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1.
Gynecol Endocrinol ; 40(1): 2351525, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38726683

RESUMO

OBJECTIVE: Stable luteal cell function is an important prerequisite for reproductive ability and embryonic development. However, luteal insufficiency seriously harms couples who have the desire to have a pregnancy, and the most important thing is that there is no complete solution. In addition, Vaspin has been shown to have regulatory effects on luteal cells, but the complex mechanisms involved have not been fully elucidated. Therefore, this study aimed to explore the effect of Vaspin on rat luteal cells and its mechanism. METHODS: Granulosa lutein cells separated from the ovary of female rats were incubated for 24h with gradient concentrations of Vaspin, and granulosa lutein cells incubated with 0.5% bovine serum albumin were used as controls. The proliferation, apoptosis, angiogenesis, progesterone (P4) and estradiol (E2) were detected by CCK-8, Anneixn-FITC/PI staining, angiogenesis experiment and ELISA. Western blot was applied to observe the expression levels of proteins related to cell proliferation, apoptosis, angiogenesis and MEK/MAPK signaling pathway. RESULTS: Compared with the Control group, Vaspin could significantly up-regulate the proliferation of granulosa lutein cells and reduce the apoptosis. Moreover, Vaspin promoted the angiogenesis of granulosa lutein cells and the production of P4 and E2 in a concentration-dependent manner. Furthermore, Vaspin up-regulated the CyclinD1, CyclinB1, Bcl2, VEGFA and FGF-2 expression in granulosa lutein cells, and down-regulated the level of Bax. Also, Vaspin increased the p-MEK1 and p-p38 levels. CONCLUSION: Vaspin can up-regulate the proliferation and steroidogenesis of rat luteal cells and reduce apoptosis, which may be related to the influence of MEK/MAPK activity.


Assuntos
Apoptose , Proliferação de Células , Células Lúteas , Progesterona , Serpinas , Animais , Feminino , Proliferação de Células/efeitos dos fármacos , Serpinas/metabolismo , Serpinas/farmacologia , Ratos , Células Lúteas/efeitos dos fármacos , Células Lúteas/metabolismo , Apoptose/efeitos dos fármacos , Progesterona/farmacologia , Estradiol/farmacologia , Células Cultivadas , Ratos Sprague-Dawley , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos
2.
Sci Rep ; 14(1): 9149, 2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38644401

RESUMO

Taking thin gauge strip as an example, the deformation process of metal strip in bending roll straightening was studied. Based on the theory of discrete, curvature integral and elastic-plastic mechanics, the strip travel trajectory of the bending roll straightening process is analyzed, and the numerical analytical calculation method of the continuous straightening process of the strip bending roll is established. The results are verified by establishing MARC finite element simulation and designing straightening experiment. The effects of yield strength, plastic rate and bending amount on residual stress after straightening were studied. In the straightening process, with the increase of the amount of bending roll, the residual strain converges to the region Γ, and with the increase of the yield strength, the region Γ decreases. With the increase of the yield strength, the amount of bending roll and the plastic rate, the wave height increases. The results of the calculation of residual stress, finite element simulation and experiment are close and the trend is consistent. The results show that the logic of the calculation method is reasonable, and the prediction error is within the scope of engineering application, which is helpful to the realization of process intelligence in the process of bending roller straightening.

3.
Sci Bull (Beijing) ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38670850

RESUMO

The merging of transition metal catalysis with electrochemistry has become a powerful tool for organic synthesis because catalysts can govern the reactivity and selectivity. However, coupling catalysts with alkyl radical species generated by anodic oxidation remains challenging because of electrode passivation, dimerization, and overoxidation. In this study, we developed convergent paired electrolysis for the coupling of nickel catalysts with alkyl radicals derived from photoinduced ligand-to-metal charge-transfer of cyclic alcohols and iron catalysts, providing a practical method for site-specific and remote arylation of ketones. The synergistic use of photocatalysis with convergent paired electrolysis can provide alternative avenues for metal-catalyzed radical coupling reactions.

