Spatial regulation of NMN supplementation on brain lipid metabolism upon subacute and sub-chronic PM exposure in C57BL/6 mice.

BACKGROUND: Atmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed. RESULTS: In this study, we examine the effect of ß-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis. CONCLUSIONS: This study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.

Unveiling the role of RARs in stomach adenocarcinoma: clinical implications and prognostic biomarkers.

Background: Retinoic acid receptors (RARs) family are known to play a significant role in the occurrence and development of tumors. However, the relationship between RARs and stomach adenocarcinoma (STAD) has not yet been clearly identified. The aim of this study is to evaluate the expression profile and clinical value of the RARs family in STAD. Methods: The expression level, clinical characteristics, prognostic value, immunity-related evaluations, genetic alteration and methylation site of RARs in STAD were explored using a series of online databases including gene expression profiling interactive analysis (GEPIA), tumor immune estimation resource (TIMER), University of Alabama at Birmingham cancer data (UALCAN), Human Protein Atlas (HPA), Kaplan-Meier plotter, gene set cancer analysis (GSCA), cBioPortal, MethSurv, GeneMANIA, LinkedOmics, Metascape, Search tool for the retrieval of interacting genes (STRING), tumor immune single-cell hub (TISCH) and cancer cell line encyclopedia (CCLE). Results: We discovered dramatically increased expression of RARA and decreased expression of RARB in STAD tissues, and many clinical variables were closely related to RARs. Notably, higher expressions of RARA and RARB as well as lower expression of RARG correlated with worse overall survival (OS) for STAD patients. The clinical value of prognostic model indicated that RARs were identified to be potential prognostic biomarkers for STAD patients. Moreover, RARB was closely related to immune cell infiltration, which had effect on the role of RARB in STAD prognosis. And the genetic alteration of RARB was significantly associated with the longer disease-free survival (DFS) of STAD patients. Additionally, some CpG sites of the RARs family were related with the prognosis of STAD patients. Functional enrichment analyses indicated that several pathways in STAD might be pivotal pathways regulated by RARs. At the single-cell level, there was some extent of infiltration of tumor microenvironment-related cells in the RARs expression in STAD. Conclusions: Our results evaluated the expression profile and clinical values of RARs in patients with STAD, which provided a basis for future in-depth exploration of the specific mechanisms of each member of RARs in STAD.

Phosphine-catalyzed enantioselective and diastereodivergent [3+2] cyclization for the construction of oxetane dispirooxindole skeletons.

We have developed a phosphine catalyzed asymmetric [3+2] cyclization of 3-oxetanone derived MBH carbonates with activated methyleneoxindole, to construct oxetane dispirooxindole skeletons. Diastereodivergent synthesis was realized via the control of the phosphine catalyst. The (-)-DIOP provides the syn diastereoisomers, while the spiro phosphine (R)-SITCP achieves the anti-epimers.

Plant growth and nitrate absorption and assimilation of two sweet potato cultivars with different N tolerances in response to nitrate supply.

In sweet potato, rational nitrogen (N) assimilation and distribution are conducive to inhibiting vine overgrowth. Nitrate (NO3-) is the main N form absorbed by roots, and cultivar is an important factor affecting N utilization. Herein, a hydroponic experiment was conducted that included four NO3- concentrations of 0 (N0), 4 (N1), 8 (N2) and 16 (N3) mmol L-1 with two cultivars of Jishu26 (J26, N-sensitive) and Xushu32 (X32, N-tolerant). For J26, with increasing NO3- concentrations, the root length and root surface area significantly decreased. However, no significant differences were observed in these parameters for X32. Higher NO3- concentrations upregulated the expression levels of the genes that encode nitrate reductase (NR2), nitrite reductase (NiR2) and nitrate transporter (NRT1.1) in roots for both cultivars. The trends in the activities of NR and NiR were subject to regulation of NR2 and NiR2 transcription, respectively. For both cultivars, N2 increased the N accumulated in leaves, growth points and roots. For J26, N3 further increased the N accumulation in these organs. Under higher NO3- nutrition, compared with X32, J26 exhibited higher expression levels of the NiR2, NR2 and NRT1.1 genes, a higher influx NO3- rate in roots, and higher activities of NR and NiR in leaves and roots. Conclusively, the regulated effects of NO3- supplies on root growth and NO3- utilization were more significant for J26. Under high NO3- conditions, J26 exhibited higher capacities of NO3- absorption and distributed more N in leaves and in growth points, which may contribute to higher growth potential in shoots and more easily cause vine overgrowth.

