Histone deacetylase as emerging pharmacological therapeutic target for neuropathic pain: From epigenetic to selective drugs.

BACKGROUND: Neuropathic pain remains a formidable challenge for modern medicine. The first-line pharmacological therapies exhibit limited efficacy and unfavorable side effect profiles, highlighting an unmet need for effective therapeutic medications. The past decades have witnessed an explosion in efforts to translate epigenetic concepts into pain therapy and shed light on epigenetics as a promising avenue for pain research. Recently, the aberrant activity of histone deacetylase (HDAC) has emerged as a key mechanism contributing to the development and maintenance of neuropathic pain. AIMS: In this review, we highlight the distinctive role of specific HDAC subtypes in a cell-specific manner in pain nociception, and outline the recent experimental evidence supporting the therapeutic potential of HDACi in neuropathic pain. METHODS: We have summarized studies of HDAC in neuropathic pain in Pubmed. RESULTS: HDACs, widely distributed in the neuronal and non-neuronal cells of the dorsal root ganglion and spinal cord, regulate gene expression by deacetylation of histone or non-histone proteins and involving in increased neuronal excitability and neuroinflammation, thus promoting peripheral and central sensitization. Importantly, pharmacological manipulation of aberrant acetylation using HDAC-targeted inhibitors (HDACi) has shown promising pain-relieving properties in various preclinical models of neuropathic pain. Yet, many of which exhibit low-specificity that may induce off-target toxicities, underscoring the necessity for the development of isoform-selective HDACi in pain management. CONCLUSIONS: Abnormally elevated HDACs promote neuronal excitability and neuroinflammation by epigenetically modulating pivotal gene expression in neuronal and immune cells, contributing to peripheral and central sensitization in the progression of neuropathic pain, and HDACi showed significant efficacy and great potential for alleviating neuropathic pain.

Short-homology-mediated PCR-based method for gene introduction in the fission yeast Schizosaccharomyces pombe.

Schizosaccharomyces pombe is a commonly utilized model organism for studying various aspects of eukaryotic cell physiology. One reason for its widespread use as an experimental system is the ease of genetic manipulations, leveraging the natural homology-targeted repair mechanism to accurately modify the genome. We conducted a study to assess the feasibility and efficiency of directly introducing exogenous genes into the fission yeast S. pombe using Polymerase Chain Reaction (PCR) with short-homology flanking sequences. Specifically, we amplified the NatMX6 gene (which provides resistance to nourseothricin) using PCR with oligonucleotides that had short flanking regions of 20 bp, 40 bp, 60 bp and 80 bp to the target gene. By using this purified PCR product, we successfully introduced the NatMX6 gene at position 171 385 on chromosome III in S. pombe. We have made a simple modification to the transformation procedure, resulting in a significant increase in transformation efficiency by at least 5-fold. The success rate of gene integration at the target position varied between 20% and 50% depending on the length of the flanking regions. Additionally, we discovered that the addition of dimethyl sulfoxide and boiled carrier DNA increased the number of transformants by ~60- and 3-fold, respectively. Furthermore, we found that the removal of the pku70+ gene improved the transformation efficiency to ~5% and reduced the formation of small background colonies. Overall, our results demonstrate that with this modified method, even very short stretches of homologous regions (as short as 20 bp) can be used to effectively target genes at a high frequency in S. pombe. This finding greatly facilitates the introduction of exogenous genes in this organism.

Association of healthy lifestyle score with control of hypertension among treated and untreated hypertensive patients: a large cross-sectional study.