4.
Plant Cell ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652680

RESUMO

Flowering is a key developmental transition in the plant life cycle. In temperate climates, flowering often occurs in response to the perception of seasonal cues such as changes in day-length and temperature. However, the mechanisms that have evolved to control the timing of flowering in temperate grasses are not fully understood. We identified a Brachypodium distachyon mutant whose flowering is delayed under inductive long-day conditions due to a mutation in the JMJ1 gene, which encodes a Jumonji domain-containing protein. JMJ1 is a histone demethylase that mainly demethylates H3K4me2 and H3K4me3 in vitro and in vivo. Analysis of the genome-wide distribution of H3K4me1, H3K4me2, and H3K4me3 in wild-type plants by chromatin immunoprecipitation and sequencing (ChIP-seq) combined with RNA sequencing (RNA-seq) revealed that H3K4m1 and H3K4me3 are positively associated with gene transcript levels, whereas H3K4me2 is negatively correlated with transcript levels. Furthermore, JMJ1 directly binds to the chromatin of the flowering regulator genes VRN1 and ID1 and affects their transcription by modifying their H3K4me2 and H3K4me3 levels. Genetic analyses indicated that JMJ1 promotes flowering by activating VRN1 expression. Our study reveals a role for JMJ1-mediated chromatin modification in the proper timing of flowering in B. distachyon.

5.
Food Chem X ; 22: 101312, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38559444

RESUMO

Protein glutaminase (PG), originating from Chryseobacterium proteolyticum, can catalyze the deamidation of glutamine residues in plant proteins into glutamic acid, thus enhancing its functional properties. However, the low yield of PG limits its industrial production. In this study, the yield of PG in C. proteolyticum TM1040 increased by 121 %, up to 7.30 U/mL in a 15 L fermenter after medium optimization. Subsequently, purified PG was obtained by cation exchange chromatography (CEX) coupled with hydrophobic interaction chromatography (HIC). The degree of deamidation (DD) of wheat gluten after purified PG deamidation was 87.11 %, which is superior to chemical deamidation in safety and DD. The emulsifying and foaming properties of deamidated wheat gluten were 2.67 and 18.86 times higher, and the water- and oil-holding properties were 4.23 and 18.77 times higher, respectively. The deamidated wheat gluten with enhanced functional properties was used to improve the flavor and texture in baking cakes.

6.
Br J Haematol ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581290

RESUMO

To explore the impact of letermovir (LET) prophylaxis on cytomegalovirus (CMV) reactivation and resistance in both adult and paediatric umbilical cord blood transplantation (UCBT) patients, we retrospectively compared 43 UCBT patients who received LET as CMV prophylaxis with a historical cohort of 207 UCBT patients without LET usage. LET was administered from Day +1 to Day +100. The 180-day cumulative incidence of CMV reactivation (47.3% vs. 74.4%, p < 0.001) and the proportion of refractory CMV reactivation (15.0% vs. 42.9%, p = 0.016) were significantly lower than those in the control group. However, more frequent late CMV infection (31.0% vs. 4.3%, p = 0.002) and the 180-day cumulative incidence of Epstein-Barr virus (EBV) reactivation (9.3% vs. 3.4%, p = 0.087) were observed in UCBT patients with LET prophylaxis. Meanwhile, older age (>15 years old) and the occurrence of pre-engraftment syndrome were identified as the significant risk factors for CMV reactivation, and in patients at high risk, the incidence of CMV reactivation in the LET group was lower than that in the control group (46.7% vs. 86.5%, p < 0.001), while this decline was less pronounced among patients at low risk (47.8% vs. 62.1%, p = 0.120).

7.
Bioorg Med Chem Lett ; 107: 129769, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38670537

RESUMO

Among small-molecule CDK4/6 inhibitors (palbociclib, ribociclib, and abemaciclib) approved for metastatic breast cancers, abemaciclib has a more tolerable adverse effects in clinic. This is attributable to preferential inhibition of CDK4 over CDK6. In our search for a biased CDK4 inhibitor, we discovered a series of pyrimidine-indazole inhibitors. SAR studies led us to TQB3616 as a preferential CDK4 inhibitor. TQB3616 exhibited improvements in both enzymatic and cellular proliferation inhibitory potency when tested side-by-side with the FDA approved palbociclib and abemaciclib. TQB3616 also possessed favorable PK profile in multiple species. These differentiated properties, together with excellent GLP safety profile warranted TQB3616 moving to clinic. TQB3616 entered into clinical development in 2019 and currently in phase III clinical trials (NCT05375461, NCT05365178).

