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1.
Andrology ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958226

RESUMO

BACKGROUND: Despite cryptorchidism being a common genital abnormality in male newborns with significant prevalence variations globally, there is a notable scarcity of epidemiological data on this condition in China. OBJECTIVE: This study aimed to delineate the prevalence pattern of cryptorchidism in Chinese population over the past 15 years using nationwide surveillance data. MATERIALS AND METHODS: Data from the China National Population-based Birth Defects Surveillance System (2007-2021) were analyzed to calculate the prevalence rates of cryptorchidism, stratified by birth year, maternal age, maternal residence, and geographic region. Adjusted prevalence rate ratios were computed using Poisson regression, while trends in prevalence and average annual percent change (AAPC) were assessed using the joinpoint regression model. RESULTS: During the study period, a total of 1,833 cases of cryptorchidism were identified among 2,565,964 full-term male births, resulting in prevalence rates of 7.14, 5.60, and 1.54 per 10,000 births for overall, isolated, and associated cryptorchidism, respectively. The overall prevalence increased from 3.86 to 11.20 per 10,000 births, with an AAPC of 7.9% (95% confidence interval: 5.5-11.0). Significant variations were observed across maternal age (< 20 years, 7.62/10,000; 20-24 years, 6.14/10,000; 25-29 years, 6.96/10,000; 30-34 years, 7.48/10,000; ≥35 years, 9.22/10,000), maternal residence (urban vs. rural, 10.99/10,000 vs. 2.86/10,000), and geographic region (eastern, 12.38/10,000; central, 2.36/10,000; western, 2.63/10,000). Approximately one-third of cryptorchidism cases were bilaterally, while two-thirds were unilateral. Commonly observed associated abnormalities included congenital hydrocele testis, as well as anomalies in the genital organs, circulatory system, and musculoskeletal system. CONCLUSION: Despite lower rates compared to other countries, the increasing trend in prevalence of cryptorchidism necessitates further investigation and intervention.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38963606

RESUMO

PURPOSE: To identify novel variants in ACTL9 and new phenotypes responsible for male infertility. METHODS: Genomic DNA was extracted from peripheral blood samples for whole-exome sequencing (WES). Computer-assisted sperm analysis (CASA) was used to test the motility of spermatozoa. The ultrastructure of flagella and the mitochondrial sheath were assessed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Immunostaining was used to validate the localization and expression of ACTL9 and ACTL7A. An Actl9-mutated mouse model was used to validate the phenotypes by CASA and TEM. RESULTS: We identified novel homozygous variants in ACTL9 in two independent Chinese families. Spermatozoa with ACTL9 mutations showed decreased CASA parameters and a higher proportion of spermatozoa with abnormal morphology, exhibiting coiled flagella and a thickened midpiece. The spermatozoa were characterized by chaotic or irregular '9+2' structures and irregular mitochondrial sheath arrangements in the flagellum. Actl9 knock-in mice also showed abnormal CASA parameters and irregular '9+2' structures in flagella. CONCLUSIONS: Our study expands the mutation spectrum and phenotypic spectrum of ACTL9.

3.
Opt Lett ; 49(13): 3701-3704, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38950246

RESUMO

We presented the first, to our knowledge, demonstration of an ultraviolet (UV) laser at 223.8 nm by six-harmonic generation of an electro-optic Q-switched cavity dumping 1342 nm Nd:YVO4 laser. It offers high power, constant short pulse duration, and adjustable pulse repetition rate. The pulse duration is independent of the pump power and repetition rate compared to classical Q-switched oscillators. The output efficiency of the UV laser is optimized by adjusting the focusing lens. With the incident pump power of 30 W, an maximum average output power of 249 mW was obtained at 13 kHz. The pulse width maintained 3.4-3.5 ns from 5 to 20 kHz. The maximum pulse energy of 28.1 µJ was obtained at 5 kHz, and the corresponding peak power was up to 8.1 kW.