Background: Hypertension stands as the leading single contributor to the worldwide burden of mortality and disability. Limited evidence exists regarding the association between the combined healthy lifestyle score (HLS) and hypertension control in both treated and untreated hypertensive individuals. Therefore, we aimed to investigate the association between HLS and hypertension control among adults with treated and untreated hypertension. Methods: This cross-sectional study, including 311,994 hypertension patients, was conducted in Guangzhou using data from the National Basic Public Health Services Projects in China. The HLS was defined based on five low-risk lifestyle factors: healthy dietary habits, active physical activity, normal body mass index, never smoking, and no alcohol consumption. Controlled blood pressure was defined as systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg. A multivariable logistic regression model was used to assess the association between HLS and hypertension control after adjusting for various confounders. Results: The HLS demonstrated an inverse association with hypertension control among hypertensive patients. In comparison to the low HLS group (scored 0-2), the adjusted odds ratios (95% confidence intervals) for hypertension were 0.76 (0.74, 0.78), 0.59 (0.57, 0.60), and 0.48 (0.46, 0.49) for the HLS groups scoring 3, 4, and 5, respectively (Ptrend < 0.001). Notably, an interaction was observed between HLS and antihypertensive medication in relation to hypertension control (Pinteraction < 0.001). When comparing the highest HLS (scored 5) with the lowest HLS (scored 0-2), adjusted odds ratios (95% confidence intervals) were 0.50 (0.48, 0.52, Ptrend < 0.001) among individuals who self-reported using antihypertensive medication and 0.41 (0.38, 0.44, Ptrend < 0.001) among those not using such medication. Hypertensive patients adhering to a healthy lifestyle without medication exhibited better blood pressure management than those using medication while following a healthy lifestyle. Conclusion: HLS was associated with a reduced risk of uncontrolled blood pressure.

Association of adiposity indicators with cardiometabolic multimorbidity risk in hypertensive patients: a large cross-sectional study.

Background: Cardiometabolic multimorbidity (CMM) has emerged as a prominent public health concern. Hypertensive patients are prone to develop comorbidities. Moreover, the accumulation of visceral adipose tissue is the main cause for the development of cardiometabolic diseases. The cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese visceral adiposity index (CVAI) not only assess adipose tissue mass but also reflect adipose tissue dysfunction. So far, no study has been reported to evaluate the association of CMI, LAP, VAI, and CVAI with CMM risk in hypertensive patients. Therefore, this study aimed to assess the association between these adiposity indicators and the risk of CMM among Chinese hypertensive patients. Methods: In this cross-sectional study, a total of 229,287 hypertensive patients aged 35 years and older were included from the National Basic Public Health Service Project. All participants underwent a face-to-face questionnaire survey, physical examination, and the collection of fasting venous blood samples. Multivariable logistic regression models were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic curve was utilized to evaluate the identification ability for CMM. Results: After adjusting for confounders, each 1-standard deviation increase in CMI, LAP, VAI, and CVAI was associated with a 14%, 8%, 12%, and 54% increased risk of CMM, respectively. When comparing the highest quartile of these indicators with the lowest quartile, individuals in the highest quartile of CMM, LAP, VAI, and CVAI had a 1.39-fold (95% CI 1.30, 1.48), 1.28-fold (95% CI 1.19, 1.37), 1.37-fold (95% CI 1.29, 1.46), and 2.56-fold (95% CI 2.34, 2.79) increased risk of CMM after adjusting for potential confounders. Notably, a nonlinear association was observed for CMI, LAP, and VAI with the risk of CMM (all P nonlinearity < 0.001). CVAI exhibited the highest area under the receiver operating characteristic curve (AUC) among all the included adiposity indices in this analysis. Conclusion: This study indicated the significant positive association of CMI, LAP, VAI, and CVAI with the risk of CMM in hypertensive patients. Among these indicators, CVAI demonstrated the most robust performance in predicting CMM risk and may serve as a valuable tool for identifying CMM risk in Chinese hypertensive patients.

Physiological Investigation and Transcriptome Analysis Reveals the Mechanisms of Setaria italica's Yield Formation under Heat Stress.

Setaria italica is an important crop in China that plays a vital role in the Chinese dietary structure. In the last several decades, high temperature has become the most severe climate issue in the world, which causes great harm to the yield and quality formation of millet. In this study, two main cultivated varieties (ZG2 and AI88) were used to explore the photosynthesis and yield index of the whole plant under heat stress. Results implied that photosynthesis was not inhibited during the heat stress, and that the imbalance in sugar transport between different tissues may be the main factor that affects yield formation. In addition, the expression levels of seven SiSUT and twenty-four SiSWEET members were explored. Sugar transporters were heavily affected during the heat stress. The expression of SiSWEET13a was inhibited by heat stress in the stems, which may play a vital role in sugar transport between different tissues. These results provide new insights into the yield formation of crops under heat stress, which will provide guidance to crop breeding and cultivation.

