Current Status of Liverwort Herbaria Specimens and Geographical Distribution in China.

Specimen data play a crucial role in geographical distribution research. In this study, the collection information of liverwort specimens in China was compiled and analyzed to investigate the history, current status, and limitations of liverwort research in China. By utilizing the latest systematic research findings and corresponding environmental data, a niche model was developed to offer theoretical support for exploring the potential geographical distribution and diversity of liverwort resources. A total of 55,427 liverwort specimens were collected in China, resulting in the recording of 1212 species belonging to 169 genera and 63 families. However, there are imbalances in the distributions of liverwort data among different groups, collection units, and geographical areas, with families such as Lejeuneaceae, Porellaceae, and Plagiochilaceae having the highest number of specimens. Similarly, genera such as Porella, Frullania, and Horikawaella were well represented. Remarkably, 125 species had specimen counts exceeding 100. Unfortunately, approximately 51.77% of the species had fewer than 10 recorded specimens. There were four obvious peaks in the collection years of the bryophyte specimens in China, among which the largest collection occurred from 2010 to 2023. Notably, the number of specimens collected at different stages closely aligned with the history of taxonomic research on liverworts in China. The results of the integrity of the liverwort collection indicate that there is insufficient representation of some families and genera, with a concentration of common and widely distributed large families and genera. Tropical and subtropical humid areas are key regions for liverwort diversity, with water and temperature being the primary environmental factors influencing their geographical distribution. The specific temporal and spatial data of species recorded from plant specimens will enhance the study of species diversity, comprehensive protection, and sustainable utilization. Additionally, these data will contribute to the investigation of large-scale biodiversity distribution patterns and the impact of global change on diversity.

Lipidomics revealed alterations in glycerophospholipid metabolism in skin squamous cell carcinoma.

Background: Skin squamous cell carcinoma (SCC) is a prevalent malignancy, and dysregulated lipid metabolism has been implicated in its pathogenesis. However, detailed characterization of lipid alterations in SCC remains limited. Methods: We analyzed lipid metabolic variations in tissue samples from 34 SCC patients and adjacent healthy tissues (located more than 1 cm from the tumor margin) using liquid chromatography-mass spectrometry (LC-MS). Data visualization and discriminatory lipid profiles were identified using principal component analysis (PCA) and sparse partial least squares discriminant analysis (sPLS-DA). Key lipids involved in the SCC metabolism were identified and further validated using an external data set (from a previous study, which similarly explored lipid profiles in oral SCC using lipidomics approaches). Pathway enrichment analysis was conducted to elucidate the metabolic pathways associated with these key lipids. Results: Eight lipids were identified by comparing SCC and healthy tissues including PI(16:0/22:4), PI(18:1/20:4), PE(16:0/20:4), PE(16:0/22:5), PE(16:0/22:6), PE(18:1/20:3), PC(18:1/20:2), and PC(18:2/20:2), as confirmed by independent datasets. All of these lipids were upregulated in SCC tumor tissues. Pathway enrichment analysis revealed significant alterations in glycerophospholipid metabolic pathways, particularly affecting the metabolism of diacylglycerophosphocholines, glycerophosphoethanolamines, and glycerophosphoinositols. Conclusion: Our findings reveal that dysregulated glycerophospholipid metabolism plays a pivotal role in the development of SCC.

Proteomics and its application in the research of acupuncture: An updated review.

As a complementary and alternative therapy, acupuncture is widely used in the prevention and treatment of various diseases. However, the understanding of the mechanism of acupuncture effects is still limited due to the lack of systematic biological validation. Notably, proteomics technologies in the field of acupuncture are rapidly evolving, and these advances are greatly contributing to the research of acupuncture. In this study, we review the progress of proteomics research in analyzing the molecular mechanisms of acupuncture for neurological disorders, pain, circulatory disorders, digestive disorders, and other diseases, with an in-depth discussion around acupoint prescription and acupuncture manipulation modalities. The study found that proteomics has great potential in understanding the mechanisms of acupuncture. This study will help explore the mechanisms of acupuncture from a proteomic perspective and provide information to support future clinical decisions.