An Atomistic Level Investigation of the PFDTES-Graphene Interfacial Shear Strength and the Stick-Slip Mechanism.

1H,1H,2H,2H-Perfluorodecyltriethoxysilane (PFDTES) is the most widely used coating material with low surface energy and has the potential to be used as a dust-mitigating coating material during lunar landing missions. Graphene can be added to the PFDTES matrix to improve its mechanical properties. In this study, molecular dynamics simulations were performed to investigate the interfacial shear strength and friction mechanism between the PFDTES matrix and graphene. A systematic molecular dynamics (MD) simulation has been performed to calculate the interfacial shear strength of the PFDTES-graphene interface with considering the effect of graphene sliding velocity and vacancy defect density. For a pristine graphene layer with a size of 10 nm × 10 nm, the interfacial force between graphene and the PFDTES matrix is around 3 nN. Like other polymeric materials, the interfacial shear force exhibited stick-slip behavior under loading. The interfacial shear force will start to increase after the graphene starts sliding against the PFDTES matrix and reaches a stable plateau in a very short distance. It has been found that the influence of the interfacial shear strength from the sliding velocity of graphene is minimal. However, a significant increase in the interfacial shear strength has been observed after the graphene defect density increased; i.e., the magnitude of the shear force increased from 3 nN to around 14 nN after the defect density increased from 0% for pristine graphene to 40%. It has been found that vacancy defects will increase the fluctuation in the interfacial shear force, and it is due to not only the increased roughness near defects but also the stretched bonds in graphene under loading according to the distribution of the bond length. This study concluded that interfacial stick-slip behavior also exists in the PFDTES-graphene interface, and vacancy defects will have a significant improvement in the interfacial shear strength.

Rapid Construction of Cycloheptatriene through Organocatalyzed [4 + 3] Annulation of Coumalates.

A protocol for the construction of cycloheptatrienes has been developed. 4-(Dimethylamino)pyridine (DMAP) was found to be an efficient catalyst to promote the [4 + 3] annulation between coumalates and γ-alkyl-substituted allenoate or γ-aryl-3-butynoates to deliver a variety of cycloheptatrienes in moderate to good yield with excellent chemoselectivity. The asymmetric version of this annulation was also realized by using bifunctional phosphine catalyst to provide the chiral products with 32-97% ee and 29-64% yield.

Deapi-platycodin D3 attenuates osteoarthritis development via suppression of PTP1B.

Dysregulated chondrocyte metabolism is an essential risk factor for osteoarthritis (OA) progression. Maintaining cartilage homeostasis represents a promising therapeutic strategy for the treatment of OA. However, no effective disease-modifying therapy is currently available to OA patients. To discover potential novel drugs for OA, we screened a small-molecule natural product drug library and identified deapi-platycodin D3 (D-PDD3), which was subsequently tested for its effect on extracellular matrix (ECM) properties and on OA progression. We found that D-PDD3 promoted the generation of ECM components in cultured chondrocytes and cartilage explants and that intra-articular injection of D-PDD3 delayed disease progression in a trauma-induced mouse model of OA. To uncover the underlying molecular mechanisms supporting these observed functions of D-PDD3, we explored the targets of D-PDD3 via a screening approach integrating surface plasmon resonance (SPR) with liquid chromatography -tandem mass spectrometry (LC-MS/MS). The screening results suggested that D-PDD3 targeted tyrosine-protein phosphatase non-receptor type 1 (PTP1B), deletion of which restored chondrocyte homeostasis and markedly attenuated destabilization of the medial meniscus (DMM)-induced OA. Further cellular and molecular analyses showed that D-PDD3 maintained cartilage homeostasis by directly binding to PTP1B and consequently suppressing the PKM2/AMPK pathway. These findings demonstrated that D-PDD3 was a potential therapeutic drug for the treatment of OA and that PTP1B served as a protein target for the development of drugs to treat OA. This study provided significant insights into the development of therapeutics for OA treatment, which in turn helpd to improve the quality of life of OA patients and to reduce the health and economic burden.