The NAC gene family in the halophyte Limonium bicolor: Identification, expression analysis, and regulation of abiotic stress tolerance.

NAC transcription factors regulate plant growth, development, and stress responses. However, the number, types, and biological functions of Limonium bicolor LbNAC genes have remained elusive. L. bicolor secretes excessive salt ions through salt glands on its stems and leaves to reduce salt-induced damage. Here, we identified 63 NAC members (LbNAC1-63) in L. bicolor, which were unevenly distributed across eight chromosomes. Cis-elements in the LbNAC promoters were related to growth and development, stress responses, and phytohormone responses. We observed strong colinearity between LbNACs and GmNACs from soybean (Glycine max). Thus, LbNAC genes may share similar functions with GmNAC genes. Expression analysis indicated that 16 LbNAC genes are highly expressed in roots, stems, leaves, and flowers, whereas 17 LbNAC genes were highly expressed throughout salt gland development, suggesting that they may regulate this developmental stage. Silencing LbNAC54 in L. bicolor decreased salt gland density, salt secretion from leaves, and overall salt tolerance. In agreement, genes related to salt gland development were significantly downregulated in LbNAC54-silenced lines. Our findings shed light on LbNAC genes and help elucidate salt gland development and salt secretion in L. bicolor. Our data also provide insight into NAC functions in halophytes.

Oxidative stress, DNA damage, and gene expression in earthworms (Eisenia fetida) exposure to ethiprole.

To evaluate the potential ecotoxicity of ethiprole and early warning to earthworms (Eisenia fetida), different concentrations (0 mg·kg-1, 416 mg·kg-1, 625 mg·kg-1, and 1000 mg·kg-1) of ethiprole were added to artificial soil. The key bioindicators were measured and screened at 3 days, 7 days, 14 days, 21 days, and 28 days. The results show that the activity of catalase (CAT) was inhibited for all treatments during the whole exposure period. Besides, the olive tail moment (OTM) value increased gradually as the concentration got higher, which exhibited a dose-time-dependent relationship. Superoxide dismutase (SOD) gene reached the maximum on the 7th day. Mitochondrial large ribosomal RNA (l-rRNA) subunit gene was always in a downregulated state as the concentration increased. Our results show that different concentrations of ethiprole induced certain oxidative stress, DNA damage, and genotoxicity in earthworms. The CAT activity, OTM, and SOD gene could be the most sensitive biomarkers to monitor the toxicity of ethiprole in the soil.

Association between quality of life and resilience in infertile patients: a systematic review.

This systematic review was carried out to describe QoL and resilience in infertile patients, as well as the relationship between them, and to give a theoretical foundation for clinical practice. The databases of CNKI, Wanfang data, VIP database, PubMed, Web of Science, and Embase were searched without a time limit. A narrative synthesis of relevant articles was undertaken. This systematic review was registered on PROSPERO in advance. Of 21 studies eligible for inclusion in this review, 13 focused on the relationship between QoL and resilience, 5 on QoL influencing factors (resilience included), and 3 on mediation effect analysis on mental health (resilience as a mediator). Resilience can significantly predict the QoL of infertile patients. It seems plausible that more resilient couples will be less vulnerable to the stress of infertility. A global consortium of infertile population research could make cross-cultural comparisons of QoL and resilience possible. Future research should focus on resilience therapies. Systematic review registration: This systematic review was registered on PROSPERO in advance (CRD42023414706).

Marginal zone lymphoma with severe rashes: A case report.

BACKGROUND: Marginal zone lymphoma (MZL) is an indolent subtype of non-Hodgkin lymphoma (NHL), which is rare clinically with severe rashes as the initial symptom. CASE SUMMARY: This study reports a case of MZL with generalized skin rashes accompanied by pruritus and purulent discharge. First-line treatment with rituximab combined with zanubrutinib had poor effects. However, after switching to obinutuzumab combined with zanubrutinib, the case was alleviated, and the rashes disappeared. CONCLUSION: For patients with advanced stage MZL not benefiting from type I anti-CD20 monoclonal antibody (mAb) combination therapy, switching to a type II anti-CD20 mAb combination regimen may be considered. This approach may provide a new perspective in the treatment of MZL.