5.
Ecotoxicol Environ Saf ; 281: 116663, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964059

RESUMO

Biological characteristics of pregnant women during early pregnancy make them susceptible to both poor sleep quality and metal/metalloid exposure. However, the effects of metal(loid) exposure on sleep quality in pregnant women remain unknown and unexplored. We aimed to examine the relationship between exposure to a mixture of metal(loid)s and pregnant women's sleep quality during early pregnancy. We recruited 493 pregnant women in the first trimester from prenatal clinics in Jinan, Shandong Province, China, and collected their spot urine samples. All urine specimens were assessed for eight metal(loid)s: arsenic (As), cadmium (Cd), iron (Fe), zinc (Zn), molybdenum (Mo), lead (Pb), selenium (Se), and mercury (Hg). We used the Pittsburgh Sleep Quality Index (PSQI) to assess sleep quality. Linear regression, logistic regression, generalized additive models (GAMs), quantile g-computation, and Bayesian kernel machine regression (BKMR) were applied to investigate the relationships between metal(loid) exposure and sleep quality. The results from single metal(loid) models, quantile g-computation models, and BKMR models consistently suggested that Fe was positively related to women's sleep quality. Moreover, in the quantile g-computation models, As was the most critical contributor to the negative effects of the metal(loid) mixture on sleep quality. In addition, we found significant As by Fe interaction for scores of PSQI and habitual sleep efficiency, Pb by Fe interaction for PSQI and sleep latency, and Hg by Fe interaction for PSQI, suggesting the interactive effects of As and Fe, Pb and Fe, Hg and Fe on sleep quality and specific sleep components. Our study provided the first-hand evidence of the effects of metal(loid) exposure on pregnant women's sleep quality. The underlying mechanisms need to be explored in the future.

6.
Gene ; 927: 148748, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38969245

RESUMO

Biomineralization processes in bivalves, particularly the initial production of molecular components (such as matrix deposition and calcification) in the early stages of shell development are highly complex and well-organized. This study investigated the temporal dynamics of organic matrix and calcium carbonate (CaCO3) deposition in Pacific oysters (Crassostrea gigas) across various development stages. The shell-field initiated matrix secretion during the gastrula stage. Subsequent larval development triggered central shell-field calcification, accompanied by expansion of the calcium ring from its interior to the periphery. Notably, the expression patterns of CgTyrp-2 and CgTyr closely correlated with matrix deposition and calcification during early developmental stages, with peak expression occurring in oyster's gastrula and D-veliger stages. Subsequently, the CRISPR/Cas9 system was utilized to knock out CgTyrp-2 and CgTyr with more distinct phenotypic alterations observed when both genes were concurrently knocked out. The relative gene expression was analyzed post-knockout, indicating that the knockout of CgTyr or CgTyrp-2 led to reduced expression of CgChs1, along with increased expression of CgChit4. Furthermore, when dual-sgRNAs were employed to knockout CgTyrp-2, a large deletion (2 kb) within the CgTyrp-2 gene was identified. In summary, early shell formation in C. gigas is the result of a complex interplay of multiple molecular components with CgTyrp-2 and CgTyr playing key roles in regulating CaCO3 deposition.

7.
aBIOTECH ; 5(2): 225-230, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38974856

RESUMO

The widely used clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) system is thought to have evolved from IS200/IS605 transposons. TnpB proteins, encoded by one type of IS200/IS605 transposon, are considered to be the evolutionary ancestors of Cas12 nucleases, which have been engineered to function as RNA-guided DNA endonucleases for genome editing in bacteria and human cells. TnpB nucleases, which are smaller than Cas nucleases, have been engineered for use in genome editing in animal systems, but the feasibility of this approach in plants remained unknown. Here, we obtained stably transformed genome-edited mutants in rice (Oryza sativa) by adapting three recently identified TnpB genome editing vectors, encoding distinct TnpB nucleases (ISAam1, ISDra2, and ISYmu1), for use in plants, demonstrating that the hypercompact TnpB proteins can effectively edit plant genomes. ISDra2 and ISYmu1 precisely edited their target sequences, with no off-target mutations detected, showing that TnpB transposon nucleases are suitable for development into a new genome editing tool for plants. Future modifications improving the genome-editing efficiency of the TnpB system will facilitate plant functional studies and breeding programs. Supplementary Information: The online version contains supplementary material available at 10.1007/s42994-024-00172-6.