OA is a degenerative disease with a high prevalence and consequently causes a burden to society. However, there is no convincing DMOAD exhibiting effective therapeutic effects on OA. In this study, we screened a small-molecule natural product drug library and identified deapi-platycodin D3, which was subsequently tested for its effect on extracellular matrix properties and on OA progression. Further cellular and in vivo experiments showed that D-PDD3 maintains cartilage homeostasis by directly binding to PTP1B and consequently suppressing the PKM2/AMPK pathway. Our results provided fundamental evidence for applying D-PDD3-based therapies against OA, which in turn helps to improve the quality of life in OA patients and to reduce the health and economic burdern.

A chlorin e6 derivative-mediated photodynamic therapy for mild to moderate acne: A prospective, single-blind, randomized, split-face controlled study.

BACKGROUND: Acne vulgaris is a chronic inflammatory skin disease involving the pilosebaceous unit. OBJECTIVE: To assess the efficacy and safety of a chlorin e6 derivative-mediated photodynamic therapy (STBF-PDT) in the treatment of mild to moderate acne patients. METHODS: In this prospective patient single-blind randomized split-face controlled study, patients diagnosed with mild to moderate acne were treated with four sessions of STBF-PDT on one-half of the face, while the other half were treated with the same dose of red-light treatment without photosensitizer. Follow-up assessment including the skin lesion clearance rate, facial fluorescence scattering spots on VISIA Porphyrins mode, and skin physiological parameters was conducted before and after treatment as well as 2 and 4 weeks after the final treatment. RESULTS: A total of 26 patients were recruited, of which 22 patients completed this study. STBF-PDT is significantly effective in improving lesions in patients with acne. The clearance rate of total lesions was 67.42±8.51 % in the STBF-PDT group and 41.05±11.97 % in the control group 4 weeks after the treatment (P < 0.001). The average clearance rate of inflammatory lesions was 84.41±7.13 % in the STBF-PDT group and 50.10±13.91 % in the control group, with a statistically significance (P < 0.0001). The skin sebum of the STBF-PDT side was significantly lower than that on the control side. There was no obvious adverse reaction especially no pain or reactive acne. CONCLUSION: STBF-PDT may be a safe and effective treatment for mild to moderate acne and can significantly inhibit sebum secretion.

CRY1 is involved in the take-off behaviour of migratory Cnaphalocrocis medinalis individuals.

BACKGROUND: Numerous insect species undertake long-distance migrations on an enormous scale, with great implications for ecosystems. Given that take-off is the point where it all starts, whether and how the external light and internal circadian rhythm are involved in regulating the take-off behaviour remains largely unknown. Herein, we explore this issue in a migratory pest, Cnaphalocrocis medinalis, via behavioural observations and RNAi experiments. RESULTS: The results showed that C. medinalis moths took off under conditions where the light intensity gradually weakened to 0.1 lx during the afternoon or evening, and the take-off proportions under full spectrum or blue light were significantly higher than that under red and green light. The ultraviolet-A/blue light-sensitive type 1 cryptochrome gene (Cmedcry1) was significantly higher in take-off moths than that of non-take-off moths. In contrast, the expression of the light-insensitive CRY2 (Cmedcry2) and circadian genes (Cmedtim and Cmedper) showed no significant differences. After silencing Cmedcry1, the take-off proportion significantly decreased. Thus, Cmedcry1 is involved in the decrease in light intensity induced take-off behaviour in C. medinalis. CONCLUSIONS: This study can help further explain the molecular mechanisms behind insect migration, especially light perception and signal transmission during take-off phases.