Protein tyrosine phosphatase 1B contributes to neuropathic pain by aggravating NF-κB and glial cells activation-mediated neuroinflammation via promoting endoplasmic reticulum stress.

BACKGROUND: Neuropathic pain is a prevalent and highly debilitating condition that impacts millions of individuals globally. Neuroinflammation is considered a key factor in the development of neuropathic pain. Accumulating evidence suggests that protein tyrosine phosphatase 1B (PTP1B) plays a crucial role in regulating neuroinflammation. Nevertheless, the specific involvement of PTP1B in neuropathic pain remains largely unknown. This study aims to examine the impact of PTP1B on neuropathic pain and unravel the underlying molecular mechanisms implicated. METHODS: In the current study, we evaluated the paw withdrawal threshold (PWT) of male rats following spared nerve injury (SNI) to assess the presence of neuropathic pain. To elucidate the underlying mechanisms, western blotting, immunofluorescence, and electron microscopy techniques were employed. RESULTS: Our results showed that SNI significantly elevated PTP1B levels, which was accompanied by an increase in the expression of endoplasmic reticulum (ER) stress markers (BIP, p-PERK, p-IRE1α, and ATF6) and phosphorylated NF-κB in the spinal dorsal horn. SNI-induced mechanical allodynia was impaired by the treatment of intrathecal injection of PTP1B siRNA or PTP1B-IN-1, a specific inhibitor of PTP1B. Moreover, the intrathecal administration of PTP1B-IN-1 effectively suppressed the expression of ER stress markers (BIP, p-PERK/p-eIF2α, p-IRE1α, and ATF6), leading to the inhibition of NF-κB, microglia, and astrocytes activation, as well as a decrease in pro-inflammatory cytokines, including TNF-α, IL-6, and IL-1ß. However, these effects were reversed by intrathecal administration of tunicamycin (Tm, an inducer of ER stress). Additionally, intrathecal administration of Tm in healthy rats resulted in the development of mechanical allodynia and the activation of NF-κB-mediated neuroinflammatory signaling. CONCLUSIONS: The upregulation of PTP1B induced by SNI facilitates the activation of NF-κB and glial cells via ER stress in the spinal dorsal horn. This, in turn, leads to an increase in the production of pro-inflammatory cytokines, thereby contributing to the development and maintenance of neuropathic pain. Therefore, targeting PTP1B could be a promising therapeutic strategy for the treatment of neuropathic pain.

Association between dietary intake of saturated fatty acid subgroups and breast cancer risk.

The impact of dietary saturated fatty acids (SFAs) on breast cancer risk may vary depending on their carbon chain lengths, attributable to the discrepancy in their dietary sources and biological activities. The associations between SFA subgroups classified by chain length and breast cancer risk remain controversial. In this case-control study, we aimed to investigate the association between the dietary intake of SFA subgroups, classified by chain lengths, and odds of breast cancer in China. This study included 1661 cases of breast cancer (confirmed as primary and histologically) and 1674 frequency-matched controls. Face-to-face interviews were used to collect basic information, while dietary intake information was obtained by a food frequency questionnaire. The unconditional logistic regression model was used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs). All SFA subgroups were inversely associated with odds of breast cancer. The adjusted ORs (95% CIs) were 0.78 (0.61-0.99) for medium-chain SFAs, 0.50 (0.31-0.83) for long even-chain SFAs, 0.69 (0.54-0.88) for long odd-chain, and 0.67 (0.48-0.95) for very long-chain SFAs, respectively. In the restricted cubic spline (RCS) models, a non-linear M-shaped association was observed between long odd-chain SFAs and odds of breast cancer (Pnon-linearity = 0.007). However, the associations of medium-chain SFAs, long even-chain SFAs, and very long-chain SFAs did not reach statistical significance (Pnon-linearity > 0.05). No significant interactions were observed between all these four subgroups of SFAs and menopausal status or BMI. Our findings emphasize the significance of elucidating the associations of dietary SFAs according to chain lengths, providing insights into the etiology as well as the potential benefits of SFA-rich food intake in reducing the risk of breast cancer. Further prospective cohort studies and intervention studies are warranted to confirm these findings and identify the underlying mechanisms of the association between dietary SFAs and breast cancer.

