Wei-fu-chun tablet halted gastric intestinal metaplasia and dysplasia associated with inflammation by regulating the NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Chi006Eese herbal medicine Weifuchun Tablets (WFC) approved by the State Food and Drug Administration in 1982 has been widely used in treating a variety of chronic stomach disorders including Chronic atrophic gastritis (CAG) and Gastric precancerous lesions in China clinically. This study aimed to investigate the efficacy and potential mechanism of WFC in treating Gastric intestinal metaplasia (GIM) and Gastric dysplasia (GDys). MATERIALS AND METHODS: Rat GIM and GDys established by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) combined with hot paste, ethanol injury, and intermittent fasting were intervened by WFC. Body weight, histopathology, pH of gastric acid, pepsin activity, intestinal metaplasia index and inflammation were detected. Rat bone marrow derived macrophages (BMDMs) pretreated with WFC were stimulated by LPS. Inflammatory factors and the nuclear factor-kappa B (NF-κB) pathway were assessed. GES-1 cells pretreated by WFC were stimulated by MNNG and TNF-α, intestinal metaplasia index, the NF-κB pathway and interaction between P65 and CDX2 were detected. RESULTS: WFC improved rat body weight, histopathology, pH value of gastric acid, activity of gastric pepsin, intestinal metaplasia (CDX2), inflammation (IL-1ß, IL-6 and TNF-α), macrophage aggregation (CD68) in gastric mucosa in rat GIM and GDys. WFC inhibited inflammation (IL-1ß and TNF-α) by inactivating the NF-κB pathway. WFC reduced the expression of CDX2 by inhibiting the binding of CDX2 promoter TSS upstream region with p65. CONCLUSION: WFC blocked GIM and GDys associated with inflammation by regulating the NF-κB pathway.

The anti-hepatocellular carcinoma effect of Aidi injection was related to the synergistic action of cantharidin, formononetin, and isofraxidin through BIRC5, FEN1, and EGFR.

ETHNOPHARMACOLOGICAL RELEVANCE: Aidi injection (ADI) is a popular anti-tumor Chinese patent medicine, widely used in clinics for the treatment of hepatocellular carcinoma (HCC) with remarkable therapeutic effects through multiple targets and pathways. However, the scientific evidence of the synergistic role of the complex chemical component system and the potential mechanism for treating diseases are ignored and remain to be elucidated. AIM OF THE STUDY: This study aimed to elucidate and verify the cooperative association between the potential active ingredient of ADI, which is of significance to enlarge our understanding of its anti-HCC molecular mechanisms. MATERIALS AND METHODS: Firstly, the anti-HCC effect of ADI was evaluated in various HCC cells and the zebrafish xenograft model. Subsequently, a variety of bioinformatic technologies, including network pharmacology, weighted gene co-expression network analysis (WGCNA), meta-analysis of gene expression profiles, and pathway enrichment analysis were performed to construct the competitive endogenous RNA (ceRNA) network of ADI intervention in HCC and to establish the relationship between the critical targets/pathways and the key corresponding components, which were involved in ADI against HCC in a synergistic way and were validated by molecular biology experiments. RESULTS: ADI exerted remarkable anti-HCC in vitro cells and in vivo zebrafish model, especially that the Hep 3B2.1-7 cell showed substantial sensibility to ADI. The ceRNA network revealed that the EGFR/PI3K/AKT signaling pathway was identified as the promising pathway. Furthermore, the meta-analysis also demonstrated the critical role of BIRC5 and FEN1 as key targets. Finally, the synergistic effect of ADI was revealed by discovering the inhibitory effect of cantharidin on BIRC5, formononetin on FEN1 and EGFR, as well as isofraxidin on EGFR. CONCLUSION: Our study unveiled that the incredible protective effect of ADI on HCC resulted from the synergistic inhibition effect of cantharidin, formononetin, and isofraxidin on multiple targets/pathways, including BIRC5, FEN1, and EGFR/PI3K/AKT, respectively, providing a scientific interpretation of ADI against HCC and a typical example of pharmacodynamic evaluation of other proprietary Chinese patent medicine.