8.
Int Immunopharmacol ; 138: 112564, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943978

RESUMO

BACKGROUND: The effect of preoperative natural killer (NK) cell abnormalities on postoperative pulmonary complications (PPCs) after thoracoscopic radical resection of lung cancer is still unclear. The main purpose of this study was to investigate the relationship between the preoperative NK cell ratio and PPCs. METHODS: The patients who underwent thoracoscopic radical resection for lung cancer were divided into a normal group and an abnormal group according to whether the proportion of preoperative NK cells was within the reference range. The main outcome was the incidence of PPCs during postoperative hospitalization. The demographic and perioperative data were collected. Propensity score matching was used to exclude systematic bias. Univariate logistic regression was used to test the relationship between the preoperative NK cell ratio and the incidence of PPCs. The restrictive cubic spline curve was used to analyze the dose-effect relationship between the preoperative NK cell ratio and the incidence of PPCs. RESULTS: A total of 4161 patients were included. After establishing a matching cohort, 910 patients were included in the statistical analysis. The incidence of PPCs in the abnormal group was greater than that in the normal group (55.2% vs. 31.6%). The incidence of PPCs first decreased and then increased with increasing NK cell ratio. The proportion of patients with Grade 3 or higher PPCs in the normal group was lower than that in the abnormal group [108 (23.7%) vs. 223 (49%)]. The indwelling time of the thoracic drainage tube in the abnormal group was longer than that in the normal group [3 (3, 4) vs. 3 (3, 5)]. A preoperative abnormal NK cell ratio constituted a risk factor for PPCs in each subgroup. CONCLUSION: Lung cancer patients with an abnormal proportion of peripheral blood NK cells before surgery were more likely to develop PPCs, their disease degree was more severe, and they had a prolonged duration of chest tube indwelling. Compared with those with abnormally high NK cell ratios, those with abnormally low NK cell ratios had more pronounced PPCs.

9.
BMC Cancer ; 24(1): 778, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943058

RESUMO

BACKGROUND: Metal-regulatory transcription factor 1 (MTF1), a conserved metal-binding transcription factor in eukaryotes, regulates the proliferation of cancer cells by activating downstream target genes and then participates in the formation and progression of tumors, including lung cancer (LC). The expression level of MTF1 is down-regulated in LC, and high expression of MTF1 is associated with a good prognosis of LC. However, the association between MTF1 polymorphism and LC risk has not been explored. METHODS: The genotyping of MTF1 Single nucleotide polymorphisms (SNPs) including rs473279, rs28411034, rs28411352, and rs3748682 was identified by the Agena MassARRAY system among 670 healthy controls and 670 patients with LC. The odds ratio (OR) and 95% confidence intervals (CI) were calculated by logistics regression to assess the association of these SNPs with LC risk. RESULTS: MTF1 rs28411034 (OR 1.22, 95% CI 1.03-1.45, p = 0.024) and rs3748682 (OR 1.24, 95% CI 1.04-1.47, p = 0.014) were associated with higher LC susceptibility overall. Moreover, the effect of rs28411034 and rs3748682 on LC susceptibility was observed in males, subjects with body mass index (BMI) ≥ 24 kg/m2, smokers, drinkers, and patients with lung squamous carcinoma (OR and 95% CI > 1, p < 0.05). Besides, rs28411352 (OR 0.73, 95% CI 0.55-0.97, p = 0.028,) showed protective effect for reduced LC risk in drinkers. CONCLUSIONS: We were first who reported that rs28411034 and rs3748682 tended to be relevant to increased LC susceptibility among the Chinese Han population. These results of this study could help to recognize the pathogenic mechanisms of the MTF1 gene in LC progress.


Assuntos
Povo Asiático , Proteínas de Ligação a DNA , Predisposição Genética para Doença , Neoplasias Pulmonares , Polimorfismo de Nucleotídeo Único , Fator MTF-1 de Transcrição , Fatores de Transcrição , Humanos , Neoplasias Pulmonares/genética , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Transcrição/genética , Povo Asiático/genética , Proteínas de Ligação a DNA/genética , Estudos de Casos e Controles , China/epidemiologia , Idoso , Genótipo , Fatores de Risco , População do Leste Asiático
10.
Mol Med ; 30(1): 98, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943069

