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Acid mine drainage(AMD) from coal mines contains elevated concentrations of heavy metals and sulfates, rendering it highly corrosive and posing a persistent threat to both the ecological environment and human health. Consequently, it has emerged as a pervasive environmental predicament in the coal mining process. This review presents an overview of the formation mechanism, detrimental effects, and chemical characteristics of AMD in coal mines. Furthermore, it summarizes traditional AMD end treatment methods in recent years, analyzes and compares practical application cases of AMD end treatment in China, and introduces emerging AMD end treatment methods. The reaction mechanisms, advantages, disadvantages of traditional active treatments (neutralization, adsorption, membrane technology), as well as passive treatments (constructed wetlands, limestone ditch drainage), are discussed extensively. Moreover, the applicability of each treatment method is evaluated. However, these methods still have certain limitations. The active method is constrained by the continuous supply of chemicals and energy as well as high maintenance costs. On the other hand, the passive approach is limited by long treatment cycles and the need for timely system renovation. According to the actual application cases, the treatment ideas and optimization methods of domestic AMD end treatment methods are summarized. In order to address these challenges in acid mine drainage treatment within coal mines, this review introduces magnetic nanoparticle materials and a novel collaborative treatment method, providing a fresh perspective. The findings of this study highlight the ongoing necessity to enhance existing technologies and develop new ones to improve the overall effectiveness of acid mine drainage treatment. Relying solely on a single technology proves difficult in meeting discharge standards for acid mine drainage treatment; therefore, adopting a multi-technology collaborative approach based on complementary advantages becomes imperative. Furthermore, during the process of AMD treatment，the approach of “source reduction + end treatment” can be adopted to improve the effectiveness of AMD treatment, resource recovery and reuse can help reduce treatment costs while promoting sustainable management.

Abstract Meiosis in males is a critical process that ensures complete spermatogenesis and genetic diversity. However, the key regulators involved in this process and the underlying molecular mechanisms remain unclear. Here, we report an essential role of the m6A methyltransferase METTL16 in meiotic sex chromosome inactivation (MSCI), double‐strand break (DSB) formation, homologous recombination and SYCP1 deposition during male meiosis. METTL16 depletion results in a significantly upregulated transcriptome on sex chromosomes in pachytene spermatocytes and leads to reduced DSB formation and recombination, and increased SYCP1 depositioin during the first wave of spermatogenesis. Mechanistically, in pachytene spermatocytes, METTL16 interacts with MDC1/SCML2 to coordinate DNA damage response (DDR) and XY body epigenetic modifications that establish and maintain MSCI, and in early meiotic prophase I, METTL16 regulates DSB formation and recombination by regulating protein levels of meiosis‐related genes. Furthermore, multi‐omics analyses reveal that METTL16 interacts with translational factors and controls m6A levels in the RNAs of meiosis‐related genes (e.g., Ubr2) to regulate the expression of critical meiotic regulators. Collectively, this study identified METTL16 as a key regulator of male meiosis and demonstrated that it modulates meiosis by interacting with MSCI‐related factors and regulating m6A levels and translational efficiency (TE) of meiosis‐related genes.

Abstract Background The mitosis-to-meiosis switch during spermatogenesis requires dynamic changes in gene expression. However, the regulation of meiotic transcriptional and post-transcriptional machinery during this transition remains elusive. Results We report that methyltransferase-like protein 16 (METTL16), an N6-methyladenosine (m6A) writer, is required for mitosis-to-meiosis transition during spermatogenesis. Germline conditional knockout of Mettl16 in male mice impairs spermatogonial differentiation and meiosis initiation. Mechanistically, METTL16 interacts with splicing factors to regulate the alternative splicing of meiosis-related genes such as Stag3. Ribosome profiling reveals that the translation efficiency of many meiotic genes is dysregulated in METTL16-deficient testes. m6A-sequencing shows that ablation of METTL16 causes upregulation of the m6A-enriched transcripts and downregulation of the m6A-depleted transcripts, similar to Meioc and/or Ythdc2 mutants. Further in vivo and in vitro experiments demonstrate that the methyltransferase activity site (PP185-186AA) of METTL16 is necessary for spermatogenesis. Conclusions Our findings support a molecular model wherein the m6A writer METTL16-mediated alternative splicing and translation efficiency regulation are required to control the mitosis-to-meiosis germ cell fate decision in mice, with implications for understanding meiosis-related male fertility disorders.