Assessing and optimizing the effectiveness of protected areas along China's coastal region: A social-ecological protected area network study.

Effectiveness of protected areas (EPA) evaluation has been used to measure the effectiveness of existing protected areas (PAs) and to identify prioritized and inefficient PAs. However, the current EPA evaluation remains incomplete, primarily due either to the scale of evaluation focusing on only isolated PAs without considering network connectivity or to the difficulty of balancing social and ecological synergy in practice. To address this issue, we proposed a social-ecological connectivity pathway to maximize the evaluation and optimization of EPA in a coastal region: first, we selected social and ecological indicators for habitat suitability evaluation and simulated the protected area network (PAN); second, we evaluated the rationality of network connectivity; and ultimately, we identified conservation gaps to the post-2020 global biodiversity target. Considering the complexity of coastal ecosystems, we selected the four coastal cities of the Shandong Peninsula, China as a case study. We find that (1) the social-ecological PAN consists of 370 primary corridors and 110 secondary corridors; there are 12 cross-ecosystem types in the identified PANs, three of which span marine to terrestrial ecosystems, while the remaining nine span terrestrial interior ecosystems; (2) 66 nodes were identified as spatial gaps; the benefit gap indicated that 51.75% of PAs were inefficiently protected but 48.25% were appropriately protected; regarding quantity gap, the marine PAs gap (25.41%) is much larger than the terrestrial PAs gap (15.80%), suggesting a possible priority in the marine PAs appropriately. Our study reveals that the EPA in the coastal region is currently weak and urgently needs to improve. Thus, we propose measures to optimize the EPA and suggest its potential application to other PAs in complex and vulnerable coastal regions.

Semisolid medium internal phase emulsions stabilized by dendritic-like mushroom cellulose nanofibrils: Concentration effect and stabilization mechanism.

Emulsions with reduced fat and natural stabilizers are currently prevalent. Herein, semisolid emulsions with an oil phase of 50 % were successfully prepared using cellulose nanofibrils from mushroom stipes as stabilizers. Cellulose nanofibrils obtained by high-pressure homogenization were dendritic-like and possessed a contact angle of 70.50 ± 0.41°. The rheological properties and stability of emulsions increased significantly as nanocellulose concentrations increased from 5 to 20 mg/mL, while nanocellulose at 25-30 mg/mL significantly reduced the storage stability and anti-lipid oxidation ability of emulsions. The microstructure of semisolid emulsions demonstrated that nanocellulose fibers at 20 mg/mL could stabilize emulsions by forming compact interfacial films around droplets and creating intensive bridging networks between neighboring droplets, while nanofibers at concentrations over 20 mg/mL easily clustered in the aqueous phase, making the droplets more susceptible to aggregation and demulsification. The results demonstrate that cellulose nanofibrils from mushroom byproducts have the potential to stabilize semisolid food-grade emulsions.

Coiled-coil scallops (Chlamys farreri) peptide hydrogel with metal ionic and temperature tunable assembly.

Self-assembly of peptides is a powerful method of preparing nanostructured materials. Peptides frequently utilize charged groups as a convenient switch for controlling assembly state by pH, ionic strength or temperature. In this study, the molecular properties and gel-forming ability of Chlamys farreri protein hydrolysates were studied. According to self-assembled theory, the presence of isoleucine at position 'a' and leucine at 'd' causes a switch between coiled-coil structures. Compared to P-2-CG, the components of α-helix (23.60 ± 0.56%) were changed into ß-sheet (4.83 ± 2.86%) in the secondary structure of the hydrogel induced by ZnCl2. NMR siginals appeared at high field,which indicated hydrogen bonds were formed between P-2-CG and solvent environments at 20 °C. With temperature going up, the hydrogen bonds were broken and nanofibrils were changed into dense aggregates. We expected that P-2-CG could provide a new candidate for preparing metal-induced nanofibers or hydrogels with further applications in food industry.