RESUMO

BACKGROUND: L-theanine is a unique non-protein amino acid in tea that is widely used as a safe food additive. We investigated the cardioprotective effects and mechanisms of L-theanine in myocardial ischemia-reperfusion injury (MIRI). METHODS: The cardioprotective effects and mechanisms of L-theanine and the role of Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling were investigated in MIRI mice using measures of cardiac function, oxidative stress, and apoptosis. RESULTS: Administration of L-theanine (10 mg/kg, once daily) suppressed the MIRI-induced increase in infarct size and serum creatine kinase and lactate dehydrogenase levels, as well as MIRI-induced cardiac apoptosis, as evidenced by an increase in Bcl-2 expression and a decrease in Bax/caspase-3 expression. Administration of L-theanine also decreased the levels of parameters reflecting oxidative stress, such as dihydroethidium, malondialdehyde, and nitric oxide, and increased the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD) in ischemic heart tissue. Further analysis showed that L-theanine administration suppressed the MIRI-induced decrease of phospho-JAK2 and phospho-STAT3 in ischemic heart tissue. Inhibition of JAK2 by AG490 (5 mg/kg, once daily) abolished the cardioprotective effect of L-theanine, suggesting that the JAK2/STAT3 signaling pathway may play an essential role in mediating the anti-I/R effect of L-theanine. CONCLUSIONS: L-theanine administration suppresses cellular apoptosis and oxidative stress in part via the JAK2/STAT3 signaling pathway, thereby attenuating MIRI-induced cardiac injury. L-theanine could be developed as a potential drug to alleviate cardiac damage in MIRI.


Assuntos
Apoptose , Glutamatos , Janus Quinase 2 , Traumatismo por Reperfusão Miocárdica , Estresse Oxidativo , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/etiologia , Apoptose/efeitos dos fármacos , Glutamatos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Masculino , Camundongos , Cardiotônicos/farmacologia , Cardiotônicos/uso terapêutico
11.
Genes (Basel) ; 15(6)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38927622

RESUMO

BACKGROUND: Malaria results in more than 550,000 deaths each year due to drug resistance in the most lethal Plasmodium (P.) species P. falciparum. A full P. falciparum genome was published in 2002, yet 44.6% of its genes have unknown functions. Improving the functional annotation of genes is important for identifying drug targets and understanding the evolution of drug resistance. RESULTS: Genes function by interacting with one another. So, analyzing gene co-expression networks can enhance functional annotations and prioritize genes for wet lab validation. Earlier efforts to build gene co-expression networks in P. falciparum have been limited to a single network inference method or gaining biological understanding for only a single gene and its interacting partners. Here, we explore multiple inference methods and aim to systematically predict functional annotations for all P. falciparum genes. We evaluate each inferred network based on how well it predicts existing gene-Gene Ontology (GO) term annotations using network clustering and leave-one-out crossvalidation. We assess overlaps of the different networks' edges (gene co-expression relationships), as well as predicted functional knowledge. The networks' edges are overall complementary: 47-85% of all edges are unique to each network. In terms of the accuracy of predicting gene functional annotations, all networks yielded relatively high precision (as high as 87% for the network inferred using mutual information), but the highest recall reached was below 15%. All networks having low recall means that none of them capture a large amount of all existing gene-GO term annotations. In fact, their annotation predictions are highly complementary, with the largest pairwise overlap of only 27%. We provide ranked lists of inferred gene-gene interactions and predicted gene-GO term annotations for future use and wet lab validation by the malaria community. CONCLUSIONS: The different networks seem to capture different aspects of the P. falciparum biology in terms of both inferred interactions and predicted gene functional annotations. Thus, relying on a single network inference method should be avoided when possible. SUPPLEMENTARY DATA: Attached.