8.
Br J Haematol ; 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38664918

RESUMO

In this multicentre, real-world study, we aimed to identify the clinical outcomes and safety of allogeneic haematopoietic stem cell transplantation (allo-HSCT) in T-lymphoblastic lymphoma (T-LBL). A total of 130 Ann Arbor stage III or IV T-LBL patients (>16 years) treated with allo-HSCT across five transplant centres were enrolled. The 2-year cumulative incidence of disease progression, the probabilities of progression-free survival (PFS), overall survival (OS) and non-relapse mortality (NRM) after allo-HSCT were 21.0%, 69.8%, 79.5% and 9.2% respectively. Patients with central nervous system (CNS) involvement had a higher cumulative incidence of disease progression compared with those without CNS involvement (57.1% vs. 18.9%, HR 3.78, p = 0.014). Patients receiving allo-HSCT in non-remission (NR) had a poorer PFS compared with those receiving allo-HSCT in complete remission (CR) or partial remission (49.2% vs. 72.7%, HR 2.21, p = 0.041). Particularly for patients with bone marrow involvement and achieving CR before allo-HSCT, measurable residual disease (MRD) positivity before allo-HSCT was associated with a poorer PFS compared with MRD negativity (62.7% vs. 86.8%, HR 1.94, p = 0.036). On multivariate analysis, CNS involvement at diagnosis and receiving allo-HSCT in NR were associated with disease progression. Thus, our real-world data suggested that allo-HSCT appeared to be an effective therapy for adult T-LBL patients with Ann Arbor stage III or IV disease.

9.
Exp Biol Med (Maywood) ; 249: 10137, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655370

RESUMO

Azoospermia is a serious leading male-factor cause of infertility in couples of childbearing age. The two main azoospermia types, obstructive (OA) and non-obstructive (NOA) azoospermia, differ in their treatment approaches. Therefore, their clinical diagnosis is extremely important, requiring an accurate, efficient, and easy-to-use diagnostic model. This retrospective observational study included 707 patients with azoospermia treated between 2017 and 2021, 498 with OA, and 209 with NOA. Hematological and seminal plasma parameters, hormone levels, and testicular volume were used in logistic regression analysis to evaluate and compare their diagnostic performance, results showed that the optimal diagnostic model is constructed by five variables including semen volume, semen pH, seminal plasma neutral α-glucosidase activity, follicle-stimulating hormone in the serum, and testicular volume, compared with follicle-stimulating hormone-based and testicular volume-based models. The 5-factor diagnostic model had an accuracy of 90.4%, sensitivity of 96.4%, positive predictive value of 90.6%, negative predictive value of 89.8%, and area under the curve of 0.931, all higher than in the other two models. However, its specificity (76.1%) was slightly lower than in the other models. Meantime, the internal 5-fold cross-validation results indicated that the 5-factor diagnostic model had a good clinical application value. This study established an accurate, efficient, and relatively accessible 5-factor diagnostic model for OA and NOA, providing a reference for clinical decision-making when selecting an appropriate treatment.


Assuntos
Azoospermia , Hormônio Foliculoestimulante , Testículo , Adulto , Humanos , Masculino , Azoospermia/diagnóstico , Azoospermia/sangue , Hormônio Foliculoestimulante/sangue , Estudos Retrospectivos , Sêmen/metabolismo , Análise do Sêmen/métodos , Testículo/patologia
10.
Polymers (Basel) ; 16(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38675095