A comprehensive analysis of TRP-related gene signature, and immune infiltration in patients with colorectal cancer.

BACKGROUND: Transient receptor potential (TRP) channels are involved in the development and progression of tumors. However, their role in colorectal cancer (CRC) remains unclear, and this study aims to investigate the role of TRP-related genes in CRC. METHODS: Data was obtained from The Cancer Genome Atlas (TCGA) database, and analyses were conducted on the GSE14333 and GSE38832 datasets to assess the prognosis and mark TRP-related genes (TRGs). Subsequently, clustering analysis and immune infiltration analysis were performed to explore the relevant TRGs. In vitro validation of key TRGs' gene and protein expression was conducted using human colon cancer cells. RESULTS: Compared to normal tissues, 8 TRGs were significantly upregulated in CRC, while 11 were downregulated. TRPA1 was identified as a protective prognostic factor, whereas TRPM5 (HR = 1.349), TRPV4 (HR = 1.289), and TRPV3 (HR = 1.442) were identified as prognostic risk factors. Receiver operating characteristic (ROC) curves and Kaplan-Meier (KM) analyses yielded similar results. Additionally, lower expression of TRPA1 and higher expression of TRPV4 and TRPM5 were negatively correlated with patient prognosis, and experimental validation confirmed the underexpression of TRPA1 and overexpression of TRPV4 and TRPM5 in CRC cell lines. CONCLUSION: This study identifies a TRP channel-related prognosis in CRC, providing a novel approach to stratifying CRC prognosis.

Rapid Fabrication of Antilunar Dust Aluminum Surface by Nanosecond Laser Etching.

Although a dust-repellent surface is desirable for lunar exploration missions, its fabrication process is complicated and time-consuming. Herein, we report a simple and fast method to fabricate a lunar dust-repellent surface by texturing on an Al substrate via nanosecond laser etching. The laser-induced photothermal effect can rapidly create hierarchical papillary structures on 25 × 25 mm Al substrates (within 30 s). Both atomic force microscopy (AFM) and in situ scanning electron microscopy (SEM) reveal that such structures enable a reduced contact area between the Al substrate and lunar dust and thus reduced adhesion. The reduced dust adhesion force of Al substrates facilitates improving their antidust performance. By optimizing processing parameters, the Al substrate etched with a laser scanning spacing of 80 µm exhibits a lower dust adhesion force (9.58 nN) due to the smallest contact area with dust. Accordingly, its static antilunar dust performance (dust coverage of 1.95%) is significantly improved compared to the pristine Al substrate (dust coverage of 12.98%). Besides, the accumulated dust on the laser-etched Al substrates with low surface adhesion force is easily cleaned up by flipping and gravity (the dust residual rates are less than 17%). The Al substrate with excellent antidust ability presents good potential for lunar exploration missions.

Establishment of iPS cell line (SDQLCHi080-A) from a patient with GM1 gangliosidosis due to GLB1 mutation.

GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder caused by defects in the beta-galactosidase (GLB1) gene, which results in accumulation of GM1 gangliosides and related glycoconjugates in the lysosomes leading to lysosomal swelling, cellular damage, and organ dysfunction. We generated SDQLCHi080-A cell line from a patient with GM1 gangliosidosis carrying mutations of c.523C > T and c.574T > C > T in the GLB1 gene. The cell line exhibited typical iPSC morphology, expressed high levels of stemness markers, exhibited normal karyotype, and has the capability to differentiate into three germ layers. This cell line could provide a useful GM1 gangliosidosis model in vitro for further study.

The effects of baicalin in depression: preclinical evidence construction based on meta-analysis.