Acupuncture for postpartum diastasis recti abdominis and its effects on abdominal circumference, separation distance of rectus abdominis. / é’ˆåˆºæ²»ç–—äº§åŽè ¹ç›´è‚Œåˆ†ç¦»æ‚£è€ çš„ç–—æ•ˆåŠå¯¹è ¹å›´ã€è ¹ç›´è‚Œåˆ†ç¦»é—´è·çš„å½±å“.

OBJECTIVES: To observe the therapeutic efficacy of acupuncture and its effects on abdominal circumference, separation distance of rectus abdominis and quality of life in patients with postpartum diastasis recti abdominis on the basis of diastasis recti abdominis exercise. METHODS: A total of 87 postpartum women with diastasis recti abdominis were randomly divided into an observation group (44 cases) and a control group (43 cases) . The control group was treated with conventional diastasis recti abdominis rehabilitation exercise, including abdominal breathing training and supine leg lifting training, 3 times a day for 2 weeks. On the basis of the treatment in the control group, the observation group was treated with acupuncture at Zhongwan(CV 12), Qihai(CV 6)and bilateral Shenshu(BL 23), Daimai(GB 26), Daheng(SP 15), Zusanli (ST 36), etc., 30 min each time, once a day for 2 weeks. Before and after treatment, the separation distance of rectus abdominis, low back pain visual analogue scale (VAS) score, abdominal circumference and 36-item short form health survey questionnaire (SF-36) score in the two groups were compared, and the clinical effect was evaluated. RESULTS: After treatment, the separation distance of rectus abdominis, low back pain VAS scores, abdominal circumference of the two groups were lower than those before treatment(P<0.05), and the physiological function, physiological role, pain, mental health, emotional role, social function, energy, general health scores and total scores of SF-36 were higher than those before treatment(P<0.05); the separation distance of rectus abdominis, low back pain VAS score, abdominal circumference of the observation group were lower than those in the control group(P<0.05), the sub-item scores and total score of SF-36 of the observation group were higher than those in the control group(P<0.05).The effective rate of the observation group was 95.5% (42/44), which was higher than 79.1% (34/43) in the control group(P<0.05). CONCLUSIONS: Acupuncture combined with diastasis recti abdominis exercise can effectively relieve the low back pain of postpartum diastasis recti abdominis patients, promote the recovery of recti abdominis function, and improve the quality of life. The clinical effect is superior to diastasis recti abdominis exercise alone.

Clinical study of Edaravone Dexborneol combined with Tirofiban in treatment of Acute Cerebral Infarction.

Objective: To explore the clinical efficacy and safety of edaravone dexborneol combined with tirofiban in the treatment of acute cerebral infarction. Methods: This is a retrospective study. A total of 80 patients with acute cerebral infarction (ACI) treated in Cangzhou People's Hospital from March 2018 to December 2021 were selected, and randomly divided into the routine group(n=40) and intervention group(n=40) according to the principle of random draw. Neurological deficits in the two groups were evaluated and compared before and after treatment using the National Institutes of Health Stroke Scale (NIHSS). The quality of life of the patients was evaluated by the modified Rankin Scale (mRS). Results: Before treatment, NIHSS and mRS scores of the two groups were not statistically significant(p>0.05); the levels of Vmin and Qmin in the two groups showed no statistical significance(p>0.05); no statistical significance was found in CRP or IL-6 levels between the two groups(p>0.05). After treatment for 14 days, the NIHSS and mRS scores of the two groups both decreased, which was more significant in the intervention group(p<0.05); Vmin and Qmin levels increased in both groups, which was more obvious in the intervention group(p<0.05); CRP and IL-6 levels reduced in both groups, which was more remarkable in the intervention group(p<0.05). The incidences of relevant adverse drug reactions presented no differences between the two groups during treatment(p>0.05). Conclusion: Edaravone dexborneol combined with tirofiban in the treatment of ACI can effectively improve patients' neurological deficits, quality of life and cerebral blood flow, and reduce inflammatory factor levels, have significant clinical efficacy and high clinical treatment safety.

