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1.
Ann Surg Oncol ; 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38349564

RESUMO

BACKGROUND: Traditionally, surgical treatment is recommended for right-sided colonic cancer obstruction (RCCO); however, the literature comparing surgical or non-surgical procedures is lacking. METHODS: Patients included in this study were divided into two groups: one group received elective surgery after self-expanding metal stent (SEMS) placement, i.e., the bridge to surgery (BTS) group, and one group received emergency surgery (ES). RESULTS: Thirty-five patients were included in the BTS group and 60 patients underwent ES. The technical and clinical success rates for SEMS placement were 100% and 88.6%, respectively, while the short-term complication rates were 51.4% and 33.3% for the BTS and ES groups, respectively (p = 0.082). Overall, 2.9% and 3.3% of postoperative deaths occurred in the BTS and ES groups (p = 1.000). The 1-year overall survival (OS) rates were 91.4% and 88.3% (p = 0.840), 3-year OS rates were 85.7% and 81.7% (p = 0.860), and 5-year OS rates were 82.9% and 76.7% (p = 0.620) in the BTS and ES groups, respectively. No tumor recurrence was found in the BTS group but seven recurrences were found in the ES group (11.7%) [p = 0.091]. Laparoscopic surgery was chosen by 42.9% of patients in the BTS group and 26.7% of patients in the ES group (p = 0.104); however, the length of hospital stay (p = 0.001) was longer in the BTS group. CONCLUSIONS: In the two groups, no differences were found in terms of postoperative complications and mortality as well as OS. The BTS group preferred to perform laparoscopic surgery and the technical success rate of stenting was high, therefore SEMS for RCCO was considered safe and feasible.

2.
World J Clin Cases ; 12(3): 587-595, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38322461

RESUMO

BACKGROUND: Paramyotonia congenita (PMC) stands as a rare sodium channelopaty of skeletal muscle, initially identified by Eulenburg. The identification of PMC often relies on electromyography (EMG), a diagnostic technique. The child's needle EMG unveiled trains of myotonic discharges with notably giant amplitudes, alongside irregular wave trains of myotonic discharges. This distinctive observation had not surfaced in earlier studies. CASE SUMMARY: We report the case of a 3-year-old female child with PMC, who exhibited laryngeal stridor, muffled speech, myotonia from birth. Cold, exposure to cool water, crying, and physical activity exacerbated the myotonia, which was relieved in warmth, yet never normalized. Percussion myotonia was observable in bilateral biceps. Myotonia symptoms remained unchanged after potassium-rich food consumption like bananas. Hyperkalemic periodic paralysis was excluded. Cranial magnetic resonance imaging yielded normal results. Blood potassium remained within normal range, while creatine kinase showed slight elevation. Exome-wide genetic testing pinpointed a heterozygous mutation on chromosome SCN4A: c.3917G>A (p.G1306E). After a six-month mexiletine regimen, symptoms alleviated. CONCLUSION: In this case revealed the two types of myotonic discharges, and had not been documented in other studies. We underscore two distinctive features: Giant-amplitude potentials and irregular waves.

3.
Eur J Pharmacol ; : 176382, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38311277

RESUMO

Psoriasis is a chronic, recurrent, inflammatory dermatosis accompanied by excessive activation of dendritic cells (DCs), which are primarily responsible for initiating an immune response. The bromodomain and extraterminal domain (BET) family plays a pivotal role in the transcriptional regulation of inflammation and its inhibitors can downregulate DCs maturation and activation. Here we investigated the effect of NHWD-870, a potent BET inhibitor, on inflammation in an imiquimod (IMQ)-induced psoriasis-like mouse model and murine bone marrow-derived dendritic cells (BMDCs) stimulated by lipopolysaccharide (LPS) and IMQ. Application of NHWD-870 significantly ameliorated IMQ-triggered skin inflammation in mice, and markers associated with DC maturation (CD40, CD80 and CD86) were decreased in skin lesions, spleen and lymph nodes. Additionally, NHWD-870 reduced LPS or IMQ induced DCs maturation and activation in vitro, with lower expression of inflammatory cytokines [interleukin (IL)-12, IL-23, tumor necrosis factor-α, IL-6, IL-1ß, chemokine (C-X-C motif) ligand (CXCL)9 and CXCL10]. In addition, we found that interferon regulatory factor 7 (IRF7) significantly increased during DCs maturation, and inhibition of IRF7 could impair BMDCs maturation and activation. What's more, IRF7 was highly expressed in both psoriatic patients and IMQ-induced psoriasis-like mice. Single-cell RNA sequencing of normal and psoriatic skin demonstrated that IRF7 expression was increased in DCs of psoriatic skin. While NHWD-870 could inhibit IRF7 and phosphorylated-IRF7 expression in vivo and in vitro. These results indicate that NHWD-870 suppresses the maturation and activation of DCs by decreasing IRF7 proteins which finally alleviates psoriasis-like skin lesions, and NHWD-870 may be a potent therapeutic drug for psoriasis.