RESUMO

The biaxially-oriented PA56/512 has excellent mechanical strength, extensibility and water-oxygen barrier properties and has broad application prospects in green packaging, lithium battery diaphragm and medical equipment materials. The correlation between the aggregation structure evolution and macroscopic comprehensive properties of copolymer PA56/512 under biaxial stretching has been demonstrated in this work. The structure of the random copolymerization sequence was characterized by 13C Nuclear magnetic resonance (NMR). The typical isodimorphism behavior of the co-crystallization system of PA56/512 and its BOPA-56/512 films was revealed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) tests. And the aggregation structure, including the hydrogen bond arrangement, crystal structure and crystal morphology of PA56/512 before and after biaxial stretching, was investigated by XRD, Fourier-transform infrared spectroscopy (FTIR) and polarized optical microscopy (POM) tests. Furthermore, the effect of the biaxially-oriented stretching process on the mechanical properties of PA56/512 has been demonstrated. In addition, a deep insight into the influence of the structure on the crystallization process and physical-mechanical performance has been presented. The lowest melting point at a 512 content of 60 mol% is regarded as a "eutectic" point of the isodimorphism system. Due to the high disorder of the structural units in the polymer chain, the transition degree of the folded chain (gauche conformation) is relatively lowest when it is straightened to form an extended chain (trans conformation) during biaxially-oriented stretching, and part of the folded chain can be retained. This explains why biaxially stretched PA56/512 has high strength, outstanding toughness and excellent barrier properties at the pseudo-eutectic point. In this study, using the unique multi-scale aggregation structure characteristics of a heterohomodymite polyamide at the pseudo-eutectic point, combined with the new material design scheme and the idea of biaxial-stretching processing, a new idea for customized design of high-performance multifunctional polyamide synthetic materials is provided.

11.
MMWR Morb Mortal Wkly Rep ; 73(12): 255-259, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38547027

RESUMO

Gonorrhea is a widespread sexually transmitted infection; in 2022, China reported 96,313 cases of gonorrhea, making it the fourth most common notifiable infectious disease in the country after viral hepatitis, pulmonary tuberculosis, and syphilis. The rise in prevalence in antimicrobial-resistant strains, particularly the international spread of ceftriaxone-resistant clones, poses a formidable challenge to gonorrhea control. The China Gonococcal Resistance Surveillance Program (China-GRSP), established in 1987 and covering 19 of 34 provincial-level administrative units, continuously monitors gonococcal antimicrobial resistance. In 2022, 13 China-GRSP sentinel sites collected 2,804 gonococcal isolates, representing 2.9% of all cases reported in China, and 4.1% of cases reported in the 13 participating provinces. The prevalence of Neisseria gonorrhoeae resistance to ceftriaxone was 8.1%, approximately three times the 2017 rate of 2.9%; five provinces reported >10% ceftriaxone resistance. Resistance prevalences to cefixime, azithromycin, tetracycline, penicillin, and ciprofloxacin were 16.0%, 16.9%, 77.1%, 77.8%, and 97.6%, respectively. Only one case of spectinomycin resistance was reported. These data highlight a substantial increase in ceftriaxone resistance from 2017 to 2022. Effective diagnosis and treatment and appropriate management of sex partners are essential to protect the health of infected persons and prevent ongoing transmission of gonorrhea, including transmission of resistant strains. Identifying reasons for the spread of ceftriaxone-resistant N. gonorrhoeae in China could guide strategies, such as antibiotic stewardship, to mitigate the rising resistance rate and curb the spread of resistant strains.


Assuntos
Anti-Infecciosos , Gonorreia , Humanos , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ciprofloxacina , Neisseria gonorrhoeae , Azitromicina , Anti-Infecciosos/farmacologia , China/epidemiologia , Farmacorresistência Bacteriana
12.
Front Endocrinol (Lausanne) ; 15: 1328579, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38524629

RESUMO

Background: Owing to individual heterogeneity, patients with idiopathic membranous nephropathy (IMN) exhibit varying sensitivities to immunotherapy. This study aimed to establish and validate a model incorporating pathological and clinical features using deep learning training to evaluate the response of patients with IMN to immunosuppressive therapy. Methods: The 291 patients were randomly categorized into training (n = 219) and validation (n = 72) cohorts. Patch-level convolutional neural network training in a weakly supervised manner was utilized to analyze whole-slide histopathological features. We developed a machine-learning model to assess the predictive value of pathological signatures compared to clinical factors. The performance levels of the models were evaluated using the area under the receiver operating characteristic curve (AUC) on the training and validation tests, and the prediction accuracies of the models for immunotherapy response were compared. Results: Multivariate analysis indicated that diabetes and smoking were independent risk factors affecting the response to immunotherapy in IMN patients. The model integrating pathologic features had a favorable predictive value for determining the response to immunotherapy in IMN patients, with AUCs of 0.85 and 0.77 when employed in the training and test cohorts, respectively. However, when incorporating clinical features into the model, the predictive efficacy diminishes, as evidenced by lower AUC values of 0.75 and 0.62 on the training and testing cohorts, respectively. Conclusions: The model incorporating pathological signatures demonstrated a superior predictive ability for determining the response to immunosuppressive therapy in IMN patients compared to the integration of clinical factors.