Three-dimensional analysis of hard and soft tissue changes in skeletal class II patients with high mandibular plane angle undergoing surgery.

This study aimed to study 3-dimensional (3D) changes of hard and soft tissues of skeletal class II patients after 2-jaw surgery and genioplasty. 32 adult patients diagnosed with mandibular hypoplasia who underwent 2-jaw surgery of maxillary impaction, mandibular advancement and genioplasty were enrolled. Cone-beam computed tomography and 3D stereophotogrammetry was conducted 1 week before and 6 months after surgery. Dolphin imaging software was used to establish a 3D digitizing model and 3D measurement system. Paired t-test was performed to compare the values before and after surgery. Pearson's correlation test assessed the degree of correlations between hard and soft tissue change. The mean impaction of the maxilla was 2.600 ± 3.088 mm at A. The mean advancement of the mandible was 7.806 ± 2.647 mm at B. There was a significant upward and forward movement for most landmarks of the nose and lip, while a significant decrease in nasal tip height (lateral view), upper lip height, and upper and lower vermilion height. The nose's width was significantly increased. For maxillary, Sn, Ac-r, Ac-l, and Ls demonstrated a significant correlation with A and U1 in the anteroposterior axis. However, there were no significant correlations among them in the vertical axis. For mandibular, Li demonstrated a significant correlation with L1 in the anteroposterior axis specifically for the mandible. Notably, correlations between the landmarks of the chin's hard and soft tissues were observed across all axes. The utilization of 3-D analysis facilitated a quantitative comprehension of both hard and soft tissues, thereby furnishing valuable insights for the strategic formulation of orthognathic treatment plans targeting patients with skeletal class II conditions.

Erythrocyte membrane n-3 PUFA are inversely associated with breast cancer risk among Chinese women.

The relationship between erythrocyte membrane n-3 PUFA and breast cancer risk is controversial. We aimed to examine the associations of erythrocyte membrane n-3 PUFA with odds of breast cancer among Chinese women by using a relatively large sample size. A case-control study was conducted including 853 newly diagnosed, histologically confirmed breast cancer cases and 892 frequency-matched controls (5-year interval). Erythrocyte membrane n-3 PUFA were measured by GC. Logistic regression and restricted cubic spline were used to quantify the association between erythrocyte membrane n-3 PUFA and odds of breast cancer. Erythrocyte membrane α-linolenic acid (ALA), docosapentaenoic acid (DPA) and total n-3 PUFA were inversely and non-linearly associated with odds of breast cancer. The OR values (95 % CI), comparing the highest with the lowest quartile (Q), were 0·57 (0·43, 0·76), 0·43 (0·32, 0·58) and 0·36 (0·27, 0·49) for ALA, DPA and total n-3 PUFA, respectively. Erythrocyte membrane EPA and DHA were linearly and inversely associated with odds of breast cancer ((EPA: ORQ4 v. Q1 (95 % CI) = 0·59 (0·45, 0·79); DHA: ORQ4 v. Q1 (95 % CI) = 0·50 (0·37, 0·67)). The inverse associations were observed between ALA and odds of breast cancer in postmenopausal women, and between DHA and oestrogen receptor+ breast cancer. This study showed that erythrocyte membrane total and individual n-3 PUFA were inversely associated with odds of breast cancer. Other factors, such as menopause and hormone receptor status, may warrant further investigation when examining the association between n-3 PUFA and odds of breast cancer.

Defect Synergistic Regulations of Li&Na Co-Doped Flexible Cu2 ZnSn(S,Se)4 Solar Cells Achieving over 10% Certified Efficiency.