4.
Small ; : e2308525, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38308351

RESUMO

The mortality rate among cancer patients is primarily attributed to tumor metastasis. The evaluation of metastasis potential provides a powerful framework for personalized therapies. However, little work has so far been undertaken to precisely model tumor metastasis in vitro, hindering the development of preventive and therapeutic interventions. In this work, a tumor-metastasis-mimicked Transwell-integrated organoids-on-a-chip platform (TOP) for precisely evaluating tumor metastatic potential is developed. Unlike the conventional Transwell device for detecting cell migration, the engineered device facilitates the assessment of metastasis in patient-derived organoids (PDO). Furthermore, a novel Transwell chamber with a hexagon-shaped structure is developed to mimic the migration of tumor cells into surrounding tissues, allowing for the evaluation of tumor metastasis in a horizontal direction. As a proof-of-concept demonstration, tumor organoids and metastatic clusters are further evaluated at the protein, genetic, and phenotypic levels. In addition, preliminary drug screening is undertaken to highlight the potential for using the device to combat cancers. In summary, the tumor-metastasis-mimicked TOP offers unique capabilities for evaluating the metastasis potential of tumor organoids and contributes to the development of personalized cancer therapies.

5.
Angew Chem Int Ed Engl ; : e202400343, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38323892

RESUMO

Lithium polysulfides (LiPSs) are pivotal intermediates involved in all the cathodic reactions in lithium-sulfur (Li-S) batteries. Elucidating the solvation structure of LiPSs is the first step for rational design of electrolyte and improving Li-S battery performances. Herein, we investigate the solvation structure of LiPSs and find that Li salt anions tend to enter the first solvation sheath of LiPSs and form contact ion pairs in electrolyte. The anion-involved solvation structure of LiPSs significantly influences the intrinsic kinetics of the sulfur redox reactions. In particular, the LiPS solvation structure modified by lithium bis(fluorosulfonyl)imide endows Li-S batteries with reduced polarization and enhanced rate performances under high sulfur areal loading and lean electrolyte volume conditions. This work updates the fundamental understanding of the solvation chemistry of LiPSs and highlights electrolyte engineering for promoting the performances of Li-S batteries.

7.
Adv Sci (Weinh) ; : e2305489, 2024 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-38311578

RESUMO

Keloids are benign fibroproliferative tumors that severely diminish the quality of life due to discomfort, dysfunction, and disfigurement. Recently, ultrasound technology as a noninvasive adjuvant therapy is developed to optimize treatment protocols. However, the biophysical mechanisms have not yet been fully elucidated. Here, it is proposed that piezo-type mechanosensitive ion channel component 1 (Piezo1) plays an important role in low-frequency sonophoresis (LFS) induced mechanical transduction pathways that trigger downstream cellular signaling processes. It is demonstrated that patient-derived primary keloid fibroblasts (PKF), NIH 3T3, and HFF-1 cell migration are inhibited, and PKF apoptosis is significantly increased by LFS stimulation. And the effects of LFS is diminished by the application of GsMTx-4, the selective inhibitor of Piezo1, and the knockdown of Piezo1. More importantly, the effects of LFS can be imitated by Yoda1, an agonist of Piezo1 channels. Establishing a patient-derived xenograft keloid implantation mouse model further verified these results, as LFS significantly decreased the volume and weight of the keloids. Moreover, blocking the Piezo1 channel impaired the effectiveness of LFS treatment. These results suggest that LFS inhibits the malignant characteristics of keloids by activating the Piezo1 channel, thus providing a theoretical basis for improving the clinical treatment of keloids.