Auricularia heimuer is a valuable traditional Chinese fungus used as food and medicine. Hei29 is a strain derived from wild A. heimuer through systematic domestication and selection. It has been the primary A. heimuer variety in Northeast China for 30 years and offers the advantages of high yield, good commercial property, and stable traits. This study used protoplast nucleation on Hei29 to produce two amiable and paired monokaryons, Hei29-D1 and Hei29-D2. The genome of Hei29 was sequenced utilizing the Illumina PE150 and PacBio Sequel sequencing platforms. Hei29-D1 and Hei29-D2 had genomic sizes of 47.54 Mb and 47.49 Mb, GC contents of 56.95% and 56.99%, and an N50 of 2.37 Mb and 4.28 Mb, respectively. Hei29’s genome possessed two phytoene synthase (PSY) protein genes, one of which—PSY encoded by g894—has a transmembrane domain. The phylogenetic tree showed that Hei29 shared the closest evolutionary relationship with Auricularia subglabra TFB-10046 SS5. Collinearity analysis showed that the correlation between the two monokaryons was as high as 90.81%. Cluster analysis revealed that Hei29 contains 12,362 core genes, 223 unique genes in Hei29-D1, and 228 unique genes in Hei29-D2. This study is the first to sequence two related and paired monokaryons from A. heimuer, which is critical for fully understanding the genetic composition and information of the characteristic strain of A. heimuer in Northeast China. It establishes the data and theoretical foundation for gene mining, usage, and molecular breeding. It further promotes the genetic breeding and active substance utilization of A. heimuer.

Dysregulation of histone deacetylases (HDACs) is closely related to tumor development and progression. As promising anticancer targets, HDACs have gained a great deal of research interests and two decades of effort has led to the approval of five HDAC inhibitors (HDACis). However, currently traditional HDACis, although effective in approved indications, exhibit severe off-target toxicities and low sensitivities against solid tumors, which have urged the development of next-generation of HDACi. This review investigates the biological functions of HDACs, the roles of HDACs in oncogenesis, the structural features of different HDAC isoforms, isoform-selective inhibitors, combination therapies, multitarget agents and HDAC PROTACs. We hope these data could inspire readers with new ideas to develop novel HDACi with good isoform selectivity, efficient anticancer effect, attenuated adverse effect and reduced drug resistance.

Summary: Although the composition and assembly of stress granules (SGs) are well understood, the molecular mechanisms underlying SG disassembly remain unclear. Here, we identify that heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) is associated with SGs and that its absence specifically enhances the disassembly of arsenite-induced SGs depending on the ubiquitination-proteasome system but not the autophagy pathway. hnRNPA2B1 interacts with many core SG proteins, including G3BP1, G3BP2, USP10, and Caprin-1; USP10 can deubiquitinate G3BP1; and hnRNPA2B1 depletion attenuates the G3BP1-USP10/Caprin-1 interaction but elevates the G3BP1 ubiquitination level under arsenite treatment. Moreover, the disease-causing mutation FUSR521C also disassembles faster from SGs in HNRNPA2B1 mutant cells. Furthermore, knockout of hnRNPA2B1 in mice leads to Sertoli cell-only syndrome (SCOS), causing complete male infertility. Consistent with this, arsenite-induced SGs disassemble faster in Hnrnpa2b1 knockout (KO) mouse Sertoli cells as well. These findings reveal the essential roles of hnRNPA2B1 in regulating SG disassembly and male mouse fertility.