Assuntos
Aprendizado Profundo , Glomerulonefrite Membranosa , Humanos , Glomerulonefrite Membranosa/tratamento farmacológico , Rim/patologia , Análise Multivariada , Imunoterapia
13.
Sci Rep ; 14(1): 5545, 2024 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448553

RESUMO

Quantitative analysis of the biologically-active metabolites of vitamin D (VitD), which are crucial in regulating various physiological and pathological processes, is important for clinical investigations. Liquid chromatography-tandem mass spectrometry (LC-MS) has been widely used for this purpose but existing LC-MS methods face challenges in achieving highly sensitive and accurate quantification of low-abundance VitD metabolites while maintaining high throughput and robustness. Here we developed a novel pipeline that combines a trapping-micro-LC-(T-µLC) with narrow-window-isolation selected-reaction monitoring MS(NWI-SRM) for ultra-sensitive, robust and high-throughput quantification of VitD metabolites in serum samples after derivatization. The selective-trapping and delivery approach efficiently removes matrix components, enabling high-capacity sample loading and enhancing sensitivity, throughput, and robustness. The NWI-SRM further improves the sensitivity by providing high selectivity. The lower limits of quantification (LOQs) achieved were markedly lower than any existing LC-MS methods: 1.0 pg/mL for 1,25(OH)2D3, 5.0 pg/mL for 24,25(OH)2D3, 30 pg/mL for both 25(OH)D2 and 25(OH)D3, all within a 9-min cycle. The method is applied to quantify VitD metabolites from 218 patients with multiple sclerosis. This study revealed negative correlations(r=- 0.44 to - 0.51) between the levels of 25(OH)D2 and all the three D3 metabolites in multiple sclerosis patients.


Assuntos
Espectrometria de Massa com Cromatografia Líquida , Esclerose Múltipla , Humanos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Vitamina D
14.
Small ; : e2308861, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38372029

RESUMO

The anabolism of tumor cells can not only support their proliferation, but also endow them with a steady influx of exogenous nutrients. Therefore, consuming metabolic substrates or limiting access to energy supply can be an effective strategy to impede tumor growth. Herein, a novel treatment paradigm of starving-like therapy-triple energy-depleting therapy-is illustrated by glucose oxidase (GOx)/dc-IR825/sorafenib liposomes (termed GISLs), and such a triple energy-depleting therapy exhibits a more effective tumor-killing effect than conventional starvation therapy that only cuts off one of the energy supplies. Specifically, GOx can continuously consume glucose and generate toxic H2 O2 in the tumor microenvironment (including tumor cells). After endocytosis, dc-IR825 (a near-infrared cyanine dye) can precisely target mitochondria and exert photodynamic and photothermal activities upon laser irradiation to destroy mitochondria. The anti-angiogenesis effect of sorafenib can further block energy and nutrition supply from blood. This work exemplifies a facile and safe method to exhaust the energy in a tumor from three aspects and starve the tumor to death and also highlights the importance of energy depletion in tumor treatment. It is hoped that this work will inspire the development of more advanced platforms that can combine multiple energy depletion therapies to realize more effective tumor treatment.

15.
Plant J ; 2024 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-38402593

RESUMO

Plant cell walls are essential for defining plant growth and development, providing structural support to the main body and responding to abiotic and biotic cues. Cellulose, the main structural polymer of plant cell walls, is synthesized at the plasma membrane by cellulose synthase complexes (CSCs). The construction and transport of CSCs to and from the plasma membrane is poorly understood but is known to rely on the coordinated activity of cellulose synthase-interactive protein 1 (CSI1), a key regulator of CSC trafficking. In this study, we found that Trs85, a TRAPPIII complex subunit, interacted with CSI1 in vitro. Using functional genetics and live-cell imaging, we have shown that trs85-1 mutants have reduced cellulose content, stimulated CSC delivery, an increased population of static CSCs and deficient clathrin-mediated endocytosis in the primary cell wall. Overall, our findings suggest that Trs85 has a dual role in the trafficking of CSCs, by negatively regulating the exocytosis and clathrin-mediated endocytosis of CSCs.