Background: Depression manifests as a mental disorder characterized by a low mood, suicidal tendencies, disturbances in sleep-wake cycles, psychomotor agitation, and pronounced feelings of hopelessness and anhedonia. Baicalin, a natural flavonoid compound, shows significant promise in alleviating depressive symptoms in animals. This study aims to assess the impact of baicalin on experimental models of depression. Methods: A systematic search of electronic databases was conducted using the search terms "baicalin" AND "depression" OR "depressed" OR "anti-depression". Preclinical animal models representing experimental depression were included in the analysis. The risk of bias in the included studies was evaluated using the CAMARADES tools. Results: Baicalin significantly increased sucrose preference test (SPT) [SMD= 21.31, 95%CI (16.32, 26.31), P < 0.00001]. mThe tail suspension test (TST) duration significantly decreased in the baicalin group compared to the model group [SMD = -39.3, 95%CI (-49.71, -28.89), P < 0.0001]. Furthermore, baicalin reduced immobility time in rats subjected to the forced swim test (FST) [SMD = -39.73, 95%CI (-48.77, -30.69) P < 0.0001]. Compared to the model group, baicalin treatment also significantly increased the frequency of crossings in the open field test (OFT) [SMD = 32.44, 95%CI (17.74, 47.13), P < 0.00001]. Conclusion: Baicalin significantly improves the manifestations of depressive symptoms. The effect of baicalin against depression is exerted through its anti-inflammatory actions, inhibition of oxidative stress, regulation of the HPA axis, and restoration of neuroplasticity. Future studies will be needed to further explore how these promising preclinical findings can be translated into clinical treatment for depression. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023472181.

HPV specificity and multiple infections and association with cervical cytology in Chongqing, China: a cross-sectional study.

BACKGROUND: It is important to assess the relationship between specific HPV genotype or multiple infection and cervical cytology. The protection provided by the HPV vaccine is type-specific, and the epidemiology feature of coinfections needs to be investigated. The aim is to provide baseline information for developing HPV vaccination and management of HPV-positive populations in the region. METHODS: A total of 3649 HPV-positive women were collected from 25,572 women who underwent 15 HR-HPV genotypes and ThinPrep cytologic test (TCT) results. Logistic regression was used to determine the correlation between the risk of cytology abnormalities and specific HPV infection. We calculated odds ratios (ORs) to assess coinfection patterns for the common two-type HPV infections. chi-squared test was used to estimate the relationship between single or multiple HPV (divided into species groups) infection and cytology results. RESULTS: The results showed there was a positive correlation between HPV16 (OR = 4.742; 95% CI 3.063-7.342) and HPV33 (OR = 4.361; 95% CI 2.307-8.243) infection and HSIL positive. There was a positive correlation between HPV66 (OR = 2.445; 95% CI 1.579-3.787), HPV51 (OR = 1.651; 95% CI 1.086-2.510) and HPV58(OR = 1.661; 95% CI 1.166-2.366) infection and LSIL. Multiple HPV infections with α9 species (OR = 1.995; 95% CI 1.101-3.616) were associated with a higher risk of high-grade intraepithelial lesions (HSIL) compared with single HPV infection. There were positive correlations between HPV66 and HPV56 (α6) (OR = 3.321; 95% CI 2.329-4.735) and HPV39 and HPV68 (α7). (OR = 1.677; 95% CI 1.127-2.495). There were negative correlations between HPV52, 58, 16 and the other HPV gene subtypes. CONCLUSION: HPV33 may be equally managed with HPV16. The management of multiple infections with α9 may be strengthened. The 9-valent vaccine may provide better protection for the population in Chongqing currently. The development of future vaccines against HPV51 and HPV66 may be considered in this region.

Exploring the relationship between anal fistula and colorectal cancer based on Mendelian randomization and bioinformatics.