Assuntos
Redes Reguladoras de Genes , Plasmodium falciparum , Plasmodium falciparum/genética , Malária Falciparum/parasitologia , Malária Falciparum/genética , Humanos , Ontologia Genética , Anotação de Sequência Molecular/métodos , Proteínas de Protozoários/genética
12.
J Biotechnol ; 391: 106-116, 2024 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-38871028

RESUMO

Icaritin, a hydrolysate from total flavonoids of Epimedii (TFE), which has better anti-hepatoma activity than its glycosylated form. In this work, immobilized enzymes 4LP-Tpebgl3@Na-Y and DtRha@ES-107 were used to hydrolyze TFE to prepare icaritin. Five different hydrophobic deep eutectic solvents (HDES) were prepared and the most ideal HDES was successfully selected, which was composed of dodecyl alcohol and thymol with the molar ratio of 2:1. The relative enzyme activity of 4LP-Tpebgl3@Na-Y and DtRha@ES-107 was about 102.4 % and 112.5 %, respectively. In addition, the thermal and binding stability of 4LP-Tpebgl3@Na-Y and DtRha@ES-107 in HDES was not affected negatively. In the biphasic system composed of 50 % (v/v) HDES and Na2HPO4-citric acid buffer (50 mM, pH 5.5), 4LP-Tpebgl3@Na-Y (1.0 U/mL) and TFE (1 g/L) were reacted at 80 °C for 1 h, and then reacted with DtRha@ES-107 (20 U/mL) at 80 °C for 2 h. Finally, TFE was completely converted to 301.8 mg/L icaritin (0.82 mM). After 10 cycles, 4LP-Tpebgl3@Na-Y/DtRha@ES-107 still maintained 84.1 % original activity. In this study, we developed an efficient methodology for icaritin preparation through the integration of enzymatic catalysis and adsorption separation, presenting a viable approach for large-scale, cost-effective production of icaritin.


Assuntos
Biotransformação , Enzimas Imobilizadas , Flavonoides , Interações Hidrofóbicas e Hidrofílicas , Flavonoides/metabolismo , Flavonoides/química , Enzimas Imobilizadas/metabolismo , Enzimas Imobilizadas/química , Solventes Eutéticos Profundos/química , Solventes Eutéticos Profundos/metabolismo , Epimedium/química , Epimedium/metabolismo , Hidrólise , Solventes/química
13.
BMC Cancer ; 24(1): 758, 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38914961

RESUMO

BACKGROUND: Colon cancer (CC) is a malignancy associated with significant morbidity and mortality within the gastrointestinal tract. Recurrence and metastasis are the main factors affecting the prognosis of CC patients undergoing radical surgery; consequently, we attempted to determine the impact of immunity-related genes. RESULT: We constructed a CC risk model based on ZG16, MPC1, RBM47, SMOX, CPM and DNASE1L3. Consistently, we found that a significant association was found between the expression of most characteristic genes and tumor mutation burden (TMB), microsatellite instability (MSI) and neoantigen (NEO). Additionally, a notable decrease in RBM47 expression was observed in CC tissues compared with that in normal tissues. Moreover, RBM47 expression was correlated with clinicopathological characteristics and improved disease-free survival (DFS) and overall survival (OS) among patients with CC. Lastly, immunohistochemistry and co-immunofluorescence staining revealed a clear positive correlation between RBM47 and CXCL13 in mature tertiary lymphoid structures (TLS) region. CONCLUSION: We conclude that RBM47 was identified as a prognostic-related gene, which was of great significance to the prognosis evaluation of patients with CC and was correlated with CXCL13 in the TLS region.


Assuntos
Biomarcadores Tumorais , Neoplasias do Colo , Instabilidade de Microssatélites , Humanos , Neoplasias do Colo/genética , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Prognóstico , Masculino , Feminino , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Idoso , Mutação , Regulação Neoplásica da Expressão Gênica , Intervalo Livre de Doença
14.
Emerg Microbes Infect ; : 2373314, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922326

