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Abstract Biallelic mutations in the coenzyme Q7 (COQ7) encoding gene were recently identified as a genetic cause of distal hereditary motor neuropathy. Here, we explored the clinical, electrophysiological, pathological, and genetic characteristics of a Chinese patient with spastic paraplegia associated with recessive variants in COQ7. This patient carried a novel c.322C>A (p.Pro108Thr) homozygous variant. Sural biopsy revealed mild mixed axonal and demyelinating degeneration. Immunoblotting showed a significant decrease in the COQ7 protein level in the patient's fibroblasts. This study confirmed that COQ7 variant as a genetic cause of HSP, and further extended spastic paraplegia to the phenotypic spectrum of COQ7‐related disorders.

ABSTRACTMyotonia congenita (MC) is a rare hereditary muscle disease caused by variants in the CLCN1 gene. Currently, the correlation of phenotype-genotype is still uncertain between dominant-type Thomsen (TMC) and recessive-type Becker (BMC). The clinical data and auxiliary examinations of MC patients in our clinic were retrospectively collected. Electromyography was performed in 11 patients and available family members. Whole exome sequencing was conducted in all patients. The clinical and laboratory data of Chinese MC patients reported from June 2004 to December 2022 were reviewed. A total of 11 MC patients were included in the study, with a mean onset age of 12.64 ± 2.73 years. The main symptom was muscle stiffness of limbs. Warm-up phenomenon and percussion myotonia were found in all patients. Electromyogram revealed significant myotonic charges in all patients and two asymptomatic carriers, while muscle MRI and biopsy showed normal or nonspecific changes. Fourteen genetic variants including 6 novel variants were found in CLCN1. Ninety-eight Chinese patients were re-analyzed and re-summarized in this study. There were no significant differences in the demographic data, clinical characteristics, and laboratory findings between 52 TMC and 46 BMC patients. Among the 145 variants in CLCN1, some variants, including the most common variant c.892 G>A, could cause TMC in some families and BMC in others. This study expanded the clinical and genetic spectrum of Chinese patients with MC. It was difficult to distinguish between TMC and BMC only based on the clinical, laboratory, and genetic characteristics.

BackgroundLAMA2-related limb girdle muscular dystrophy (LGMD R23) is rare. The detailed clinical phenotypes and genetic information associated with LGMD R23 are unknown.MethodsWe conducted a retrospective cross-sectional and longitudinal study on 19 LGMD R23 patients.ResultsNormal early motor development was observed in 84.2% patients. Mild orthopedic complications were observed in 42.1% patients. 36.8% patients had seizures, which is unusually frequent in LGMD. Epilepsy was eventually diagnosed in 26.3% patients. 46.7% patients presented with motor neuropathy. Genetic analysis identified 29 pathogenic variants, with missense and frameshift variants being the most common. The mutant sites were mainly distributed in the N-terminal and G-like domains of laminin. The missense variants are distributed near the N-terminus (exons 3–11), whereas frameshift variants are distributed in exons 12–65. Five patients were diagnosed with epilepsy and all of them harbor at least one missense variants in exon 4. 71.4% variants of patients with motor neuropathy located in the LN domain.ConclusionsMissense variants in exon 4 maybe correlated with epilepsy and variants in the LN domain maybe correlated with motor neuropathy in Chinese patients. Our study expands the clinical and genetic spectrum caused by LAMA2 variations and provides novel genotype-phenotype correlations of LGMD R23.

IntroductionCerebral sparganosis is a rare parasitic infection of the brain tissue. The remission of MRI change and clinical symptom has been used to evaluate the therapeutic effect. However, there is no study to correlate the serum IgG antibody level of sparganum to the prognosis of disease after treatment. Methods87 patients with cerebral sparganosis were collected from three medical centers. Clinical symptoms and MRI changes were evaluated at 12 months after initial treatment, and serum IgG antibody level of sparganum was evaluated at 2, 6, and 12 months after treatment. The positive cut-off value was based on 2.1 times the optical density (OD) of negative control. The index value was defined as the sample OD divided by the cut-off value.ResultsAmong the 87 patients after treatment, 71 patients had good clinical outcomes, and 16 had poor clinical outcomes. The area under the curve (AUC) showed that the index value measured at 12 months after treatment had the best prediction effect, with a value of 2.014. In the good-outcome group, the index values were less than 2.014 in all 71 patients, and only 8 patients had mildly enhanced residual lesions on MRI. In the poor-outcome group, the index values were more than 2.014 in all 16 patients, and all patients still showed significantly enhanced lesions on MRI. Compared with poor-outcome patients, only 2 patients with good outcomes had disease recurrence after treatment.DiscussionThis study provided evidence that the serum IgG antibody level of sparganum was a promising biomarker to evaluate the prognosis of patients with cerebral sparganosis after treatment.