The association between anal fistula patients and colorectal cancer, as well as the potential pathophysiological mechanisms, remains unclear. To explore the relationship between anal fistula and colorectal cancer and its potential mechanisms. Analysis of GEO and TCGA databases. Disease-related genes were also referenced from Coremine Medical, GeneCard and OMIM. Core hub genes were identified through protein-protein interaction analysis by intersecting differentially expressed genes from the datasets with disease data. On one hand, a prognostic model was developed using genes and its prognostic role was validated. On the other hand, the optimal diagnostic genes were selected through machine learning. Mendelian randomization (MR) analysis was conducted to explore the potential causal link between anal fistula and colorectal cancer. Thirteen core genes were identified (TMEM121B, PDGFRA, MID2, WNT10B, HOXD13, BARX1, SIX2, MMP1, SNAL1, CDKN2A, ITGB3, TIMP1, CALB2). Functional enrichment analysis revealed that the intersecting genes between anal fistula and colorectal cancer were associated with extracellular matrix components, signalling pathways, cell growth, protein modification, as well as important roles in cellular activities, tissue and organ development, and biological function maintenance. These genes were also involved in pathways related to Wnt signalling and colorectal cancer development. Prognostic analysis and immune infiltration analysis indicated a close relationship between core hub genes and the prognosis and immune infiltration in colorectal cancer. Machine learning showed that core genes played an essential role in the diagnostic differentiation of colorectal cancer. MR results suggested no causal relationship between anal fistula and colorectal cancer. This study identified shared core genes between anal fistula and colorectal cancer, involved in various pathways related to tumour development. These genes play crucial roles in prognosis and diagnosis.

DefendFL: A Privacy-Preserving Federated Learning Scheme Against Poisoning Attacks.

Federated learning (FL) has become a popular mode of learning, allowing model training without the need to share data. Unfortunately, it remains vulnerable to privacy leakage and poisoning attacks, which compromise user data security and degrade model quality. Therefore, numerous privacy-preserving frameworks have been proposed, among which mask-based framework has certain advantages in terms of efficiency and functionality. However, it is more susceptible to poisoning attacks from malicious users, and current works lack practical means to detect such attacks within this framework. To overcome this challenge, we present DefendFL, an efficient, privacy-preserving, and poisoning-detectable mask-based FL scheme. We first leverage collinearity mask to protect users' gradient privacy. Then, cosine similarity is utilized to detect masked gradients to identify poisonous gradients. Meanwhile, a verification mechanism is designed to detect the mask, ensuring the mask's validity in aggregation and preventing poisoning attacks by intentionally changing the mask. Finally, we resist poisoning attacks by removing malicious gradients or lowering their weights in aggregation. Through security analysis and experimental evaluation, DefendFL can effectively detect and mitigate poisoning attacks while outperforming existing privacy-preserving detection works in efficiency.

Establishment of a human induced pluripotent stem cell line (SDQLCHi079-A) from a patient with Johanson-Blizzard syndrome carrying heterozygous mutation in UBR1 gene.

Johanson-Blizzard syndrome (JBS) is an autosomal recessive disorder. We established an induced pluripotent stem cell (iPSC) line from peripheral blood mononuclear cells of a 2-year-old boy with Johanson-Blizzard syndrome carrying a compound heterozygous mutation of c.3167C>G (p.S1056X) and c.1911 + 14C>G(splicing) in the UBR1 gene. This iPSC line was free of exogenous gene, expressed stemness markers, exhibited differentiation potential, had normal karyotype and harbored the same mutations found in the patient. The iPSC cellline can serve as a disease model in drug development and novel personalized therapies.

It is not a vacation of leisure: The effect of maternity-leave stigma on fertility intentions in China.

In response to the public's puzzle about why maternity leave has unexpectedly failed to improve fertility problem in the Chinese context of a widespread extension of maternity leave, our study concentrates on a prevailing stigmatization phenomenon of maternity leave in the workplace, proposes the construct "maternity-leave stigma", operationalizes it, and examines its probable detrimental effect on working individuals' fertility intentions drawing on conservation of resources theory, self-verification theory, and research on stigma and psychological contract violation. Conceptually, maternity-leave stigma is a kind of workplace stigma that primarily depicts the extent to which working individuals in the reproductive period view maternity leave or the event of taking maternity leave in a biased way. It mainly consists of four subdimensions called cognitive stigma, emotional stigma, moral stigma, and consequence stigma. Based on multiple analyses of the three-stage questionnaire survey data from working individuals of childbearing age in China, Study 1 (N1 = 296, N2 = 340) acquires a 12-item maternity-leave stigma scale with good reliability and validity and Study 2 (N2 = 340) substantiates that, working individuals' maternity-leave stigma tends to directly and indirectly inhibit their fertility intentions and their anticipatory psychological contract violation from organization is the crucial mediator. Moreover, working women are inclined to display a much stronger inhibiting effect of maternity-leave stigma on fertility intentions compared to working men. Our findings therefore resolve the public's puzzle, enrich workplace stigma, deepen the implementation effectiveness research of maternity leave policy, and are of practical implications for building a fertility-friendly society.