RESUMO

The proportion of human isolates with reduced neuraminidase inhibitors (NAIs) susceptibility in highly pathogenic avian influenza (HPAI) H7N9 virus was as high as 13%. These drug-resistant strains showed good replication capacity without serious loss of fitness. At the presence of oseltamivir, R229I substitution were found in HA1 region of the HPAI H7N9 virus before NA R292 K appeared. HPAI H7N9 or H7N9/PR8 recombinant viruses were developed to study whether HA R229I could increase the fitness of the H7N9 virus bearing NA 292 K. Replication efficiency was assessed in MDCK or A549 cells. Neuraminidase enzyme activity and receptor-binding ability were analyzed. The pathogenicity in C57 mice was evaluated. Antigenicity analysis was conducted through a two-way HI test, in which the antiserum was obtained from immunized ferrets. Transcriptomic analysis of MDCK infected with HPAI H7N9 24hpi was done. It turned out that HA R229I substitution from oseltamivir induction in HA1 region increased 1)replication ability in MDCK(P < 0.05) and A549(P < 0.05), 2)neuraminidase enzyme activity, 3)binding ability to both α2,3 and α2,6 receptor, 4)pathogenicity to mice(more weight loss; shorter mean survival day; viral titer in respiratory tract, P < 0.05; Pathological changes in pneumonia), 5) transcriptome response of MDCK, of the H7N9 virus bearing NA 292 K. Besides, HA R229I substitution changed the antigenicity of H7N9/PR8 virus (>4-fold difference of HI titer). It indicated that through the fine-tuning of the HA-NA balance, R229I increased the fitness and change the antigenicity of a H7N9 virus bearing NA 292 K. Public health attention of this mechanism needs to be drawn.

15.
BMC Urol ; 24(1): 123, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867229

RESUMO

BACKGROUND: Male infertility has become a global health problem, and genetic factors are one of the essential causes. Y chromosome microdeletion is the leading genetic factor cause of male infertility. The objective of this study is to investigate the correlation between male infertility and Y chromosome microdeletions in Hainan, the sole tropical island province of China. METHODS: We analyzed the semen of 897 infertile men from Hainan in this study. Semen analysis was measured according to WHO criteria by professionals at the Department of Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, where samples were collected. Y chromosome AZF microdeletions were confirmed by detecting six STS markers using multiple polymerase chain reactions on peripheral blood DNA. The levels of reproductive hormones, including FSH, LH, PRL, T, and E2, were quantified using the enzyme-linked immunosorbent assay (ELISA). RESULTS: The incidence of Y chromosome microdeletion in Hainan infertile men was 7.13%. The occurrence rate of Y chromosome microdeletion was 6.69% (34/508) in the oligozoospermia group and 7.71% (30/389) in the azoospermia group. The deletion of various types in the AZF subregion was observed in the group with azoospermia, whereas no AZFb deletion was detected in the oligozoospermia group. Among all patients with microdeletions, the deletion rate of the AZFc region was the higher at 68.75% (44 out of 64), followed by a deletion rate of 6.25% (4 out of 64) for the AZFa region and a deletion rate of 4.69% (3 out of 64) for the AZFb region. The deletion rate of the AZFa region was significantly higher in patients with azoospermia than in patients with oligozoospermia (0.51% vs. 0.39%, p < 0.001). In comparison, the deletion rate of the AZFc region was significantly higher in patients with oligozoospermia (3.08% vs. 6.30%, p < 0.001). Additionally, the AZFb + c subregion association deletion was observed in the highest proportion among all patients (0.89%, 8/897), followed by AZFa + b + c deletion (0.56%, 5/897), and exclusively occurred in patients with azoospermia. Hormone analysis revealed FSH (21.63 ± 2.01 U/L vs. 10.15 ± 0.96 U/L, p = 0.001), LH (8.96 ± 0.90 U/L vs. 4.58 ± 0.42 U/L, p < 0.001) and PRL (263.45 ± 21.84 mIU/L vs. 170.76 ± 17.10 mIU/L, p = 0.002) were significantly increased in azoospermia patients with microdeletions. Still, P and E2 levels were not significantly different between the two groups. CONCLUSIONS: The incidence of AZF microdeletion can reach 7.13% in infertile men in Hainan province, and the deletion of the AZFc subregion is the highest. Although the Y chromosome microdeletion rate is distinct in different regions or populations, the regions mentioned above of the Y chromosome may serve an indispensable role in regulating spermatogenesis. The analysis of Y chromosome microdeletion plays a crucial role in the clinical assessment and diagnosis of male infertility.