Rehmannia glutinosa is one of the most important medicinal plants in China and is affected by viral diseases. In this study, a new virus tentatively named Rehmannia Allexivirus virus (ReAV) was identified through high-throughput sequencing, reverse-transcription polymerase chain reaction (RT-PCR), and Sanger sequencing. The complete genome length was 7297 nt and it contained five open reading frames (ORFs) encoding replicase, triple gene block 1(TGB1), TGB2, TGB3, and coat protein (CP). The replicase and CP presented nucleotide homology ranges of 59.9–65.2% and 47.5–55.5% between the nine ReAV isolates and the other 12 species of the genus Allexivirus. In the nine isolates, ReAV-20 and ReAV-31 isolates showed breakpoints in the replicase and CP regions, respectively. The other isolates shared 87.2–96.5% nt with the whole genome nucleotide identity. The phylogenetic tree showed that seven ReAV isolates based on replicase, CP, and whole genome sequences were clustered in the same branch and were related to the genus Allexivirus. The ReAV detection rates for 60 R. glutinosa samples were 73.3–81.7% through RT-PCR using primers targeting the replicase or CP genes. These results demonstrate that ReAV is the dominant virus in R. glutinosa. This study provides important evidence for understanding viruses infecting R. glutinosa and for establishing efficient strategies to prevent viral spread.

Cooking is a way of processing food materials to make food more delicious, better-looking and better-smelling. It not only makes people feel satisfied when eating, but also makes food nutrients more easily absorbed by the body. As a common edible ingredient, vegetables are indispensable whether in the home or restaurant. Vegetables are heated during the cooking process, so the nutrient composition and the color are changed. Compared with other cooking methods, steaming is a relatively healthy cooking method, which could retain more nutrients. In this paper, the effects of several cooking methods, such as steaming, boiling, microwaving, and stir-frying on various nutrients, antioxidant capacity and color in vegetables are investigated, in order to selectively provide reference for consumers to choose cooking methods.

BackgroundSea-level residents experience altitude sickness when they hike or visit altitudes above ~2,500 m due to the hypobaric hypoxia (HH) conditions at such places. HH has been shown to drive cardiac inflammation in both ventricles by inducing maladaptive metabolic reprogramming of macrophages, which evokes aggravated proinflammatory responses, promoting myocarditis, fibrotic remodeling, arrhythmias, heart failure, and sudden deaths. The use of salidroside or altitude preconditioning (AP) before visiting high altitudes has been extensively shown to exert cardioprotective effects. Even so, both therapeutic interventions have geographical limitations and/or are inaccessible/unavailable to the majority of the population as drawbacks. Meanwhile, occlusion preconditioning (OP) has been extensively demonstrated to prevent hypoxia-induced cardiomyocyte damage by triggering endogenous cardioprotective cascades to mitigate myocardial damage. Herein, with the notion that OP can be conveniently applied anywhere, we sought to explore it as an alternative therapeutic intervention for preventing HH-induced myocarditis, remodeling, and arrhythmias.MethodsOP intervention (6 cycles of 5 min occlusion with 200 mmHg for 5 min and 5 min reperfusion at 0 mmHg – applying to alternate hindlimb daily for 7 consecutive days) was performed, and its impact on cardiac electric activity, immunoregulation, myocardial remodeling, metabolic homeostasis, oxidative stress responses, and behavioral outcomes were assessed before and after exposure to HH in mice. In humans, before and after the application of OP intervention (6 cycles of 5 min occlusion with 130% of systolic pressure and 5 min reperfusion at 0 mmHg – applying to alternate upper limb daily for 6 consecutive days), all subjects were assessed by cardiopulmonary exercise testing (CPET).ResultsComparing the outcomes of OP to AP intervention, we observed that similar to the latter, OP preserved cardiac electric activity, mitigated maladaptive myocardial remodeling, induced adaptive immunomodulation and metabolic homeostasis in the heart, enhanced antioxidant defenses, and conferred resistance against HH-induce anxiety-related behavior. Additionally, OP enhanced respiratory and oxygen-carrying capacity, metabolic homeostasis, and endurance in humans.ConclusionsOverall, these findings demonstrate that OP is a potent alternative therapeutic intervention for preventing hypoxia-induced myocarditis, cardiac remodeling, arrhythmias, and cardiometabolic disorders and could potentially ameliorate the progression of other inflammatory, metabolic, and oxidative stress-related diseases.