Synergistic effect of residual sugar on freeze-thaw stability of high internal phase emulsions using glycosylated cod protein as interface stabilizer.

Nowadays, glycosylated protein seems to be one of the most effective stabilizers for preparing freeze-thaw stabile emulsion; nevertheless, few papers mentioned the relationship between the residual free sugars after the glycosylation reaction and the freeze-thaw stability of high internal phase emulsions (HIPEs). Herein, glucose was used to prepare glycosylated cod proteins (GCPs). The synergistic effect was related to the grafting degree of GCP, and the amount of glucose added to prepare freeze-thaw stable HIPEs was reduced from 20% to 4% when the grafting degree of GCP increased from 0% to 31.58% (i.e. 12% GCP). This might be due to fewer ice crystals forming in water phase or less destruction of emulsion droplets by ice crystals. The obtained results in this study will allow developing freeze-thaw stable HIPEs or new frozen ingredients.

The predictive value of modified-DeepSurv in overall survivals of patients with lung cancer.

The traditional prognostic model may induce the possibility of incorrect assessment of mortality risk under the assumption of linearity. It is urgent to develop a non-linearity precise prognostic model for achieving personalized medicine in lung cancer. In our study, we develop and validate a prognostic model "Modified-DeepSurv" for patients with lung carcinoma based on deep learning and evaluate its value for prognosis, while Cox proportional hazard regression was used to develop another model "CPH." The C-index of the Modified-DeepSurv and CPH was 0.956 (95% confidence interval [CI]: 0.946-0.974) and 0.836 (95% CI: 0.774-0.896), respectively, in the training cohort, while the C-index of the Modified-DeepSurv and CPH was 0.932 (95%CI: 0.908-0.964) and 0.777 (95%CI: 0.633-0.919), respectively, in the test dataset. The Modified-DeepSurv model visualization was realized by a user-friendly graphic interface. Modified-DeepSurv can effectively predict the survival of lung cancer patients and is superior to the conventional CPH model.

Sacral terminal filar cyst: a distinct variant of spinal meningeal cyst and midterm clinical outcome following combination resection surgery.

Objective: Spinal meningeal cysts (SMCs) are currently classified into three types: extradural cysts without nerve root fibers (Type I), extradural cysts with nerve root fibers (Type II), and intradural cysts (Type III). However, the sacral terminal filar cyst is a distinct subtype with the filum terminale rather than nerve roots within the cyst. This study aimed to investigate the clinicoradiological characteristics and surgical outcomes of sacral terminal filar cysts. Methods: A total of 32 patients with sacral terminal filar cysts were enrolled. Clinical and radiological profiles were collected. All patients were surgically treated, and preoperative and follow-up neurological functions were evaluated. Results: Chronic lumbosacral pain and sphincter dysfunctions were the most common symptoms. On MRI, the filum terminale could be identified within the cyst in all cases, and low-lying conus medullaris was found in 23 (71.9%) cases. The filum terminale was dissociated and cut off in all cases, and the cyst wall was completely resected in 23 (71.9%) cases. After a median follow-up period of 26.5 ± 15.5 months, the pain and sphincter dysfunctions were significantly improved (both P < 0.0001). The cyst recurrence was noted in only 1 (3.1%) case. Conclusions: Sacral terminal filar cysts are rare, representing a distinct variant of SMCs. Typical MRI features, including filum terminale within the cyst and low-lying conus medullaris, may suggest the diagnosis. Although the optimal surgical strategy remains unclear, we recommend a combination of resection of the cyst wall and dissociation of the filum terminale. The clinical outcomes can be favorable.

Functionalized Cerium Dioxide Nanoparticles with Antioxidative Neuroprotection for Alzheimer's Disease.