8.
Microbes Infect ; : 105307, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38309574

RESUMO

Bacterial DeoR family transcription regulators regulate multiple physiological processes. Little is known about the function of DeoR family regulators in streptococci. Here, we identified a novel DeoR family regulator, GlpR, from Streptococcus suis, a pathogen causing severe diseases in pigs and humans. GlpR was involved in glycerol utilization and exhibited specific signature residues at positions 30-31 (KV) which are crucial for DNA binding. Deletion of glpR (ΔglpR) showed a significant increase in relative growth rate in glycerol medium compared to the wild-type (WT) and complementary strains (CΔglpR). Employing RNA-seq analysis, ß-galactosidase activity analysis, and electrophoretic mobility shift assay, we discovered that GlpR directly represses the expression of glycerol metabolism-related genes pflB2, pflA1, and fsaA, encoding pyruvate formate-lyase and its activating enzyme, and fructose-6-phosphate aldolase, respectively. Compared to WT and CΔglpR, ΔglpR showed a reduced survival rate under oxidative stress and in murine macrophages and attenuated virulence in mice. GlpR probably enhances oxidative stress resistance and virulence in S. suis by functioning as a glycerol metabolic repressor decreasing energy consumption. These findings contribute to a better understanding of S. suis pathogenesis and enrich our knowledge of the biological functions of DeoR family regulators in streptococci.

9.
STAR Protoc ; 5(1): 102874, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310512

RESUMO

Immunophenotyping of out-of-hospital cardiac arrest (OHCA) patients is of increasing interest but has challenges. Here, we describe steps for the design of the clinical cohort, planning patient enrollment and sample collection, and ethical review of the study protocol. We detail procedures for blood sample collection and cryopreservation of peripheral blood mononuclear cells (PBMCs). We detail steps to modulate immune checkpoints in OHCA PBMC ex vivo. This protocol also has relevance for immunophenotyping other types of critical illness. For complete details on the use and execution of this protocol, please refer to Tamura et al. (2023).1.

10.
J Biol Chem ; : 105779, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38395305

RESUMO

The newly discovered zoonotic coronavirus swine acute diarrhea syndrome coronavirus (SADS-CoV) causes acute diarrhea, vomiting, dehydration, and high mortality rates in newborn piglets. Although SADS-CoV uses different strategies to evade the host's innate immune system, the specific mechanism(s) by which it blocks the interferon (IFN) response remains unidentified. In this study, the potential of SADS-CoV nonstructural proteins (nsp) to inhibit the IFN response was detected. The results determined that nsp1 was a potent antagonist of IFN response. SADS-CoV nsp1 efficiently inhibited signal transducer and activator of transcription 1 (STAT1) phosphorylation by inducing Janus kinase 1 (JAK1) degradation. Subsequent research revealed that nsp1 induced JAK1 polyubiquitination through K11 and K48 linkages, leading to JAK1 degradation via the ubiquitin-proteasome pathway. Furthermore, SADS-CoV nsp1 induced CREB-binding protein (CBP) degradation to inhibit IFN-stimulated gene (ISG) production and STAT1 acetylation, thereby inhibiting STAT1 dephosphorylation and blocking STAT1 transport out of the nucleus to receive antiviral signaling. In summary, the results revealed the novel mechanisms by which SADS-CoV nsp1 blocks the JAK-STAT signaling pathway via the ubiquitin-proteasome pathway. This study yielded valuable findings on the specific mechanism of coronavirus nsp1 in inhibiting the JAK-STAT signaling pathway and the strategies of SADS-CoV in evading the host's innate immune system.