Assuntos
Deleção Cromossômica , Cromossomos Humanos Y , Infertilidade Masculina , Técnicas de Reprodução Assistida , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual , Humanos , Masculino , Infertilidade Masculina/genética , Infertilidade Masculina/sangue , Infertilidade Masculina/epidemiologia , China/epidemiologia , Adulto , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/sangue , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/epidemiologia , Hormônio Luteinizante/sangue , Hormônio Foliculoestimulante/sangue , Azoospermia/genética , Azoospermia/sangue , Prolactina/sangue , Oligospermia/genética , Oligospermia/sangue , Testosterona/sangue , Estradiol/sangue , Análise do Sêmen
16.
J Control Release ; 371: 324-337, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38823584

RESUMO

There is an urgent clinical need to develop nerve-blocking agents capable of inducing long duration sensory block without muscle weakness or paralysis to treat post-operative and chronic pain conditions. Here, we report a galacturonic acid-capsaicin (GalA-CAP) prodrug as an effective nociceptive-selective axon blocking agent. Capsaicin selectively acts on nociceptive signaling without motor nerve blockade or disruption of proprioception and touch sensation, and the galacturonic acid moiety enhance prodrug permeability across the restrictive peripheral nerve barriers (PNBs) via carrier-mediated transport by the facilitative glucose transporters (GLUTs). In addition, following prodrug transport across PNBs, the inactive prodrug is converted to active capsaicin through linker hydrolysis, leading to sustained drug release. A single injection of GalA-CAP prodrug at the sciatic nerves of rats led to nociceptive-selective nerve blockade lasting for 234 ± 37 h, which is a sufficient duration to address the most intense period of postsurgical pain. Furthermore, the prodrug markedly mitigated capsaicin-associated side effects, leading to a notable decrease in systemic toxicity, benign local tissue reactions, and diminished burning and irritant effects.


Assuntos
Capsaicina , Bloqueio Nervoso , Pró-Fármacos , Ratos Sprague-Dawley , Nervo Isquiático , Pró-Fármacos/administração & dosagem , Animais , Capsaicina/administração & dosagem , Capsaicina/análogos & derivados , Masculino , Nervo Isquiático/efeitos dos fármacos , Bloqueio Nervoso/métodos , Ratos , Analgésicos/administração & dosagem , Analgésicos/farmacologia
17.
Microbiol Spectr ; : e0429223, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38916349

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an RNA virus that undergoes rapid mutation. Based on viral whole genome sequencing analysis in Hebei Province, China, we identified several essential single nucleotide variants (SNVs) on primer-probe regions accumulating within some Omicron variants' genomes. In this study, we focused on three SNVs, C28290T, T28297C, and C28311T emerging on 2019-nCoV-N1 (CDC-N1) primer-probe regions, recommended by CDC in 2020, and two SNVs, C26270T, A26275G emerging on E (Charité-E) primer-probe regions recommended by Charité, Germany. Our findings revealed that the presence of one or two SNVs in the primer or probe region affected the sensitivity of reverse transcription-quantitative polymerase chain reaction and droplet digital PCR to varying extents. This discovery underscores the importance of continuously monitoring the whole genome sequences of SARS-CoV-2 variants, especially the primer-probe targeting regions, and correspondingly updating commercial test kits or recommended primer-probe sequence sets. IMPORTANCE: The emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has resulted in a growing number of mutations in its genome, presenting new challenges for the diagnosis of SARS-CoV-2 using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and droplet digital PCR (RT-ddPCR) methods. There is an urgent need to develop refined methods for modifying primers and probes to improve the detection of these emerging variants. In this study, our focus was on the SNVs that have emerged in the CDC-N1 and Charité-E primer-probe regions. Our research has confirmed that the presence of these SNVs in the primer or probe region can significantly affect the results of coronavirus disease 2019 tests. we have developed and validated a modified detection method that can provide higher sensitivity and specificity. This study emphasizes the importance of refining the primer-probe sets to ensure the diagnostic accuracy of RT-qPCR and RT-ddPCR detection.

18.
Spectrochim Acta A Mol Biomol Spectrosc ; 320: 124613, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-38865887

RESUMO

As a crucial endogenous reactive oxygen species, hypochlorous acid (HClO) plays an indispensable role in numerous physiological and pathological processes. Additionally, it serves as a biomarker closely associated with inflammation and liver injury. The utilization of near-infrared fluorescence probes has surged in recent years for live biological imaging, owing to their minimal tissue damage and potent tissue penetration capabilities. In this work, a novel near-infrared fluorescence probe MB-HPD was synthesized to sensitively detect HClO. Probe MB-HPD exhibits remarkable selectivity, high sensitivity (14.3 nM), and rapid response towards HClO (20 s). Probe MB-HPD has demonstrated successful application in the imaging of HClO within cells and zebrafish. Remarkably, it has proven to be effective for detecting HClO within environmental samples, as well as imaging HClO in mice models of arthritis and APAP-induced liver injury. These findings indicate the broad applicability of probe MB-HPD, offering a promising avenue for designing highly selective near-infrared fluorescence probes suitable for real-time HClO monitoring.