The HD-ZIP IV transcription factor GLABRA2 acts as an activator for proanthocyanidin biosynthesis in Medicago truncatula seed coat.

Proanthocyanidins (PAs), a group of flavonoids, are found in leaves, flowers, fruits, and seed coats of many plant species. PAs are primarily composed of epicatechin units in the seed coats of the model legume species, Medicago truncatula. It can be synthesized from two separate pathways, the leucoanthocyanidin reductase (MtLAR) pathway and the anthocyanidin synthase (MtANS) pathway, which produce epicatechin through anthocyanidin reductase (MtANR). These pathways are mainly controlled by the MYB-bHLH-WD40 (MBW) ternary complex. Here, we characterize a class IV homeodomain-leucine zipper (HD-ZIP IV) transcription factor, GLABRA2 (MtGL2), which contributes to PA biosynthesis in the seed coat of M. truncatula. Null mutation of MtGL2 results in dark brown seed coat, which is accompanied by reduced PAs accumulation and increased anthocyanins content. The MtGL2 gene is predominantly expressed in the seed coat during the early stages of seed development. Genetic and molecular analyses indicate that MtGL2 positively regulates PA biosynthesis by directly activating the expression of MtANR. Additionally, our results show that MtGL2 is strongly induced by the MBW activator complexes that are involved in PA biosynthesis. Taken together, our results suggest that MtGL2 acts as a novel positive regulator in PA biosynthesis, expanding the regulatory network and providing insights for genetic engineering of PA production.

Polyvinyl chloride and polybutylene adipate microplastics affect peanut and rhizobium symbiosis by interfering with multiple metabolic pathways.

Microplastics (MPs), widely presented in cultivated soil, have caused serious stresses on crop growth. However, the mechanism by which MPs affect legumes and rhizobia symbiosis is still unclear. Here, peanut seedlings were inoculated with Bradyrhizobium zhanjiangense CCBAU 51778 and were grown in vermiculite with 3 %/5 % (w/w) addition of PVC (polyvinyl chloride)-MPs/PBAT (polybutylene adipate)-MPs. PVC-MPs and PBAT-MPs separately decreased nodule number by 33-100 % and 2.62-80.91 %. Transcriptome analysis showed that PVC-MPs affected more DEGs (differentially expressed genes) than PBAT-MPs, indicating PVC-MPs were more devastating for the symbiosis than PBAT-MPs. Functional annotation revealed that PVC-MPs and PBAT-MPs enriched DEGs related to biosynthesis pathways such as flavonoid, isoflavonoid, and phenylpropanoid, in peanut. And when the dose increased from 3 % to 5 %, PVC-MPs mainly enriched the pathways of starch and sucrose metabolism, alanine, aspartate and glutamate metabolism, diterpenoid biosynthesis, etc.; PBAT-MPs enriched cysteine and methionine metabolism, photosynthesis, MAPK signaling, and other pathways. These significantly enriched pathways functioned in reducing nodule number and promoting peanut tolerance to MPs stresses. This study reveals the effect of PVC-MPs and PBAT-MPs on peanut and rhizobium symbiosis, and provides new perspectives for legume production and environmental safety.

ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2-BECN1 interaction.

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two neurodegenerative disorders. The GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72 (C9orf72) is the most genetic cause of both ALS and FTD. According to the previous studies, GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation, which produces dipeptide repeat (DPR) proteins. Although there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD, whether these DPRs can affect autophagy remains unclear. In the present study, we find that poly-GR and poly-PR, two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies, strongly inhibit starvation-induced autophagy. Moreover, our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation, therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in cells. Importantly, our study not only highlights the role of C9orf72 DPR in autophagy dysfunction, but also provides novel insight that pharmacological intervention of autophagy using SW063058, a small molecule compound that can disrupt the interaction between BECN1 and BCL2, may reduce C9orf72 DPR-induced neurotoxicity.

Exogenous Melatonin Enhances Dihydrochalcone Accumulation in Lithocarpus litseifolius Leaves via Regulating Hormonal Crosstalk and Transcriptional Profiling.