16.
Sci Total Environ ; 920: 171014, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38369163

RESUMO

With the rapid development of the economy, household activities have emerged as an important source of greenhouse gas (GHG) emissions, making them a crucial focal point for research in the pursuit of sustainable development and carbon emission reduction. Hulunber, as a typical steppe region in eastern Eurasia, is representative of studying the GHG emissions from household ranches, which are the basic production units in this region. In this paper, based on survey data of 2018 and 2019, we quantified and assessed GHG emissions from household ranches by combining life cycle assessment (LCA) and structural equation modeling (SEM) approaches, with LCA to define household ranches system boundary and SEM to determine the key driving factors of emissions. The results showed that GHG emissions of meat sheep live weight was 23.54 kg CO2-eq/kg. The major contributor to household GHG emissions was enteric methane (55.23 %), followed by coal use (20.80 %) and manure management systems (9.16 %), and other contributing factors (14.81 %). The SEM results indicated that the GHG emissions from household ranches were derived primarily by economic level, while the economic level was significantly affected by income. This study also found a significant positive and linear correlation between household GHG emissions and the number of meat sheep (R2 = 0.89, P < 0.001). The GHG emissions from meat sheep production (67.52 %) were double times greater than household livelihood consumption (32.48 %). These findings emphasized the importance of reducing emissions from meat sheep production and adjusting the energy mix of household livelihood, contributing to the establishment of a low-carbon household livelihood operation.


Assuntos
Gases de Efeito Estufa , Animais , Ovinos , Gases de Efeito Estufa/análise , Efeito Estufa , Pradaria , Carbono , Carne
17.
J Med Genet ; 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341271

RESUMO

BACKGROUND: The association between the TDRD6 variants and human infertility remains unclear, as only one homozygous missense variant of TDRD6 was found to be associated with oligoasthenoteratozoospermia (OAT). METHODS: Whole-exome sequencing and Sanger sequencing were employed to identify potential pathogenic variants of TDRD6 in infertile men. Histology, immunofluorescence, immunoblotting and ultrastructural analyses were conducted to clarify the structural and functional abnormalities of sperm in mutated patients. Tdrd6-knockout mice were generated using the CRISPR-Cas9 system. Total RNA-seq and single-cell RNA-seq (scRNA-seq) analyses were used to elucidate the underlying molecular mechanisms, followed by validation through quantitative RT-PCR and immunostaining. Intracytoplasmic sperm injection (ICSI) was also used to assess the efficacy of clinical treatment. RESULTS: Bi-allelic TDRD6 variants were identified in five unrelated Chinese individuals with OAT, including homozygous loss-of-function variants in two consanguineous families. Notably, besides reduced concentrations and impaired motility, a significant occurrence of acrosomal hypoplasia was detected in multiple spermatozoa among five patients. Using the Tdrd6-deficient mice, we further elucidate the pivotal role of TDRD6 in spermiogenesis and acrosome identified. In addition, the mislocalisation of crucial chromatoid body components DDX4 (MVH) and UPF1 was also observed in round spermatids from patients harbouring TDRD6 variants. ScRNA-seq analysis of germ cells from a patient with TDRD6 variants revealed that TDRD6 regulates mRNA metabolism processes involved in spermatid differentiation and cytoplasmic translation. CONCLUSION: Our findings strongly suggest that TDRD6 plays a conserved role in spermiogenesis and confirms the causal relationship between TDRD6 variants and human OAT. Additionally, this study highlights the unfavourable ICSI outcomes in individuals with bi-allelic TDRD6 variants, providing insights for potential clinical treatment strategies.