11.
Theriogenology ; 218: 254-266, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38367334

RESUMO

Bloom (BLM) helicase plays an important role in DNA replication and the maintenance of genome integrity. BLM protein deficiency, which plays a vital role in the sperm-egg union and germ-cell development during reproduction, can lead to severe DNA damage in goats. However, the effect of BLM protein deficiency on goat litter size has not been reported. Herein, we studied the association between the genetic variation in the BLM gene and the number of kids per litter in Guizhou white goats. We explored differences in the expression of the BLM protein in the follicles of single and multi-kid nanny goats. We also analyzed the effects of dysregulated BLM gene expression on the proliferation and apoptosis of ovarian granulosa cells and the expression of genes related to follicle development in goats. Five single nucleotide polymorphism (SNP) loci, including the non-synonymous mutations g.38179 A > G, g.40626 G > C and g.89621 T > G; the intron synonymous mutation g.56961 G > A and the exon synonymous mutation g.65796 C > T were found in the BLM gene. All SNPs loci were in Hardy-Weinberg equilibrium, and correlation analysis showed that the g.65796 C > T and g.89621 T > G loci polymorphism was strongly associated with litter size in the first three litters (P < 0.05). The diplogenotype Hap 2/2 (AAGGAACCTT) showed no significant difference in litter size between different births, indicating that the diploid genotype is stable in different litter sizes. Bioinformatics analysis showed that three non-synonymous mutation loci (p.T488A, p.A662S, and p.S1373A) could affect BLM protein stability, and mutations in p.T488A and p.S1373A led to changes in amino acid polarity and associated interactions. qPCR results showed that the expression level of the BLM gene in the uterus and ovaries of TT genotype nanny goats was significantly higher than that of GG genotype nanny goats. Indirect immunofluorescence assay (IF) showed that the BLM protein was significantly overexpressed in both the primordial and growing follicles of nanny goats with multiple kids (P < 0.01). Disrupting BLM gene expression in the ovarian granulosa cells down-regulated the expression of the Cyp19A1 gene. It also significantly inhibited the proliferation of follicles and induces early apoptosis of the granulosa cells. These findings confirm that polymorphism in the BLM gene is closely related to the littering traits of Guizhou white goats, and it affects the reproductive performance of nanny goats by regulating the development of the oocytes and granulosa cells. This work provides new evidence on the regulatory effect of the BLM gene on the litter size of nanny goats.

12.
Cell Host Microbe ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38367621

RESUMO

Studies on fecal microbiota transplantation (FMT) have reported inconsistent connections between clinical outcomes and donor strain engraftment. Analyses of subspecies-level crosstalk and its influences on lineage transfer in metagenomic FMT datasets have proved challenging, as single-nucleotide polymorphisms (SNPs) are generally not linked and are often absent. Here, we utilized species genome bin (SGB), which employs co-abundance binning, to investigate subspecies-level microbiome dynamics in patients with autism spectrum disorder (ASD) who had gastrointestinal comorbidities and underwent encapsulated FMT (Chinese Clinical Trial: 2100043906). We found that interactions between donor and recipient microbes, which were overwhelmingly phylogenetically divergent, were important for subspecies transfer and positive clinical outcomes. Additionally, a donor-recipient SGB match was indicative of a high likelihood of strain transfer. Importantly, these ecodynamics were shared across FMT datasets encompassing multiple diseases. Collectively, these findings provide detailed insight into specific microbial interactions and dynamics that determine FMT success.

13.
Zhongguo Zhen Jiu ; 44(2): 144-148, 2024 Feb 12.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-38373758

RESUMO

OBJECTIVES: To observe the clinical efficacy of heat-sensitive moxibustion combined with Xiangwu powder in treating erectile dysfunction with kidney deficiency and blood stasis. METHODS: A total of 80 patients with erectile dysfunction of kidney deficiency and blood stasis were randomly divided into a comprehensive group (40 cases, 1 case dropped out) and a Chinese herb group (40 cases, 2 cases dropped out). In the Chinese herb group, Xiangwu powder was applied orally, one dose per day. On the basis of the Chinese herb group, heat-sensitive moxibustion was applied after detecting the heat-sensitive points in the areas of Guanyuan (CV 4), Zhongji (CV 3), Qihai (CV 6) and bilateral Xuehai (SP 10), Sanyinjiao (SP 6) in the comprehensive group, once a day, 5 times a week. Both groups were treated for 4 weeks. The international index of erectile function-5 (IIEF-5) score, erectile hardness score (EHS), nocturnal penile tumescence and rigidity (NPTR) indexes (nocturnal penile erection frequency, total duration of penile erection, duration of penile head hardness ≥60%, duration of penile root hardness ≥60%, percentage change in penile head circumference, percentage change in penile root circumference), TCM syndrome score, and penile vascular function indexes (peak systolic velocity [PSV], end diastolic velocity [EDV], and resistance index [RI] of penile cavernosal artery) were compared in the patients of the two groups before and after treatment, and the clinical efficacy was evaluated. RESULTS: After treatment, the IIEF-5 scores, EHS, PSV, RI, and NPTR indexes were increased compared with those before treatment (P<0.01), while the TCM syndrome scores and EDV were decreased compared with those before treatment (P<0.01) in the two groups.The IIEF-5 score, EHS, PSV, RI, and NPTR indexes in the comprehensive group were ascended compared with those in the Chinese herb group (P<0.01), while the TCM syndrome score and EDV in the comprehensive group were lower than those in the traditional Chinese herb group (P<0.01). The total effective rate of the comprehensive group was 94.9% (37/39), which was higher than 78.9% (30/38, P<0.05) of the Chinese herb group. CONCLUSIONS: The combination of heat-sensitive moxibustion and Xiangwu powder can effectively treat erectile dysfunction of kidney deficiency and blood stasis, improve patients' erectile function, enhance their erection hardness, and improve their penile vascular function and clinical symptoms.