Dihydrochalcones (DHCs) constitute a specific class of flavonoids widely known for their various health-related advantages. Melatonin (MLT) has received attention worldwide as a master regulator in plants, but its roles in DHC accumulation remain unclear. Herein, the elicitation impacts of MLT on DHC biosynthesis were examined in Lithocarpus litseifolius, a valuable medicinal plant famous for its sweet flavor and anti-diabetes effect. Compared to the control, the foliar application of MLT significantly increased total flavonoid and DHC (phlorizin, trilobatin, and phloretin) levels in L. litseifolius leaves, especially when 100 µM MLT was utilized for 14 days. Moreover, antioxidant enzyme activities were boosted after MLT treatments, resulting in a decrease in the levels of intracellular reactive oxygen species. Remarkably, MLT triggered the biosynthesis of numerous phytohormones linked to secondary metabolism (salicylic acid, methyl jasmonic acid (MeJA), and ethylene), while reducing free JA contents in L. litseifolius. Additionally, the flavonoid biosynthetic enzyme activities were enhanced by the MLT in leaves. Multiple differentially expressed genes (DEGs) in RNA-seq might play a crucial role in MLT-elicited pathways, particularly those associated with the antioxidant system (SOD, CAT, and POD), transcription factor regulation (MYBs and bHLHs), and DHC metabolism (4CL, C4H, UGT71K1, and UGT88A1). As a result, MLT enhanced DHC accumulation in L. litseifolius leaves, primarily by modulating the antioxidant activity and co-regulating the physiological, hormonal, and transcriptional pathways of DHC metabolism.

Attention pyramid pooling network for artificial diagnosis on pulmonary nodules.

The development of automated tools using advanced technologies like deep learning holds great promise for improving the accuracy of lung nodule classification in computed tomography (CT) imaging, ultimately reducing lung cancer mortality rates. However, lung nodules can be difficult to detect and classify, from CT images since different imaging modalities may provide varying levels of detail and clarity. Besides, the existing convolutional neural network may struggle to detect nodules that are small or located in difficult-to-detect regions of the lung. Therefore, the attention pyramid pooling network (APPN) is proposed to identify and classify lung nodules. First, a strong feature extractor, named vgg16, is used to obtain features from CT images. Then, the attention primary pyramid module is proposed by combining the attention mechanism and pyramid pooling module, which allows for the fusion of features at different scales and focuses on the most important features for nodule classification. Finally, we use the gated spatial memory technique to decode the general features, which is able to extract more accurate features for classifying lung nodules. The experimental results on the LIDC-IDRI dataset show that the APPN can achieve highly accurate and effective for classifying lung nodules, with sensitivity of 87.59%, specificity of 90.46%, accuracy of 88.47%, positive predictive value of 95.41%, negative predictive value of 76.29% and area under receiver operating characteristic curve of 0.914.

Objectivization study of acupuncture Deqi and brain modulation mechanisms: a review.

Deqi is an important prerequisite for acupuncture to achieve optimal efficacy. Chinese medicine has long been concerned with the relationship between Deqi and the clinical efficacy of acupuncture. However, the underlying mechanisms of Deqi are complex and there is a lack of systematic summaries of objective quantitative studies of Deqi. Acupuncture Deqi can achieve the purpose of treating diseases by regulating the interaction of local and neighboring acupoints, brain centers, and target organs. At local and neighboring acupoints, Deqi can change their tissue structure, temperature, blood perfusion, energy metabolism, and electrophysiological indicators. At the central brain level, Deqi can activate the brain regions of the thalamus, parahippocampal gyrus, postcentral gyrus, insular, middle temporal gyrus, cingulate gyrus, etc. It also has extensive effects on the limbic-paralimbic-neocortical-network and default mode network. The brain mechanisms of Deqi vary depending on the acupuncture techniques and points chosen. In addition, Deqi 's mechanism of action involves correcting abnormalities in target organs. The mechanisms of acupuncture Deqi are multi-targeted and multi-layered. The biological mechanisms of Deqi are closely related to brain centers. This study will help to explore the mechanism of Deqi from a local-central-target-organ perspective and provide information for future clinical decision-making.

Rewiring of a KNOXI regulatory network mediated by UFO underlies the compound leaf development in Medicago truncatula.