18.
Sci Rep ; 14(1): 4477, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38396063

RESUMO

We conducted a systematic search across medical databases, including PubMed, Web of Science, EMBASE, and Cochrane Library, up to March 2023. A total of 1944 subjects or individuals from 17 studies were included in our final analysis. The correlation coefficient (r) between sKlotho and calcium was [0.14, (0.02, 0.26)], and a moderate heterogeneity was observed (I2 = 66%, P < 0.05). The correlation coefficient (r) between Klotho and serum phosphate was [- 0.21, (- 0.37, - 0.04)], with apparent heterogeneity (I2 = 84%, P < 0.05). The correlation coefficient (r) between sKlotho and parathyroid hormone and vascular calcification was [- 0.23,(- 0.29, - 0.17); - 0.15, (- 0.23, - 0.08)], with no significant heterogeneity among the studies. (I2 = 40%, P < 0.05; I2 = 30%, P < 0.05). A significant correlation exists between low sKlotho levels and an increased risk of CKD-MBD in patients with CKD. According to the findings, sKlotho may play a role in alleviating CKD-MBD by lowering phosphorus and parathyroid hormone levels, regulating calcium levels, and suppressing vascular calcification. As analysis showed that sKlotho has an important impact on the pathogenesis and progression of CKD-MBD in CKD patients. Nonetheless, further comprehensive and high-quality studies are needed to validate our conclusions.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica , Insuficiência Renal Crônica , Calcificação Vascular , Humanos , Cálcio , Hormônio Paratireóideo , Insuficiência Renal Crônica/complicações
19.
Nutrients ; 16(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38337739

RESUMO

OBJECTIVES: This study aims to examine the relationship between dietary inflammatory index (DII) and bone mineral density (BMD) changes among Chinese pregnant women, offering valuable insights for dietary guidance during pregnancy. METHODS: 289 pregnant women were enrolled in this cohort. Serum inflammatory factors and ultrasonic BMD were measured at the first, second, and the third trimesters. DII scores were calculated based on a semi-quantitative food frequency questionnaire (FFQ) and divided into tertiles. We compared the differences in inflammatory factors in serum across the tertiles of DII and changes in BMD at the second and third trimesters across the tertiles. RESULTS: The participants with higher DII scores had higher total energy intakes than those with lower DII scores. The serum level of interleukin-6 (IL-6) was significantly different across the tertiles of the DII. Women who had lower DII scores had higher T-scores and Z-scores in the BMD assessment. In the test of trends, after adjusting potential covariates, including educational level, physical activity, body mass index, and calcium, vitamin D, or multivitamin supplements, DII values were determined to be positively related to the maternal BMD lost. CONCLUSIONS: DII was positively associated with serum IL-6. Meanwhile, higher DII scores were associated with more bone mass loss in pregnant women. We recommend adhering to a lower-DII diet to preserve BMD during pregnancy.


Assuntos
Densidade Óssea , Gestantes , Humanos , Feminino , Gravidez , Estudos Prospectivos , Interleucina-6 , Dieta , Inflamação
20.
Exp Aging Res ; 50(2): 225-247, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38192191

RESUMO

Empathy, the ability to understand and respond to the experiences of others, is an important skill for maintaining good relationships throughout one's life. Previous research indicated that emotional empathy remained stable or even increased in older adults compared to younger adults, while cognitive empathy showed age-related deficits. Based on the selective engagement hypothesis, this deficit was not caused by a decline in cognitive functioning, but by a lack of willingness to judge the target person's emotions more precisely, that is, by a lack of interaction motivation. In order to provide more evidence on the causes of empathic aging in older adults, the current study investigated the influence of interaction motivation on empathy in older adults in an Eastern cultural context (China) based on the selective engagement hypothesis. This study used older adults and younger adults as subjects. Through two experiments, empathy was measured by the multiple empathy test (Experiment 1) and film tasks (Experiment 2); at the same time, use accountability instructions (Experiment 1), the age-related events (Experiment 2) to manipulate interaction motivation. The results showed that emotional empathy was significantly higher in older adults than in younger adults, regardless of whether interaction motivation was elicited. In terms of cognitive empathy, when there is no motivation, the cognitive empathy of older adults is significantly lower than that of younger adults. When the interaction motivation is stimulated, the cognitive empathy of older adults is no less than that of younger adults. This suggested that empathic aging in older adults was not a permanent decline in cognitive empathy, but rather a decline in interaction motivation, supporting the selective engagement hypothesis.


Assuntos
Empatia , Motivação , Humanos , Idoso , Envelhecimento , Emoções , Cognição
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