Assuntos
Disfunção Erétil , Moxibustão , Masculino , Humanos , Disfunção Erétil/tratamento farmacológico , Pós/uso terapêutico , Temperatura Alta , Rim
14.
EMBO J ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360993

RESUMO

Most cellular ubiquitin signaling is initiated by UBA1, which activates and transfers ubiquitin to tens of E2 enzymes. Clonally acquired UBA1 missense mutations cause an inflammatory-hematologic overlap disease called VEXAS (vacuoles, E1, X-linked, autoinflammatory, somatic) syndrome. Despite extensive clinical investigation into this lethal disease, little is known about the underlying molecular mechanisms. Here, by dissecting VEXAS-causing UBA1 mutations, we discovered that p.Met41 mutations alter cytoplasmic isoform expression, whereas other mutations reduce catalytic activity of nuclear and cytoplasmic isoforms by diverse mechanisms, including aberrant oxyester formation. Strikingly, non-p.Met41 mutations most prominently affect transthioesterification, revealing ubiquitin transfer to cytoplasmic E2 enzymes as a shared property of pathogenesis amongst different VEXAS syndrome genotypes. A similar E2 charging bottleneck exists in some lung cancer-associated UBA1 mutations, but not in spinal muscular atrophy-causing UBA1 mutations, which instead, render UBA1 thermolabile. Collectively, our results highlight the precision of conformational changes required for faithful ubiquitin transfer, define distinct and shared mechanisms of UBA1 inactivation in diverse diseases, and suggest that specific E1-E2 modules control different aspects of tissue differentiation and maintenance.

15.
Diagn Interv Imaging ; 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38378382

RESUMO

PURPOSE: The purpose of this study was to evaluate the incremental diagnostic value of virtual non-contrast (VNC) images derived from unenhanced dual-energy computed tomography (CT) for the diagnosis of choledocholithiasis by comparison with conventional unenhanced CT. MATERIALS AND METHODS: Eighty-nine patients with gallbladder stones who had undergone both abdominal unenhanced dual-energy CT and magnetic resonance cholangiopancreatography (MRCP) were retrospectively included. There were 53 men and 36 women, with a mean age of 54 ± 13 (standard deviation) years (age range: 41-67 years). VNC and conventional CT images were generated. Two independent radiologists evaluated the presence of choledocholithiasis in three reading sessions (session 1, conventional unenhanced CT images; session 2, VNC images; session 3, conventional unenhanced CT plus VNC images). The reading time to identify choledocholithiasis was recorded. Inter-reader agreement was measured by using the Cohen kappa (κ) test. Incremental diagnostic value of VNC imaging when combined with conventional unenhanced CT was assessed based on discrimination (area under the curve [AUC]) and clinical utility (decision curve analysis). The diagnostic performance of dual-energy CT and that of MRCP were compared using DeLong test. RESULTS: Using the standard of reference, 39 patients (39/89; 44%) had choledocholithiasis. The diagnosis of choledocholithiasis was improved using VNC images in combination with conventional unenhanced CT (AUC, 0.877; 95% confidence interval [CI]: 0.808, 0.947) by comparison with conventional unenhanced CT alone (AUC, 0.789; 95% CI: 0.718, 0.877) (P = 0.033) and achieved almost perfect inter-reader agreement (κ = 0.88; 95% CI: 0.72, 1.00) for the diagnosis of choledocholithiasis, without lengthening the median reading time (16.2 s for the combination of conventional CT and VNC images vs. 14.7 s for conventional CT alone; P= 0.325). Based on decision curve analysis, adding VNC imaging to conventional unenhanced CT resulted in a higher net benefit among most of decision thresholds. No differences in diagnostic performance were found between the combination of conventional unenhanced CT and VNC imaging (AUC, 0.877; 95% CI: 0.808, 0.947) and MRCP (AUC, 0.913; 95% CI: 0.852, 0.974) (P= 0.458). CONCLUSIONS: VNC images derived from dual-energy unenhanced CT have incremental diagnostic value for the diagnosis of choledocholithiasis. Unenhanced CT in a dual-energy mode may be a useful tool for the diagnosis of choledocholithiasis.