Class I KNOTTED-like homeobox (KNOXI) genes are parts of the regulatory network that control the evolutionary diversification of leaf morphology. Their specific spatiotemporal expression patterns in developing leaves correlate with the degrees of leaf complexity between simple-leafed and compound-leafed species. However, KNOXI genes are not involved in compound leaf formation in several legume species. Here, we identify a pathway for dual repression of MtKNOXI function in Medicago truncatula. PINNATE-LIKE PENTAFOLIATA1 (PINNA1) represses the expression of MtKNOXI, while PINNA1 interacts with MtKNOXI and sequesters it to the cytoplasm. Further investigations reveal that UNUSUAL FLORAL ORGANS (MtUFO) is the direct target of MtKNOXI, and mediates the transition from trifoliate to pinnate-like pentafoliate leaves. These data suggest a new layer of regulation for morphological diversity in compound-leafed species, in which the conserved regulators of floral development, MtUFO, and leaf development, MtKNOXI, are involved in variation of pinnate-like compound leaves in M. truncatula.

Chinese patent medicine as a complementary and alternative therapy for type 2 diabetes mellitus: A scoping review.

OBJECTIVE: This scoping review aims to document Chinese Patent Medicines (CPMs) for Type 2 Diabetes Mellitus, explore whether CPMs can improve patients' health outcomes, and set priorities in addressing research gaps in this area. METHODS: Following the framework of PRISMA-SCr, we proposed the research questions based on PICOS principle, and searched the CPMs for T2DM from three drug lists, followed by a systematic search of the literature in eight databases from their inception to June 22, 2023. Then, we developed the eligibility criteria and systematically reviewed the relevant studies, retained the studies about CPMs for T2DM, extracted the related data, and identified the differences across studies in structured charts. RESULTS: A total of 25 types of CPMs were extracted from the three drug lists. Radix astragali appeared most frequently (19 times) among the herbal medicinal ingredients of CPMs. A total of 449 articles were included in the full-paper analysis ultimately, all of which were about 20 types of CPMs, and there were no related reports on the remaining five CPMs. Except about a quarter (25.39 %, 114/449) using CPMs alone, the remaining studies all involved the combination with oral hypoglycemics for T2DM. Biguanides are the most common drugs used in combination with CPMs (50.14 %, 168/335). Fasting plasma glucose (FPG) is the most frequently reported outcomes in efficacy evaluation (82.41 %, 370/449). CONCLUSION: There are a total of 25 types of CPMs currently available for T2DM patients. However, the volume of related evidence on these CPMs varies. It is necessary to standardize the combined use of CPMs and conventional medicine and select appropriate outcomes in future studies.

Isolation, characterization, and phylogenetic analysis of two new porcine parvovirus 1 isolates from Northern China.

Porcine parvovirus (PPV) is a pathogen of infectious reproductive disease, which can cause stillbirth, mummification, embryo death, and infertility (SMEDI) syndrome in pigs. The objective of this study was to gain new insights into the evolution and phylogeny of the PPV1 genome. In this study, we isolated two new PPV1 (HLJ202108-Y and SDLC202109) from northern China and sequenced their whole genomes. The new isolates were found to have three amino acid substitutions (K195R, K562R, and S578P) in nonstructural protein 1. The VP2 amino acid site contained nine nonsynonymous substitutions, including six substitutions of the Kresse strain corresponding to the NADL-2 strain and three substitutions of A414S, S436T, and N555K. Genetic evolution analysis was conducted on 107 reference sequences available in the GenBank database, and 4-5 PPV1 taxa were defined. The new isolates were in the same phylogenetic cluster as strain 27a. The changes in the cluster, specifically marker amino acids, and their potential role in enhancing pathogenicity are discussed in this study. Furthermore, the evolutionary tree map results showed that the strains in China were evolving in two directions: one was becoming increasingly similar to early NADL-2 strains, while the other was evolving toward 27a-like strains. We also compared the proliferation ability of the isolated strains in susceptible cells by analyzing the multistep growth curves. The results showed that the virulence titer of the mutant strain was high. In summary, this study introduced the latest changes in PPV and discussed the virus characteristics that were considered to affect virulence.

A high rain-erosion resistant bio-based nanogel with continuous immunity induction for plant virus inhibition.