Ion doping is an effective strategy for achieving high-performance flexible Cu2 ZnSn(S,Se)4 (CZTSSe) solar cells by defect regulations. Here, a Li&Na co-doped strategy is applied to synergistically regulate defects in CZTSSe bulks. The quality absorbers with the uniformly distributed Li and Na elements are obtained using the solution method, where the acetates (LiAc and NaAc) are as additives. The concentration of the harmful CuZn anti-site defects is decreased by 8.13% after Li incorporation, and that of the benign NaZn defects is increased by 36.91% after Na incorporation. Synergistic Li&Na co-doping enhances the carrier concentration and reduces the interfacial defects concentration by one order of magnitude. As a result, the flexible CZTSSe solar cell achieves a power conversion efficiency (PCE) of 10.53% with certified 10.12%. Because of the high PCE and the homogeneous property, the Li&Na co-doped device is fabricated to a large area (2.38 cm2 ) and obtains 9.41% PCE. The co-doping investigation to synergistically regulate defects provides a new perspective for efficient flexible CZTSSe solar cells.

Predictive value of CRP combined with peripheral blood cell ratio for the prognosis of advanced NSCLC.

Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for the vast majority. In recent years, the interaction between inflammation and tumorigenesis has become the focus of attention, which has also confirmed the importance of inflammatory markers such as C-reactive protein (CRP) in prognosis. In this study, we explored the effects of CRP, systemic inflammatory immune index (SII), and monocyte/lymphocyte ratio (MLR) on the prognosis of patients with advanced NSCLC. We conducted a retrospective study of 274 patients suffering from stage III/IV NSCLC. Among them, 224 patients served as the training set and 50 patients served as the validation set. The independent factors affecting PFS (Progression-Free Survival) and OS (Overall Survival) in the patients were analyzed by Cox regression. Our results showed that CPR (HR=1.691, P=0.004), SlI (HR=1.960, P<0.001), MLR (HR=1.578, P=0.003), CEA (HR=1.845, P=0.006), NSE (HR=2.138, P=0.003) and adrenal metastasis (HR=2.896, P<0.003) were independent factors affecting the PFS of NSCLC patients. SII (HR=1.645, P=0.004), CEA (HR=2.021, P=0.002) and brain metastasis (HR=2.899, P<0.001) were independent factors affecting the OS of NLSCL patients. The DCA curve demonstrated that the prediction model provided better clinical net benefit in predicting patients' 6-month PFS and 12-month OS under different threshold probabilities. DeLong test showed no significant difference between AUCs of SII and risk score (P>0.05). Compared with CEA, SII and risk score had higher predictive value for patients' 6-month PFS and 12-month OS (P<0.05). In conclusion, the results of this study indicate that serum inflammatory factor SII can be used as an independent indicator to evaluate 6-month PFS and 12-month OS in patients with advanced NSCLC, and its predictive value is similar to that of the nomogram model.

MdAIL5 overexpression promotes apple adventitious shoot regeneration by regulating hormone signaling and activating the expression of shoot development-related genes.

Adventitious shoot (AS) regeneration is a significant factor in the genetic transformation of horticultural plants. It is also a noteworthy approach to their vegetative propagation. AS regeneration remains highly dependent on the genotype or maturity of explants. We here found that the AS regeneration abilities of apple leaves were positively correlated with MdAIL5 expression. MdAIL5 overexpression dramatically increased AS regeneration efficiency. Notably, MdAIL5 overexpression could restore the AS formation ability of explants to a certain extent, which was lost with an increase in maturity. Endogenous hormone detection revealed that MdAIL5 overexpression changed the contents of auxin, cytokinin (CK), and other hormones in apple leaves. Transcriptome analysis revealed that many genes related to auxin, CK, and brassinolide signaling pathways were significantly and differentially expressed between MdAIL5-overexpressing transgenic apple and wild-type apple plants. Yeast one-hybrid assays, the electrophoretic mobility shift assay, and the dual-luciferase reporter assay revealed that MdAIL5 directly binds to MdARF9 and MdHB14 promoters and positively affects their expression. We here established a model of MdAIL5 regulating AS formation, which acts as a theoretical basis for facilitating genotype- or explant maturity-independent AS regeneration in the future.