16.
J Trop Pediatr ; 70(2)2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38366669

RESUMO

OBJECTIVE: This study aims to investigate determinants impacting the surgical management of splenic trauma in paediatric patients by scrutinizing age distribution, etiological factors and concomitant injuries. The analysis seeks to establish a foundation for delineating optimal operative timing. METHODS: A cohort of 262 paediatric cases presenting with splenic trauma at our institution from January 2011 to December 2021 underwent categorization into either the conservative or operative group. RESULTS: Significantly disparate attributes between the two groups included age, time of presentation, blood pressure, haemoglobin levels, blood transfusion requirements, thermal absorption, American Association for the Surgery of Trauma (AAST) classification and associated injuries. Logistic regression analysis revealed age, haemoglobin levels, AAST classification and blood transfusion as autonomous influencers of surgical intervention (OR = 1.024, 95% CI: 1.011-1.037; OR = 1.067, 95% CI: 1.01-1.127; OR = 0.2760, 95% CI: 0.087-0.875; OR = 7.873, 95% CI: 2.442-25.382; OR = 0.016, 95% CI: 0.002-0.153). The AAST type and age demonstrated areas under the receiver operating characteristic (ROC) curve of 0.782 and 0.618, respectively. CONCLUSION: Age, haemoglobin levels, AAST classification and blood transfusion independently influence the decision for surgical intervention in paediatric patients with splenic trauma. Age and AAST classification emerge as viable parameters for assessing and prognosticating the likelihood of surgical intervention in this patient cohort.


Assuntos
Traumatismos Abdominais , Ferimentos não Penetrantes , Humanos , Criança , Baço/cirurgia , Estudos Retrospectivos , Ferimentos não Penetrantes/cirurgia , Traumatismos Abdominais/cirurgia , Hemoglobinas , Escala de Gravidade do Ferimento
18.
J Biol Chem ; : 105772, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38382674

RESUMO

Pre-mRNA splicing is a precise regulated process, and is crucial for system development and homeostasis maintenance. Mutations in spliceosomal components have been found in various hematopoietic malignancies (HMs), and have been considered as oncogenic derivers of HMs. However, the role of spliceosomal components in normal and malignant hematopoiesis remain largely unknown. Pre-mRNA processing factor 31 (PRPF31) is a constitutive spliceosomal component, which mutations are associated with autosomal dominant retinitis pigmentosa. PRPF31 was found to be mutated in several HMs, but the function of PRPF31 in normal hematopoiesis has not been explored. In our previous study, we generated a prpf31 knockout zebrafish line, and reported that Prpf31 regulates the survival and differentiation of retinal progenitor cells (RPCs) by modulating the alternative splicing of genes involved in mitosis and DNA repair. In this study, by using the prpf31 knockout zebrafish line, we discovered that prpf31 knockout zebrafish exhibited severe defects in hematopoietic stem and progenitor cell (HSPC) expansion and its sequentially differentiated lineages. Immunofluorescence results showed that Prpf31 deficient HSPCs underwent malformed mitosis and M phase arrest during HSPC expansion. Transcriptome analysis and experimental validations revealed that Prpf31 deficiency extensively perturbed the alternative splicing of mitosis-related genes. Collectively, our findings elucidate a previously undescribed role for Prpf31 in HSPC expansion, through regulating the alternative splicing of mitosis-related genes.