Tobacco mosaic virus (TMV) is the most widely spread and harmful virus in the world, causing serious economic losses annually. However, the low anti-erosion ability of the pesticides for TMV management make it easy to be washed by the rain, which makes the effective duration of the pesticides shorter. In this paper, a new bio-based nanogel with superior antiviral activity was reported, and its slow-release behavior, rain erosion resistance and the antiviral mechanism was systematically studied. The results determined that the nanogels (Zn2+@ALGNP and Zn2+@ALGNP@PL) exhibited sustained releasing of Zn2+ with a 7 days duration, and the ε-PL coating could enhance the releasing rate of Zn2+. Moreover, Zn2+@ALGNP@PL displayed a lower contact angle, indicating greater adhesion to the leaf surface, and in consequence imposed better resistance to simulate rain erosion than pure Zn2+. Strikingly, Zn2+@ALGNP@PL could inhibit plant virus infection by aggregating the virions and reducing its coat protein stability, as well as inducing the efficient expression of reactive oxygen species, antioxidant enzymes and resistance genes to enhance plant resistance and promote plant growth. Overall, this study had successfully developed a high rain-erosion resistant bio-based nanogel capable of continue to induce resistant plants and promote plant growth.

Effect of electroacupuncture at the acupoints for Tiaozang Xingshen on cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction. / "调脏醒神"电针对2åž‹ç³–å°¿ç— ç›¸å ³è®¤çŸ¥åŠŸèƒ½éšœç¢æ‚£è€ è„‘å† ä»£è°¢çš„å½±å“.

OBJECTIVES: To investigate the cerebral metabolism in the patients with type 2 diabetes mellitus-associated cognitive dysfunction (T2DACD) and explore the mechanism of electroacupuncture (EA) at the acupoints for Tiaozang Xingshen (adjusting zangfu function and rescuing the spirit) in treatment of T2DACD, using magnetic resonance spectroscopy. METHODS: Fifteen patients with T2DACD (observation group) and 22 healthy subjects (control group) were enrolled. In the observation group, the patients were treated with EA for Tiaozang Xingshen at Baihui (GV 20) and Shenting (GV 24), and bilateral Feishu (BL 13), Pishu (BL 20), Shenshu (BL 23), Zusanli (ST 36), Sanyinjiao (SP 6), Hegu (LI 4) and Taichong (LR 3). EA was operated with disperse-dense wave, 2 Hz/100 Hz in frequency and 0.1 mA to 1.0 mA in current intensity; 30 min each time, once daily. One course of EA consisted of 5 treatments, at the interval of 2 days and the intervention lasted 8 courses. Before treatment in the control group, before and after treatment in the observation group, the score of Montreal cognitive assessment scale (MoCA), the score of clinical dementia rating (CDR), Flanker paradigm, Stroop paradigm, Nback paradigm, the score of self-rating anxiety scale (SAS), the score of self-rating depression scale (SDS), and the score of Hamilton depression rating scale (HAMD) were evaluated separately; the glycolipid metabolic indexes (fasting plasma glucose [FPG], glycosylated hemoglobin type A1c [HbA1c], total cholesterol [TC], triacylglycerol [TG], high-density lipoprotein cholesterol [HDL-C] and low-density lipoprotein cholesterol [LDL-C]) were determined；with the magnetic resonance spectroscopy technique adopted, the metabolites in the basal ganglia area were detected. The correlation analysis was performed for the metabolite values with MoCA score, CDR score , Flanker paradigm, Stroop paradigm, and Nback paradigm. RESULTS: Before treatment, compared with the control group, in the observation group, MoCA score was lower (P<0.001), CDR score and the levels of FPG and HbA1c were higher (P<0.001); the reaction times of Flanker non-conflict, Flanker conflict, Stroop neutrality, Stroop congruence, Stroop conflict, and 1-back were prolonged (P<0.05, P<0.001), and the accuracy of Flanker conflict, Stroop conflict, and 1-back decreased (P<0.05, P<0.01); the ratio of N-acetyl aspartate (NAA) to creatine (Cr) in the left basal ganglia area was dropped (P<0.001), and that of myo-inositol (MI) to Cr in the right side increased (P<0.05). In the observation group after treatment, compared with the levels before treatment, MoCA score was higher (P<0.001), the scores of CDR, SAS and HAMD were reduced (P<0.01, P<0.05), the reaction times of Flanker conflict and Stroop conflict shortened (P<0.001, P<0.05), and the accuracy of Flanker conflict and 1-back increased (P<0.001, P<0.05); the ratio of NAA to Cr in the left basal ganglia area and that of the gamma-aminobutyric acid (GABA) to Cr in the right increased (P<0.05), that of MI to Cr in the right decreased (P<0.05). Before treatment, in the observation group, the ratio of MI to Cr in the right basal ganglia area was positively correlated with the reaction time of Stroop congruence (r=0.671, P=0.012) and this ratio was positively correlated with the reaction time of Stroop conflict (r=0.576, P=0.039). CONCLUSIONS: Electroacupuncture for "adjusting zangfu function and rescuing the mind" improves the cognitive function of T2DACD patients, which may be related to the regulation of NAA, MI and GABA levels in the basal ganglia.