Background: Oxidative stress induced reactive oxygen species (ROS) and aggregation of amyloid ß (Aß) in the nervous system are significant contributors to Alzheimer's disease (AD). Cerium dioxide and manganese oxide are known as to be effective and recyclable ROS scavengers with high efficiency in neuroprotection. Methods: A hollow-structured manganese-doped cerium dioxide nanoparticle (LMC) was synthesized for loading Resveratrol (LMC-RES). The LMC-RES were characterized by TEM, DLS, Zeta potential, and X-ray energy spectrum analysis. We also tested the biocompatibility of LMC-RES and the ability of LMC-RES to cross the blood-brain barrier (BBB). The antioxidant effects of LMC-RES were detected by SH-SY5Y cells. Small animal live imaging was used to detect the distribution of LMC-RES in the brain tissue of AD mice. The cognitive abilities of mice were tested by water maze and nesting experiments. The effects of LMC-RES in reducing oxidative stress and protecting neurons was also explored by histological analysis. Results: The results showed that LMC-RES had good sustained release effect and biocompatibility. The drug release rate of LMC-RES at 24 hours was 80.9 ± 2.25%. Meanwhile, LMC-RES could cross the BBB and enrich in neurons to exert antioxidant effects. In Aß-induced SH-SY5Y cells, LMC-RES could inhibits oxidative stress through the Nrf-2/HO-1 signaling pathway. In AD model mice, LMC-RES was able to reduce ROS levels, inhibit Aß-induced neurotoxicity, and protect neurons and significantly improve cognitive deficits of AD mice after drug administration. Conclusion: LMC-RES can effectively across the BBB, reduce oxidative stress, inhibit Aß aggregation, and promote the recovery of neurological function.

Exploring safety capacity from a risk and safety information integration perspective: Connotation, dimension mining and dimensionality reduction.

With the development of safety science, the concept of safety capacity (SC) has been proposed. SC has been applied in many fields. Concurrently, there has been an active and robust development of research pertaining to it. However, SC research mainly focuses on practical engineering problems, and SC research is only regarded as the establishment of a quantitative model for system safety. Hence, the theoretical study of SC is ignored. Indeed, the integrated theoretical system and connotation of SC are lacking. In this study, an attempt is made to enrich the theoretical connotation of SC. The following aspects of theoretical exploration are included: (a) The theoretical connotation of SC is redefined so that the lack of theory with respect to SC can be made up. Moreover, research directions of SC are indicated as dimension mining (DM) and dimensionality reduction (DR). (b) The application value of safety similarity theory in the DM of SC is expounded according to the principle of analogism. Core principles of DM are proposed and explained. (c) Common methods of DR are summarized, and the one-sided cognition of DR for the current SC research is corrected. A case study of an explosion accident caused by a boiler water shortage is employed for further discussion. For the investigation of the explosion accident using fault tree analysis (FTA), DR of SC is utilized to provide a more comprehensive explanation. Therefore, the proposed SC is proven to be practical for the analysis of system safety. The results obtained from this study have important implications for research and practice of SC.

Bacillus subtilis partially inhibits African swine fever virus infection in vivo and in vitro based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II.

IMPORTANCE: African swine fever virus (ASFV) is a highly fatal swine disease that severely affects the pig industry. Although ASFV has been prevalent for more than 100 years, effective vaccines or antiviral strategies are still lacking. In this study, we identified four Bacillus subtilis strains that inhibited ASFV proliferation in vitro. Pigs fed with liquid biologics or powders derived from four B. subtilis strains mixed with pellet feed showed reduced morbidity and mortality when challenged with ASFV. Further analysis showed that the antiviral activity of B. subtilis was based on its metabolites arctiin and genistein interfering with the function of viral topoisomerase II. Our findings offer a promising new strategy for the prevention and control of ASFV that may significantly alleviate the economic losses in the pig industry.

SUV39H1 is a novel biomarker targeting oxidative phosphorylation in hepatitis B virus-associated hepatocellular carcinoma.