PDZK1 protects against mechanical overload-induced chondrocyte senescence and osteoarthritis by targeting mitochondrial function.

Mechanical overloading and aging are two essential factors for osteoarthritis (OA) development. Mitochondria have been identified as a mechano-transducer situated between extracellular mechanical signals and chondrocyte biology, but their roles and the associated mechanisms in mechanical stress-associated chondrocyte senescence and OA have not been elucidated. Herein, we found that PDZ domain containing 1 (PDZK1), one of the PDZ proteins, which belongs to the Na+/H+ Exchanger (NHE) regulatory factor family, is a key factor in biomechanically induced mitochondrial dysfunction and chondrocyte senescence during OA progression. PDZK1 is reduced by mechanical overload, and is diminished in the articular cartilage of OA patients, aged mice and OA mice. Pdzk1 knockout in chondrocytes exacerbates mechanical overload-induced cartilage degeneration, whereas intraarticular injection of adeno-associated virus-expressing PDZK1 had a therapeutic effect. Moreover, PDZK1 loss impaired chondrocyte mitochondrial function with accumulated damaged mitochondria, decreased mitochondrion DNA (mtDNA) content and increased reactive oxygen species (ROS) production. PDZK1 supplementation or mitoubiquinone (MitoQ) application alleviated chondrocyte senescence and cartilage degeneration and significantly protected chondrocyte mitochondrial functions. MRNA sequencing in articular cartilage from Pdzk1 knockout mice and controls showed that PDZK1 deficiency in chondrocytes interfered with mitochondrial function through inhibiting Hmgcs2 by increasing its ubiquitination. Our results suggested that PDZK1 deficiency plays a crucial role in mediating excessive mechanical load-induced chondrocyte senescence and is associated with mitochondrial dysfunction. PDZK1 overexpression or preservation of mitochondrial functions by MitoQ might present a new therapeutic approach for mechanical overload-induced OA.

Quantitative trait locus analysis of gray leaf spot resistance in the maize IBM Syn10 DH population.

KEY MESSAGE: The exploration and dissection of a set of QTLs and candidate genes for gray leaf spot disease resistance using two fully assembled parental genomes may help expedite maize resistance breeding. The fungal disease of maize known as gray leaf spot (GLS), caused by Cercospora zeae-maydis and Cercospora zeina, is a significant concern in China, Southern Africa, and the USA. Resistance to GLS is governed by multiple genes with an additive effect and is influenced by both genotype and environment. The most effective way to reduce the cost of production is to develop resistant hybrids. In this study, we utilized the IBM Syn 10 Doubled Haploid (IBM Syn10 DH) population to identify quantitative trait loci (QTLs) associated with resistance to gray leaf spot (GLS) in multiple locations. Analysis of seven distinct environments revealed a total of 58 QTLs, 49 of which formed 12 discrete clusters distributed across chromosomes 1, 2, 3, 4, 8 and 10. By comparing these findings with published research, we identified colocalized QTLs or GWAS loci within eleven clustering intervals. By integrating transcriptome data with genomic structural variations between parental individuals, we identified a total of 110 genes that exhibit both robust disparities in gene expression and structural alterations. Further analysis revealed 19 potential candidate genes encoding conserved resistance gene domains, including putative leucine-rich repeat receptors, NLP transcription factors, fucosyltransferases, and putative xyloglucan galactosyltransferases. Our results provide a valuable resource and linked loci for GLS marker resistance selection breeding in maize.