Acupuncture combined with Tuina in the treatment of cervical longus tendinitis: A case report.

INTRODUCTION: Cervical longus tendonitis is a type of disease with neck pain as the main clinical manifestation. Because the front of the cervical longus muscle is adjacent to the esophagus and pharynx, this disease is often accompanied by pharyngeal pain and pain when swallowing. Clinical and imaging doctors often have an incomplete understanding of it, and this disease is often confused with other diseases that cause neck pain. PATIENT CONCERNS: A 33-year-old Chinese woman was the patient. Suffering from severe neck pain and significantly limited activity, accompanied by left shoulder pain, occasionally dizziness, headache and other symptoms, the pain is significantly aggravated when doing swallowing action. DIAGNOSIS: Tendonitis of the long neck muscle. INTERVENTIONS: Given the patient's condition, we used acupuncture combined with massage therapy as a symptomatic treatment. OUTCOMES: After 10 days of treatment, the symptoms were better than before, and no pain was seen in the swallowing movements such as drinking water (Fig. 2C and D). LESSONS: Because the clinical reports of diseases are rare, the treatment methods are limited, and acupuncture combined with massage is an effective method for the treatment of tendonitis of the cervical long muscle, to dredge the meridians, promoting blood circulation, removing blood stasis and relieving pain.

Acupuncture is an effective therapy for macular damage: A case report.

RATIONALE: Many factors can contribute to the development of macular injury, which results in vision loss as a result of a disease. Heredity, age, underlying eye illness, internal eye surgery, or eye trauma can all cause it. A safer alternative to current therapies for macular degeneration is urgently needed since they all induce ocular irritation and postoperative recurrence as well as a host of other adverse effects. PATIENT CONCERNS: A 12-year-old girl was the patient. A laser pen burnt her right eye. There was a spot and a shadow in the middle of her right eye's visual field. DIAGNOSES: Macular degeneration. INTERVENTIONS: Given the patient's age, we opted out of medicine and instead used acupuncture as a symptomatic treatment. OUTCOMES: Two months after therapy concluded, optical coherence tomography result report indicate that the macula region of the right eye is better than it was previously. The corrected visual acuity of the right eye recovered from 0.25 to 1.0, and the clinical accompanying symptoms of the right eye disappeared. LESSONS: No additional medication or surgical procedure was employed in this instance. We treated the macular damage with acupuncture, which relieved the patient's clinical symptoms and had no adverse effects. This demonstrates that acupuncture may be beneficial in treating ophthalmopathy in this direction.

Metabolomics profiling in predicting of post-herpetic neuralgia induced by varicella zoster.