Stress granules (SGs) are membraneless cytoplasmic condensates that dynamically assemble in response to various stressors and reversibly disassemble after stimulus removal; however, the mechanisms underlying SG dynamics and their physiological roles in germ cell development are elusive. Here, we show that SERBP1 (SERPINE1 mRNA binding protein 1) is a universal SG component and conserved regulator of SG clearance in somatic and male germ cells. SERBP1 interacts with the SG core component G3BP1 and 26S proteasome proteins PSMD10 and PSMA3 and recruits them to SGs. In the absence of SERBP1, reduced 20S proteasome activity, mislocalized valosin containing protein (VCP) and Fas associated factor family member 2 (FAF2), and diminished K63-linked polyubiquitination of G3BP1 during the SG recovery period were observed. Interestingly, the depletion of SERBP1 in testicular cells in vivo causes increased germ cell apoptosis upon scrotal heat stress. Accordingly, we propose that a SERBP1-mediated mechanism regulates 26S proteasome activity and G3BP1 ubiquitination to facilitate SG clearance in both somatic and germ cell lines.

Abstract Ferroptosis is a newly characterized form of non-apoptotic-programmed cell death, which is driven by the lethal accumulation of iron-catalyzed lipid peroxides. Uncontrolled ferroptosis is implicated in the pathogenesis of a group of human diseases, while targeted induction of ferroptosis provides a potent therapeutic design for cancers. During the past decade, the fundamental regulatory circuits of ferroptosis have been identified. In this study, we show that the multifaceted Ser/Thr protein kinase GSK-3β acts as a positive modulator of the ferroptosis program. Pharmacological inhibition of GSK-3β by selective inhibitor LY2090314 or genetic KD of GSK-3β by shRNA potently promotes ferroptotic resistance. GSK-3β KD antagonizes the expression of iron metabolic components including DMT1, FTH1, and FTL, leading to the disruption of iron homeostasis and decline in intracellular labile free iron level. Taken together, our findings elaborate an indispensable role of GSK-3β in determining ferroptotic sensitivity by dominating cellular iron metabolism, which provides further insight into GSK-3β as a target for cancer chemotherapy.

Particulate matter 2.5 (PM2.5) has adverse biological effects on major living organs in the body, including lungs. The complex composition of PM2.5, including carbon black and heavy metals, cause toxic effects to the lung. Nonetheless, there exists considerable knowledge gaps regarding the impact of carbon black (CB) on environmental health and safety (EHS). Thus far, the synergistic effects of CB have not gained much attention in past decades. Here, we showed that combined exposure of CB and Cadmium (Cd) enhance the cytotoxicity by altering the state of cell membrane. Specially, CB caused cell membrane collapse and increased the permeability of cells, and remarkedly enhanced the metal Cd toxicity. Furthermore, upon pre-treatment sublethal-dose CB, the increased intracellular Cd brought about a significantly amount of lactate dehydrogenase (LDH) and high expression of metallothionein-1 (MT-1) in human lung epithelial cell line (BEAS-2B) cells, and ultimately resulted an increased cellular toxicity. The lung of mice exposed CBs and Cd presented remarkably inflammation than Cd alone. Mechanistic exploration deciphered that CB pre-treatment triggered cell damage via apoptosis due to Cd exposure. Collectively, our findings reveal a novel path for understanding the impact of CB on EHS with its synergistic effects, through which nanomaterials might exert detrimental effects on organisms.

Aiming to improve the road friendliness so as to reduce the road damage caused by heavy multi-axle vehicles, and to enhance the ride comfort, we propose a kind of hydro-pneumatic ISD suspension structure, which is equivalent to a two-stage ISD structure integrating a traditional hydro-pneumatic suspension and a fluid inerter. Firstly, based on the 1/4 model, a genetic algorithm is used to optimize the key structural parameters of hydro-pneumatic ISD suspension. Secondly, the AMESim dynamic model of heavy multi-axle vehicles is built for the performance comparison between the traditional hydraulic and hydro-pneumatic ISD suspensions. Finally, this paper machines a hydro-pneumatic ISD suspension to replace the traditional hydraulic one in a heavy multi-axle vehicle to carry out a road test. Test results indicate that the proposed suspension can effectively restrain the vibrations of sprung and unsprung mass and improve ride comfort as well as road friendliness. The hydro-pneumatic ISD suspension can be applied to engineering.