Assuntos
Monitoramento Ambiental , Corantes Fluorescentes , Ácido Hipocloroso , Peixe-Zebra , Ácido Hipocloroso/análise , Corantes Fluorescentes/química , Animais , Camundongos , Humanos , Monitoramento Ambiental/métodos , Colorimetria/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Imagem Óptica/métodos
19.
Neuroimage ; 297: 120707, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942102

RESUMO

Under resource distribution context, individuals have a strong aversion to unfair treatment not only toward themselves but also toward others. However, there is no clear consensus regarding the commonality and distinction between these two types of unfairness. Moreover, many neuroimaging studies have investigated how people evaluate and respond to unfairness in the abovementioned two contexts, but the consistency of the results remains to be investigated. To resolve these two issues, we sought to summarize existing findings regarding unfairness to self and others and to further elucidate the neural underpinnings related to distinguishing evaluation and response processes through meta-analyses of previous neuroimaging studies. Our results indicated that both types of unfairness consistently activate the affective and conflict-related anterior insula (AI) and dorsal anterior cingulate cortex/supplementary motor area (dACC/SMA), but the activations related to unfairness to self appeared stronger than those related to others, suggesting that individuals had negative reactions to both unfairness and a greater aversive response toward unfairness to self. During the evaluation process, unfairness to self activated the bilateral AI, dACC, and right dorsolateral prefrontal cortex (DLPFC), regions associated with unfairness aversion, conflict, and cognitive control, indicating reactive, emotional and automatic responses. In contrast, unfairness to others activated areas associated with theory of mind, the inferior parietal lobule and temporoparietal junction (IPL-TPJ), suggesting that making rational judgments from the perspective of others was needed. During the response, unfairness to self activated the affective-related left AI and striatum, whereas unfairness to others activated cognitive control areas, the left DLPFC and the thalamus. This indicated that the former maintained the traits of automaticity and emotionality, whereas the latter necessitated cognitive control. These findings provide a fine-grained description of the common and distinct neurocognitive mechanisms underlying unfairness to self and unfairness to others. Overall, this study not only validates the inequity aversion model but also provides direct evidence of neural mechanisms for neurobiological models of fairness.

20.
J Perianesth Nurs ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38842952

RESUMO

PURPOSE: This study aimed to determine the effect of a forced-air warming blanket placed on different body parts on the core temperature of patients undergoing elective open abdominal surgery. DESIGN: Prospective, single-center, randomized, controlled, single-blind trial. METHODS: A total of 537 patients who underwent open abdominal surgery were randomized into groups A, B, and C and provided with different forced-air warming blankets. Group A was given an upper body blanket, group B a lower body blanket, and group C an underbody blanket. The incidence of intraoperative hypothermia, the time maintaining the core temperature over 36 â„ƒ before hypothermia, the duration of hypothermia, the rewarming rate, and relevant complications were compared among three groups. FINDINGS: Intraoperative hypothermia occurred in 51.4% of patients in group B, 37.6% of patients in group A, and 34.1% of patients in group C (P = .002). Maintaining the core temperature above 36 â„ƒ was longer before hypothermia in groups A and C (log-rank P = .006). In groups A and C, the duration of hypothermia was shorter, the rewarming rate was higher, and the incidence of shivering and postoperative nausea and vomiting were lower, compared to group B. CONCLUSIONS: In patients undergoing elective open abdominal surgery, a forced-air warming blanket on the upper body part or underbody area decreased intraoperative hypothermia, prolonged the time to maintain the core temperature above 36 â„ƒ before hypothermia, and could better prevent further hypothermia when the core temperature had decreased below 36 â„ƒ. In addition, it was significantly superior in reducing shivering and postoperative nausea and vomiting in the postanesthesia care unit.

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