To explore potential metabolomics biomarkers in predicting post-herpetic neuralgia (PHN) induced by herpes zoster (HZ). A total of 90 eligible patients were prospectively enrolled and assigned into an acute pain (ACP) group and a PHN group. Serum samples were collected before clinical intervention to perform metabolomics profiling analyses using gas chromatography mass spectrometry (GC-MS). Key metabolites were identified using partial least squares discriminant analysis (PLS-DA). A binary logistic regression was used to build a combined biomarker model to predict PHN from ACP. The discriminating efficiency of the combined biomarker model was investigated and validated by internal validation. Six metabolites were identified as the key metabolites related to PHN. All these metabolites (N-Acetyl-5-hydroxytryptaMine, glucose, dehydroascorbic acid, isopropyl-beta-D-thiogalactopyranoside, 1,5-anhydro-D-sorbitol, and glutamic acid) were found elevated in the PHN group. Pathway analyses showed that glucose-alanine cycle, tryptophan metabolism, tyrosine metabolism, lactose degradation, malate-aspartate shuttle were top five metabolic pathways evolved in PHN. The AUC was 0.85 (95% CI 0.76-0.93) for the combined biomarker model, and was 0.91 (95% CI 0.84-1.00) for the internal validation data set to predict PHN. Metabolomics analyses of key metabolites could be used to predict PHN induced by HZ.

Chlorpromazine affects autophagy in association with altered Rag GTPase-mTORC1-TFEB signaling.

Autophagy is a critical protein and organelle quality control system, which regulates cellular homeostasis and survival. Growing pieces of evidence suggest that autophagic dysfunction is strongly associated with many human diseases, including neurological diseases and cancer. Among various autophagic regulators, microphthalmia (MiT)/TFE transcription factors, including transcription factor EB (TFEB), have been shown to act as the master regulators of autophagosome and lysosome biogenesis in both physiological and pathological conditions. According to the previous studies, chlorpromazine (CPZ), an FDA-approved antipsychotic drug, affects autophagy in diverse cell lines, but the underlying mechanism remains elusive. In our present study, we find that CPZ treatment induces TFEB nuclear translocation through Rag GTPases, the upstream regulators of mechanistic target of rapamycin complex 1 (mTORC1) signaling. Meanwhile, CPZ treatment also blocks autophagosome-lysosome fusion. Notably, we find a significant accumulation of immature autophagosome vesicles in CPZ-treated cells, which may impede cellular homeostasis due to the dysfunction of the autophagy-lysosome pathway. Interestingly and importantly, our data suggest that the expression of the active form of Rag GTPase heterodimers helps in reducing the accumulation of autophagosomes in CPZ-treated cells, further suggesting a major contribution of the Rag GTPase-mTORC1-TFEB signaling axis in CPZ-induced autophagic impairment.

UBQLN2 and HSP70 participate in Parkin-mediated mitophagy by facilitating outer mitochondrial membrane rupture.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two aging-related neurodegenerative diseases that share common key features, including aggregation of pathogenic proteins, dysfunction of mitochondria, and impairment of autophagy. Mutations in ubiquilin 2 (UBQLN2), a shuttle protein in the ubiquitin-proteasome system (UPS), can cause ALS/FTD, but the mechanism underlying UBQLN2-mediated pathogenesis is still uncertain. Recent studies indicate that mitophagy, a selective form of autophagy which is crucial for mitochondrial quality control, is tightly associated with neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and ALS. In this study, we show that after Parkin-dependent ubiquitination of damaged mitochondria, UBQLN2 is recruited to poly-ubiquitinated mitochondria through the UBA domain. UBQLN2 cooperates with the chaperone HSP70 to promote UPS-driven degradation of outer mitochondrial membrane (OMM) proteins. The resulting rupture of the OMM triggers the autophagosomal recognition of the inner mitochondrial membrane receptor PHB2. UBQLN2 is required for Parkin-mediated mitophagy and neuronal survival upon mitochondrial damage, and the ALS/FTD pathogenic mutations in UBQLN2 impair mitophagy in primary cultured neurons. Taken together, our findings link dysfunctional mitophagy to UBQLN2-mediated neurodegeneration.

Cell-type-specific CRISPRization of mitochondrial DNA using bifunctional biodegradable silica nanoparticles.

We report cell-type-specific and CRISPR/Cas9-mediated mtDNA editing platform by using bifunctional biodegradable silica nanoparticles, which were capable of selective intracellular delivery to CD44-overexpressed cells and subsequent mitochondrial localization, followed by glutathione-responsive biodegradation and release of Cas9/sgRNA to realize precise mtDNA editing.