19.
Sci Total Environ ; 917: 170502, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38301791

RESUMO

The use of lanthanum-modified bentonite (LMB) combined with Vallisneria spiralis (V∙s) (LMB + V∙s) is a common method for controlling internal phosphorus (P) release from sediments. However, the behaviors of iron (Fe) and manganese (Mn) under LMB + V∙s treatments, as well as the associated coupling effect on P, dissolved organic matter (DOM), and heavy metal(loid)s (HMs), require further investigations. Therefore, we used in this study a microelectrode system and high-resolution dialysis technology (HR-Peeper) to study the combined effects of LMB and V∙s on P, DOM, and HMs through a 66-day incubation experiment. The LMB + V∙s treatment increased the sediment DO concentration, promoting in-situ formations of Fe (III)/Mn (IV) oxyhydroxides, which, in turn, adsorbed P, soluble tungsten (W), DOM, and HMs. The increase in the concentrations of HCl-P, amorphous and poorly crystalline (oxyhydr) oxides-bound W, and oxidizable HMs forms demonstrated the capacity of the LMB + V∙s treatment to transform mobile P, W, and other HMs forms into more stable forms. The significant positive correlations between SRP, soluble W, UV254, and soluble Fe (II)/Mn, and the increased concentrations of the oxidizable HMs forms suggested the crucial role of the Fe/Mn redox in controlling the release of SRP, DOM, and HMs from sediments. The LMB + V∙s treatment resulted in SRP, W, and DOM removal rates of 74.49, 78.58, and 54.78 %, which were higher than those observed in the control group (without LMB and V∙s applications). On the other hand, the single and combined uses of LMB and V·s influenced the relative abundances of the sediment microbial communities without exhibiting effects on microbial diversity. This study demonstrated the key role of combined LMB and V∙s applications in controlling the release of P, W, DOM, and HMs in eutrophic lakes.


Assuntos
Hydrocharitaceae , Metais Pesados , Fósforo/química , Matéria Orgânica Dissolvida , Bentonita/química , Lantânio/química , Diálise Renal , Manganês/análise , Lagos/química , Sedimentos Geológicos/química
20.
Front Microbiol ; 15: 1301258, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38348184

RESUMO

Livestock on the Qinghai-Tibetan Plateau is of great importance for the livelihood of the local inhabitants and the ecosystem of the plateau. The natural, harsh environment has shaped the adaptations of local livestock while providing them with requisite eco-services. Over time, unique genes and metabolic mechanisms (nitrogen and energy) have evolved which enabled the yaks to adapt morphologically and physiologically to the Qinghai-Tibetan Plateau. The rumen microbiota has also co-evolved with the host and contributed to the host's adaptation to the environment. Understanding the complex linkages between the rumen microbiota, the host, and the environment is essential to optimizing the rumen function to meet the growing demands for animal products while minimizing the environmental impact of ruminant production. However, little is known about the mechanisms of host-rumen microbiome-environment linkages and how they ultimately benefit the animal in adapting to the environment. In this review, we pieced together the yak's adaptation to the Qinghai-Tibetan Plateau ecosystem by summarizing the natural selection and nutritional features of yaks and integrating the key aspects of its rumen microbiome with the host metabolic efficiency and homeostasis. We found that this homeostasis results in higher feed digestibility, higher rumen microbial protein production, higher short-chain fatty acid (SCFA) concentrations, and lower methane emissions in yaks when compared with other low-altitude ruminants. The rumen microbiome forms a multi-synergistic relationship among the rumen microbiota services, their communities, genes, and enzymes. The rumen microbial proteins and SCFAs act as precursors that directly impact the milk composition or adipose accumulation, improving the milk or meat quality, resulting in a higher protein and fat content in yak milk and a higher percentage of protein and abundant fatty acids in yak meat when compared to dairy cow or cattle. The hierarchical interactions between the climate, forage, rumen microorganisms, and host genes have reshaped the animal's survival and performance. In this review, an integrating and interactive understanding of the host-rumen microbiome environment was established. The understanding of these concepts is valuable for agriculture and our environment. It also contributes to a better understanding of microbial ecology and evolution in anaerobic ecosystems and the host-environment linkages to improve animal production.

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