BACKGROUND: As a histone methyltransferase, suppressor of variegation 3-9 homolog 1 (SUV39H1) plays an important role in the occurrence and development of cancer. To explore the mechanism and biological function of SUV39H1 in hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) can gain an insight into the pathogenesis of HBV-HCC. METHODS: The effect of HBV infection on SUV39H1 in hepatoma cells was detected. CCK-8, colony growth assay and wound healing assay were used to assess the proliferation and migration of HBV-positive hepatoma cells. RNA sequencing (RNA-seq) was applied to find differential genes and enriched pathways. The serum SUV39H1 level in HBV-HCC patients was detected and its correlation with clinical indicators was analyzed. RESULTS: SUV39H1 was increased by HBV infection and promoted the proliferation and migration of hepatoma cells. SUV39H1 could upregulate the expression of mitochondrial oxidative phosphorylation (OXPHOS) pathway-related genes. OXPHOS pathway inhibitors could reduce the capacity of proliferation and migration of hepatoma cells after overexpressing SUV39H1. Serum SUV39H1 levels were higher in chronic hepatitis B (CHB) patients than in healthy controls and higher in HBV-HCC patients than in CHB patients. In the diagnosis of HCC, the predictive value of SUV39H1 combined with alpha-fetoprotein (AFP) was better than that of AFP alone. CONCLUSION: SUV39H1 is regulated by HBV infection and promotes the proliferation and migration of hepatoma cells by targeting OXPHOS pathway. It indicates that SUV39H1 may be a new biomarker of the diagnosis of HCC.

Relationship of sleep-quality and social-anxiety in patients with breast cancer: a network analysis.

BACKGROUND: There is a complex relationship between social anxiety and sleep quality. However, network analysis studies of associations between social anxiety and sleep quality are lacking, particularly among patients with breast cancer. The current study aimed to extend this research to a sample of patients with breast cancer and to examine symptom-level associations between social anxiety and sleep quality using network analysis. METHODS: Network analysis was conducted to explore their associations and identify bridge items of social anxiety and sleep quality. RESULTS: The network structure revealed 9 important edges between social anxiety and sleep quality. "Subjective sleep quality" had the highest EI value in the network. "Working difficulty under watching" and "Sleep disorders" had the highest BEI values in their own communities. CONCLUSION: There are complex pathological correlation pathways between social anxiety and sleep quality in breast cancer patients. "Subjective sleep quality", "Working difficulty under watching" and "Sleep disorders" have the potential to be intervention targets for sleep disorder-social anxiety comorbidity. Medical staff can take corresponding interventions according to the the centrality indices and bridge centrality indicators identified in this study, which is likely to effectively reduce the comorbidity of sleep disorders and social anxiety.

Physicochemical properties improvement of lycopene by the self-assembly encapsulation of recombinant ferritin GF1 from oyster (Crassostrea gigas).

BACKGROUND: Lycopene (LYC), a carotenoid found abundantly in ripe red fruits of plants, exhibits the highest singlet oxygen quenching activity compared to other carotenoids. Due to its high content of double bonds, the stability of LYC is extremely poor. Herein, the nano-encapsulation strategy based on highly stable marine-derived ferritin GF1 nanocages was tried for improving the thermal stability and oxidation resistance of LYC, thereby boosting its functional activity and industrial application. RESULTS: The preparation of GF1-LYC nanoparticles benefited from the pH-responsive reversible self-assembly of GF1 to capture LYC molecules into GF1 cavity with LYC/protein ratio of 51 to 1. The reassembled GF1 nanocages after encapsulation of LYC maintained intact morphology and good monodispersity. GF1-LYC nanoparticles incorporated the characteristic peak of LYC in the spectrogram, and their powder form contained the crystalline form of LYC. Molecular docking revealed that LYC bound to the inner triple axis channel areas of GF1, interacting with VAL139, LYS72, LYS65, TYR69, PHE129, HIS133, HIS62 and TYR134 amino acids through hydrophobic bonds. Also, fourier transform infrared spectroscopy demonstrated the bonding of GF1 and LYC. Compared to free LYC, GF1 significantly reduced the thermal degradation of encapsulated LYC at 37 °C and maintained the DPPH-scavenging ability of LYC. CONCLUSION: As expected, the water-solubility, thermal stability, and antioxidant capacity of encapsulated LYC from GF1-LYC nanoparticles were notably improved compared to free LYC, indicating the shell-like marine ferritin nanoplatform might enhance the stable delivery of LYC and promote its utilization in the field of food nutrition and industrialization. This article is protected by copyright. All rights reserved.