The aim of the present study was to examine the neuroprotective effect of Qingnao dripping pills (QNDP), especially the infiltration of neutrophils and macrophages, as well as the mitogen-activated protein kinase (MAPK) signal pathway. Adult male Sprague–Dawley rats were randomized to three groups: sham, MCAO, and QNDP. After 24 h of ischemia and reperfusion, neurological deficit scores and infarct volume were measured. Macrophages and neutrophil infiltration in the ischemic brain were respectively determined with CD68 and MPO immunofluorescence and western blot. The proteins involved in MAPK signaling (SAPK/JNK, P-SAPK/JNK, p38, P-p38, ERK1/2, and P-ERK1/2) were measured by western blotting. In vitro ischemic paradigm (oxygen-glucose deprivation) was performed in SH-SY5Y cells to evaluate the effects of QNDP. The viability and death ration of cells induced OGD/R was measured by MTT and LDH assay. The proteins involved in MAPK signaling were measured by western blotting. The results showed that QNDP treatment significantly improved the neurological deficit scores and reduced infarct size. In addition, QNDP treatment inhibited the number of CD68- and MPO-positive cells in the ischemic brain. It inhibited the MAPK signaling pathway in the ischemic brain and SH- SY5Y cells induced OGD/R. Keywords: Acute ischemic stroke, QNDP, Immune-inflammatory response, MAPK signaling pathway, MCAO

Glycogen storage disease (GSD) Ib is a rare genetic metabolic disorder caused by gene mutation in the glucose 6-phosphate transport gene SLC37A4 (OMIM# 602671). This study aimed to explore the association between a novel lipoprotein lipase (LPL) mutation and severe hypertriglyceridemia in a GSD Ib infant with severe hypertriglyceridemia. A 5-month-old girl was admitted to our hospital because of repeated episodes of low-grade fever over the past month and because of neutropenia. The patient was diagnosed with GSD Ib and severe hypertriglyceridemia based on clinical manifestations and laboratory test results. Next-generation sequencing and Sanger sequencing were then applied to DNA from the peripheral blood of the patient and her parents to analyze gene mutations. Pathogenicity prediction analysis was performed using Sorting Intolerant From Tolerant (SIFT) and PolyPhen-2 platforms. The results revealed that this infant carried a compound heterozygous variation in the SLC37A4 gene, a c.1043T > C (p.L348P) mutation derived from her mother and a c.572C > T (p.P191L) mutation derived from her father. In addition, a novel c.483delA (p. A162Pfs*10) frameshift mutation was found in the patient's LPL gene exon 4, which was derived from the heterozygous carrier of her father. The SIFT and PolyPhen-2 prediction programs indicated that these mutations were likely harmful. Medium-chain triglyceride milk and granulocyte colony-stimulating factor subcutaneous injection alleviated the symptoms. Our findings identified a novel LPL gene frameshift mutation combined with SLC37A4 gene compound heterozygous mutations in a GSD Ib infant with severe hypertriglyceridemia.

Reproduction is an energy demanding function and only take place in case of sufficient available energy status in mammals. Metabolic diseases such as anorexia nervosa are clinically associated with reduced fertility. AMP-activated protein kinase (AMPK), as a major regulator of cellular energy homeostasis, is activated in limited energy reserves to ensure the orderly progress of various physiological activities. In recent years, mounting evidence shows that AMPK is involved in the regulation of reproductive function through multiple mechanisms. AMPK is likely to be a metabolic sensor integrating central and peripheral signals. In this review, we aim to explore the preclinical studies published in the last decade that investigate the role of AMP-activated protein kinase in the reproductive field, and its role as a target for drug therapy of reproductive system-related diseases. We also emphasized the emerging roles of AMPK in transcriptional regulation of reproduction processes and metabolisms, which are tightly related to the energy state and fertility of an organism.

