichment in genes associated with FGF receptors and WNT ligands compared with induced-Pitx2- cells. Our results indicate that both primary Pitx2+ and induced Pitx2+ cells possess the capability to differentiate into enamel-secreting ameloblasts and grow into teeth when combined with dental mesenchymal cells.

Continuous Flow Microreactors for the High-efficiency Enzymatic Synthesis of 10-Hydroxystearic Acid from Oleic Acid.

Converting fatty acids into specialty chemicals is sustainable but hindered by the low efficiency and thermal instability of current oleic acid hydratases, along with mass transfer limitations in emulsion reactions. This study introduces an optimized continuous flow micro-reactor (CFMR) that efficiently transforms oleic acid at low (15 g·L-1) and high (50 g·L-1) concentrations, improving reaction efficiency and overcoming key conversion barriers. The first CFMR model showed reaction speeds surpassing traditional batch stirred tank reactors (BSTR). Optimizations were performed on three key components: liquid storage, mixer, and reaction section of the CFMR, with each round's best conditions carried into the next. This achieved a space-time yield of 597 g·L-1·d-1 at a 15 g·L-1 oleic acid load. To further enhance the yield, we optimized the emulsifier system to solve incomplete emulsification and developed a two-component feed microreactor (TCFMR) that addressed substrate and product inhibition at high loads, reaching a 91% conversion of 50 g·L-1 oleic acid in 30 minutes, with a space-time yield of 2312 g·L-1·d-1. These advancements represent significant progress in utilizing fatty acids and advancing sustainable chemical synthesis.

Bioactivity and in vitro immunological studies of xenogeneic decellularized extracellular matrix scaffolds for implantable applications.

Decellularized scaffolds retain the main bioactive substances of the extracellular matrix, which can better promote cell proliferation and matrix reconstruction at the defect site, and have great potential for morphological and functional restoration in patients with tissue defects. Due to the safety of the material source of allogeneic decellularized scaffolds, there is a great limitation in their clinical application, so the preparation and evaluation of xenodermal acellular scaffolds have attracted much attention. In terms of skin tissue structure and function, porcine skin has a high degree of similarity to human skin and has the advantages of sufficient quantity and no ethical issues. However, there is a risk of immune rejection after xenodermal acellular scaffold transplantation. To address the above problems, this paper focuses on porcine dermal decellularized scaffolds prepared using two common decellularization preparation methods and compares the decellularization efficiency, retention of active components of the extracellular matrix, structural characterization of the decellularized scaffolds, and the effect of porcine dermal decellularized scaffolds on mouse Raw264.7 macrophages, so as to make a functional evaluation of the active components and immune effects of porcine dermal decellularized scaffolds, and to provide a reference for filling trauma-induced defects in humans.

Key Genes FECH and ALAS2 under Acute High-Altitude Exposure: A Gene Expression and Network Analysis Based on Expression Profile Data.

High-altitude acclimatization refers to the physiological adjustments and adaptation processes by which the human body gradually adapts to the hypoxic conditions of high altitudes after entering such environments. This study analyzed three mRNA expression profile datasets from the GEO database, focusing on 93 healthy residents from low altitudes (≤1400 m). Peripheral blood samples were collected for analysis on the third day after these individuals rapidly ascended to higher altitudes (3000-5300 m). The analysis identified significant differential expression in 382 genes, with 361 genes upregulated and 21 downregulated. Further, gene ontology (GO) annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis indicated that the top-ranked enriched pathways are upregulated, involving blood gas transport, erythrocyte development and differentiation, and heme biosynthetic process. Network analysis highlighted ten key genes, namely, SLC4A1, FECH, EPB42, SNCA, GATA1, KLF1, GYPB, ALAS2, DMTN, and GYPA. Analysis revealed that two of these key genes, FECH and ALAS2, play a critical role in the heme biosynthetic process, which is pivotal in the development and maturation of red blood cells. These findings provide new insights into the key gene mechanisms of high-altitude acclimatization and identify potential biomarkers and targets for personalized acclimatization strategies.

Effects of Substituting Tenebrio molitor and Elodea nuttallii as Feed on Growth, Flesh Quality and Intestinal Microbiota of Red Swamp Crayfish (Procambarus clarkii).

This study aimed to evaluate the impact of substituting a portion of feed with Tenebrio molitor (TM) and Elodea nuttallii (EN) on crayfish culture. A total of 270 crayfish (5.1 ± 0.4 g) were fed three different diet combinations (A: 100% feed; B: 80% feed + 10% TM + 10% EN; C: 75% feed + 15% TM + 10% EN) for 12 weeks. The findings demonstrated that group C had an important beneficial impact on the growth performance of crayfish. This was evidenced by a rise in digestive enzyme activity (trypsin, lipase, and cellulase) in the intestinal and hepatopancreas, as well as an upregulation in the expression of growth-related genes (ghsr, igfbp7, mhc, mlc1, mef2, and pax7) in the muscle. Furthermore, the assessment of the flesh quality of crayfish muscle in group C was conducted. The findings indicated a significant increase (p < 0.05) in the energy value (moisture, crude protein, and crude lipid) within the muscle. The levels of delicious amino acids (Glu, Ala, Ser, Gly, and Tyr) and polyunsaturated fatty acids (ARA, DHA) were enhanced, resulting in an improved nutritional profile and flavor of the muscle while maintaining the Σn-3/Σn-6 ratio. The remodeling of the intestinal microbiota (abundance of Proteobacteria and ratio of Firmicutes/Bacteroidota bacteria) also revealed improved growth performance. Additional research is necessary to ascertain whether excessive use of TM or EN feed substitution can have negative effects on crayfish culture.

Preparation and Properties of Composite Double-Network Gel for Inhibiting Coal Spontaneous Combustion.

In order to improve the inhibition effect of gel on coal spontaneous combustion, a chitosan (CS)/polyacrylamide (PAM)/metal ion (Al3+) composite double-network gel was developed in this study. The optimum formula of the composite double-network gel was determined using orthogonal experimentation. The microstructure, water retention, compressibility, and anti-destruction properties of the composite double-network gel were analyzed. The inhibition effect of the composite double-network gel on coal spontaneous combustion was studied via infrared spectroscopy and a synchronous thermal analyzer from the micro and macro perspectives. The results show that the composite double-network gel has a denser interpenetrating double-network structure and a larger void ratio than the ordinary gel. The water retention rate was 55% after standing at 150 °C for 12 h. The deformation memory ratio of the composite double-network gel was 78%, which was 26.8% higher than that of the ordinary gel, and the compressive strength also increased by 59.96%. In addition, the critical temperature point and the maximum thermal weight-loss rate temperature point decreased by 7.01 °C and 39.62 °C, respectively, and the composite double-network gel effectively reduced active functional groups in the treated coal sample, such as hydroxyl and aliphatic hydrocarbons. In this study, a CS/PAM/Al3+ composite double-network gel was produced, which exhibited good gel performance and inhibition effects, with physical effects such as the covering, wetting, and cementation of coal.