Genome-wide identification of the mitogen-activated kinase gene family from Limonium bicolor and functional characterization of LbMAPK2 under salt stress.

BACKGROUND: Mitogen-activated protein kinases (MAPKs) are ubiquitous signal transduction components in eukaryotes. In plants, MAPKs play an essential role in growth and development, phytohormone regulation, and abiotic stress responses. The typical recretohalophyte Limonium bicolor (Bunge) Kuntze has multicellular salt glands on its stems and leaves; these glands secrete excess salt ions from its cells to mitigate salt damage. The number, type, and biological function of L. bicolor MAPK genes are unknown. RESULTS: We identified 20 candidate L. bicolor MAPK genes, which can be divided into four groups. Of these 20 genes, 17 were anchored to 7 chromosomes, while LbMAPK18, LbMAPK19, and LbMAPK20 mapped to distinct scaffolds. Structure analysis showed that the predicted protein LbMAPK19 contains the special structural motif TNY in its activation loop, whereas the other LbMAPK members harbor the conserved TEY or TDY motif. The promoters of most LbMAPK genes carry cis-acting elements related to growth and development, phytohormones, and abiotic stress. LbMAPK1, LbMAPK2, LbMAPK16, and LbMAPK20 are highly expressed in the early stages of salt gland development, whereas LbMAPK4, LbMAPK5, LbMAPK6, LbMAPK7, LbMAPK11, LbMAPK14, and LbMAPK15 are highly expressed during the late stages. These 20 LbMAPK genes all responded to salt, drought and ABA stress. We explored the function of LbMAPK2 via virus-induced gene silencing: knocking down LbMAPK2 transcript levels in L. bicolor resulted in fewer salt glands, lower salt secretion ability from leaves, and decreased salt tolerance. The expression of several genes [LbTTG1 (TRANSPARENT TESTA OF GL1), LbCPC (CAPRICE), and LbGL2 (GLABRA2)] related to salt gland development was significantly upregulated in LbMAPK2 knockdown lines, while the expression of LbEGL3 (ENHANCER OF GL3) was significantly downregulated. CONCLUSION: These findings increase our understanding of the LbMAPK gene family and will be useful for in-depth studies of the molecular mechanisms behind salt gland development and salt secretion in L. bicolor. In addition, our analysis lays the foundation for exploring the biological functions of MAPKs in an extreme halophyte.

NTRK1-mediated protection against manganese-induced neurotoxicity and cell apoptosis via IGF2 in SH-SY5Y cells.

BACKGROUND: Excessive manganese (Mn) exposure has been linked to neurotoxicity, cognitive impairments. Neurotrophic Receptor Kinase 1 (NTRK1) encodes Tropomyosin kinase A (TrkA), a neurotrophic receptor, as a mediator of neuron differentiation and survival. Insulin-like growth factor 2 (IGF2), a pivotal member of the insulin gene family, plays a crucial role in brain development and neuroprotection. Despite this knowledge, the precise mechanisms through which NTRK1 and IGF2 influence cell responses to Mn-induced neuronal damage remain elusive. METHODS: Cell apoptosis was assessed using CCK8, TUNEL staining, and Western blot analysis of cleaved Caspase-3. Lentiviral vectors facilitated NTRK1 overexpression, while small interfering RNAs (siRNAs) facilitated IGF2 knockdown. Real-time Quantitative PCR (qPCR) determined gene expression levels, while Western blotting measured protein expression. RESULTS: The study reveals that NTRK1 inhibits MnCl2-induced apoptosis in SH-SY5Y cells. NTRK1 overexpression significantly upregulated IGF2 expression, and subsequent siRNA-IGF2 experiments confirmed IGF2's pivotal role in NTRK1-mediated neuroprotection. Notably, the study identifies that NTRK1 regulates the expression of IGF2 in the neuroprotective mechanism with the involvement of ER stress pathways. DISCUSSION: The study reveals NTRK1's neuroprotective role via IGF2 against Mn-induced neurotoxicity and ER stress modulation in SH-SY5Y cells. These findings offer insights into potential therapies for neurodegenerative disorders related to Mn exposure and NTRK1 dysfunction, driving future research in this domain.