Ischemic stroke patients suffer from relatively limited treatment options. Studies have shown that in cerebral ischemia, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome is a key mediator in mediating inflammatory responses and results in activation of apoptosis signaling pathways. Here we assessed the in vivo and in vitro effects of Qingnao Dripping Pills (QNDP), a traditional Chinese prescription, on inflammatory responses and apoptosis. Our results showed that QNDP could significantly decrease cerebral ischemia injury, improve neurological function and inhibit apoptosis in rats impaired by middle cerebral artery occlusion (MCAO). Further, we found that QNDP inhibited NLRP3 inflammasome expression both in MCAO rats and in SH-SY5Y cells under OGD. Moreover, the levels of inflammatory cytokines including interleukin-1β (IL-1β) and IL-18, which mediated by NLRP3 inflammasome and increased in MCAO rats, could be reduced by QNDP, suggesting that QNDP could protect the neurons against inflammation through a mechanism mediated by NLRP3 inflammasome. Nuclear factor-kappa B (NF-κB) was also involved in the anti-inflammatory effect of QNDP. In conclusion, QNDP had neuroprotective effects against cerebral ischemia via inhibiting NLRP3 inflammasome signaling pathway, and was a potential candidate for the future treatment of ischemic stroke.

Ferroptosis is characterized as a novel form of regulated cell death, which is initiated by the lethal accumulation of lipid peroxidation catalyzed by cellular labile free iron. This iron driven cell death sharply differs from other well characterized forms of regulated cell death at morphological, genetic and biochemical levels. Increasing research has elaborated a high relevance between dysregulated ferroptosis and the pathogenesis of degenerative diseases and organs injury in human patients. Additionally, targeted induction of ferroptosis is considered as a potentially therapeutic design for the clinical intervention of other therapy-resistant cancers. It is well understood that mitochondria, the cellular powerhouse, determine several types of regulated cell death. Recently, compromised mitochondrial morphology and functionalities have been primarily formulated in ferroptosis. Several mitochondria associated proteins and metabolic processes have been elaborated to fine-tune ferroptotic program. Herein, we critically review the recent advances in this booming field, with focus on summarizing the multifaceted mitochondrial regulation of ferroptosis and providing a perspective on the potential biochemical basis. Finally, we are attempting to shed light on an integrative view on the possibility of mitochondria- and ferroptosis-targeting therapeutics as novel treatment designs for the intervention of ferroptosis related diseases.

C17H44Cl4Co4N4O9, triclinic, P1̅ (no. 2), a = 10.918(14) Å, b = 11.899(15) Å, c = 13.327(17) Å, α = 91.286(13)°, β = 91.755(14)°, γ = 111.673(13)°, V = 1607(4) Å3, Z = 2, Rgt(F) = 0.0308, wRref(F2) = 0.1257, T = 293(2) K.

C18H16N6NiO2S2, monoclinic, C2/c (no. 15), a = 14.935(3) Å, b = 8.5054(17) Å, c = 16.268(3) Å, β = 109.45(3)°, V = 1948.5(8) Å3, Z = 4, Rgt(F) = 0.0243, wRref(F2) = 0.0669, T = 293(2) K.

C18H18N2O4, monoclinic, P21/n (no. 14), a = 5.2291(2) Å, b = 10.5932(4) Å, c = 15.3775(6) Å, β = 96.619(2)°, V = 846.13(6) Å3, Z = 4, Rgt(F) = 0.0479, wRref(F2) = 0.1438, T = 293(2) K.

C22H32N2NiO6, monoclinic, C2/c (no. 15), a = 12.7943(7) Å, b = 11.7513(6) Å, c = 16.7322(9) Å, β = 96.337(2)°, V = 2500.3(2) Å3, Z = 4, Rgt(F) = 0.0278, wRref(F2) = 0.0816, T = 293(2) K.