[Ecological Risk Assessment and Migration and Accumulation Characteristics of Heavy Metals in Farmland Soil-crop System from Typical Pyrite Mining Area].

To evaluate the ecological risk of heavy metals in the soil-crop system in the superimposed high background and human activities from pyrite mining, the heavy metal contents and chemical speciation in soil and crop samples were analyzed, and these data were used to assess the potential ecological risk and factors affecting the migration ability of heavy metals using bioconcentration factors(BCF), potential ecological risk index(RI), risk assessment code(RAC), and correlation analysis. The results indicate that the average Cd, Cu, Pb, and Zn concentrations exceeded the background values of soils in Zhejiang Province and China. Cd had the greatest potential ecological harm, followed by that of Hg. The bioactive components and potential bioactive components of Cd accounted for 46% and 33%, respectively, indicating relatively high bioavailability. Cu and Pb were mainly in potential bioactive components accounting for 60% and 73%, respectively. The As, Cr, Hg, Ni, and Zn were predominantly residual and accounted for >60%, which indicated low biological activity. The RAC levels were in the following order:Cd>Zn>Cu>Pb>Ni>As>Cr>Hg; soil Cd had the highest ecological risk, mainly with high and extremely high levels, whereas other elements had no risk or low risk. Compared with Cd content in soil, only eight rice samples had Cd contents exceeding the safety limit, and sweet potato samples did not exceed the standard. The migration and enrichment capability of rice in order from strong to weak was s follows:Cd>Zn>Cu>Hg>As>Ni>Cr>Pb; the bioactive component of Cd played a significant role in promoting Cd absorption by rice. Soil OM had a bi-directional effect on Cd bioavailability, whereas soil texture had an indirect effect. This comprehensive study shows that the total amount of heavy metals in soil, chemical speciation, biological activities, absorption, and enrichment of heavy metals by crops should be taken into consideration when assessing the ecological risks in the superimposed areas affected by high background and human activities, such as the pyrite mining area.

Mediator Kinase Inhibition Impedes Transcriptional Plasticity and Prevents Resistance to ERK/MAPK-Targeted Therapy in KRAS-Mutant Cancers.

Acquired resistance remains a major challenge for therapies targeting oncogene activated pathways. KRAS is the most frequently mutated oncogene in human cancers, yet strategies targeting its downstream signaling kinases have failed to produce durable treatment responses. Here, we developed multiple models of acquired resistance to dual-mechanism ERK/MAPK inhibitors across KRAS-mutant pancreatic, colorectal, and lung cancers, and then probed the long-term events enabling survival against this class of drugs. These studies revealed that resistance emerges secondary to large-scale transcriptional adaptations that are diverse and cell line-specific. Transcriptional reprogramming extends beyond the well-established early response, and instead represents a dynamic, evolved process that is refined to attain a stably resistant phenotype. Mechanistic and translational studies reveal that resistance to dual-mechanism ERK/MAPK inhibition is broadly susceptible to manipulation of the epigenetic machinery, and that Mediator kinase, in particular, can be co-targeted at a bottleneck point to prevent diverse, cell line-specific resistance programs.

Phytohormone Response of Drought-Acclimated Illicium difengpi (Schisandraceae).

Illicium difengpi (Schisandraceae), which is an endemic, medicinal, and endangered species found in small and isolated populations that inhabit karst mountain areas, has evolved strategies to adapt to arid environments and is thus an excellent material for exploring the mechanisms of tolerance to severe drought. In experiment I, I. difengpi plants were subjected to three soil watering treatments (CK, well-watered treatment at 50% of the dry soil weight for 18 days; DS, drought stress treatment at 10% of the dry soil weight for 18 days; DS-R, drought-rehydration treatment at 10% of the dry soil weight for 15 days followed by rewatering to 50% of the dry soil weight for another 3 days). The effects of the drought and rehydration treatments on leaf succulence, phytohormones, and phytohormonal signal transduction in I. difengpi plants were investigated. In experiment II, exogenous abscisic acid (ABA, 60 mg L-1) and zeatin riboside (ZR, 60 mg L-1) were sprayed onto DS-treated plants to verify the roles of exogenous phytohormones in alleviating drought injury. Leaf succulence showed marked changes in response to the DS and DS-R treatments. The relative concentrations of ABA, methyl jasmonate (MeJA), salicylic acid glucoside (SAG), and cis-zeatin riboside (cZR) were highly correlated with relative leaf succulence. The leaf succulence of drought-treated I. difengpi plants recovered to that observed with the CK treatment after exogenous application of ABA or ZR. Differentially expressed genes involved in biosynthesis and signal transduction of phytohormones (ABA and JA) in response to drought stress were identified by transcriptomic profiling. The current study suggested that the phytohormones ABA, JA, and ZR may play important roles in the response to severe drought and provides a preliminary understanding of the physiological mechanisms involved in phytohormonal regulation in I. difengpi, an endemic, medicinal, and highly drought-tolerant plant found in extremely small populations in the karst region of South China.

Altered anterograde axonal transport of mitochondria in cultured striatal neurons of a knock-in mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive genetic neurodegenerative disease caused by an abnormal expansion of a cytosine-adenine-guanine trinucleotide repeat in the huntingtin gene. One pathological feature of HD is neuronal loss in the striatum. Despite many efforts, mechanisms underlying neuronal loss in HD striatum remain elusive. It was suggested that the mutant huntingtin protein interacts mitochondrial proteins and causes mitochondrial dysfunction in striatal neurons. However, whether axonal transport of mitochondria is altered in HD striatal neurons remains controversial. Here, we examined axonal transport of single mitochondria labelled with Mito-DsRed2 in cultured striatal neurons of zQ175 knock-in mice (a knock-in mouse model of HD). We observed decreased anterograde axonal transport of proximal mitochondria in HD striatal neurons compared with wild-type (WT) striatal neurons. Decreased anterograde transport in HD striatal neurons was prevented by overexpressing mitochondrial Rho GTPase 1 (Miro1). Our results offer a new insight into mechanisms underlying neuronal loss in the striatum in HD.

Chromosome genome assembly and whole genome sequencing of 110 individuals of Conogethes punctiferalis (Guenée).

The yellow peach moth, Conogethes punctiferalis, is a highly polyphagous pest widespread in eastern and southern Asia. It demonstrates a unique ability to adapt to rotten host fruits and displays resistance to pathogenic microorganisms, including fungi. However, the lack of available genomic resources presents a challenge in comprehensively understanding the evolution of its innate immune genes. Here, we report a high-quality chromosome-level reference genome for C. punctiferalis utilizing PacBio HiFi sequencing and Hi-C technology. The genome assembly was 494 Mb in length with a contig N50 of 3.25 Mb. We successfully anchored 1,226 contigs to 31 pseudochromosomes. Our BUSCO analysis further demonstrated a gene coverage completeness of 96.3% in the genome assembly. Approximately 43% repeat sequences and 21,663 protein-coding genes were identified. In addition, we resequenced 110 C. punctiferalis individuals from east China, achieving an average coverage of 18.4 × and identifying 5.8 million high-quality SNPs. This work provides a crucial resource for understanding the evolutionary mechanism of C. punctiferalis' innate immune system and will help in developing new antibacterial drugs.