Abstract Background LAMA2-related muscular dystrophy including LAMA2-related congenital muscular dystrophy (LAMA2-CMD) and autosomal recessive limb-girdle muscular dystrophy-23 (LGMDR23) is caused by LAMA2 pathogenic variants. We aimed to describe the natural history and establish genotype–phenotype correlations in a large cohort of Chinese patients with LAMA2-related muscular dystrophy. Methods Clinical and genetic data of LAMA2-related muscular dystrophy patients enrolled from ten research centers between January 2003 and March 2021 were collected and analyzed. Results One hundred and thirty patients (116 LAMA2-CMD and 14 LGMDR23) were included. LAMA2-CMD group had earlier onset than LGMDR23 group. Head control, independent sitting and ambulation were achieved in 76.3%, 92.6% and 18.4% of LAMA2-CMD patients at median ages of 6.0 months (range 2.0–36.0 months), 11.0 months (range 6.0–36.0 months), and 27.0 months (range 18.0–84.0 months), respectively. All LGMDR23 patients achieved independent ambulation at median age of 18.0 months (range 13.0–20.0 months). Motor regression in LAMA2-CMD mainly occurred concurrently with rapid progression of contractures during 6–9 years old. Twenty-four LAMA2-related muscular dystrophy patients died, mostly due to severe pneumonia. Seizures occurred in 35.7% of LGMDR23 and 9.5% of LAMA2-CMD patients. Forty-six novel and 97 known LAMA2 disease-causing variants were identified. The top three high-frequency disease-causing variants in Han Chinese patients were c.7147C > T (p.R2383*), exon 4 deletion, and c.5156_5159del (p.K1719Rfs*5). In LAMA2-CMD, splicing variants tended to be associated with a relatively mild phenotype. Nonsense variants were more frequent in LAMA2-CMD (56.9%, 66/116) than in LGMDR23 (21.4%, 3/14), while missense disease-causing variants were more frequent in LGMDR23 (71.4%, 10/14) than in LAMA2-CMD (12.9%, 15/116). Copy number variations were identified in 26.4% of survivors and 50.0% of nonsurvivors, suggesting that copy number variations were associated with lower rate of survival (p = 0.029). Conclusions This study provides better understandings of natural history and genotype–phenotype correlations in LAMA2-related muscular dystrophy, and supports therapeutic targets for future researches.

Wallerian degeneration occurs after peripheral nerve injury and provides a beneficial microenvironment for nerve regeneration. Our previous study demonstrated that ascorbic acid promotes peripheral nerve regeneration, possibly through promoting Schwann cell proliferation and phagocytosis and enhancing macrophage proliferation, migration, and phagocytosis. Because Schwann cells and macrophages are the main cells involved in Wallerian degeneration, we speculated that ascorbic acid may accelerate this degenerative process. To test this hypothesis, 400 mg/kg ascorbic acid was administered intragastrically immediately after sciatic nerve transection, and 200 mg/kg ascorbic acid was then administered intragastrically every day. In addition, rat sciatic nerve explants were treated with 200 μM ascorbic acid. Ascorbic acid significantly accelerated the degradation of myelin basic protein-positive myelin and neurofilament 200-positive axons in both the transected nerves and nerve explants. Furthermore, ascorbic acid inhibited myelin-associated glycoprotein expression, increased c-Jun expression in Schwann cells, and increased both the number of macrophages and the amount of myelin fragments in the macrophages. These findings suggest that ascorbic acid accelerates Wallerian degeneration by accelerating the degeneration of axons and myelin in the injured nerve, promoting the dedifferentiation of Schwann cells, and enhancing macrophage recruitment and phagocytosis. The study was approved by the Southern Medical University Animal Care and Use Committee (approval No. SMU-L2015081) on October 15, 2015.

Abstract Objective To identify a new genetic cause in patients segregating distal hereditary motor neuropathy (dHMN) with an autosomal recessive pattern. Methods Whole‐exome sequencing was conducted in two siblings and was combined with segregation analysis. Additionally, 83 unrelated dHMN patients with unknown genetic cause were screened. RNA analysis was performed using blood lymphocytes and HEK293 cells transfected with mutant plasmids. Immunohistochemistry and Western blot analysis was applied to the nerve tissue. The enzymatic activities of mutant proteins were measured in the cultured cells to verify the pathogenicity of variants. Results The clinical features of the patients showed late‐onset phenotype of distal motor neuropathy without sensory involvement. We identified that compound heterozygous variants of c.1342C>T and c.2071_2072delGCinsTT in the membrane metalloendopeptidase (MME) gene co‐segregated with the phenotype in a dHMN family. In an additional group of 83 patients with dHMN, compound heterozygous variants of c.1416+2T>C and c.2027C>T in MME were identified in one patient. The splice site variant c.1416+2T>C results in skipping of exon 13. The stop variant c.1342C>T induces mRNA degradation via nonsense‐mediated mRNA decay. Transcript levels of MME in the lymphocytes showed no significant differences between the patients and controls. We also identified that MME variants were associated with mild decrease in protein expression in the sural nerve and significant impairments of enzymatic activity. Interpretation Variants in the MME gene were associated with not only a Charcot‐Marie‐Tooth neuropathy phenotype but also with an autosomal‐recessive dHMN phenotype. Loss of function may play a role in the pathogenesis of dHMN.

Ascorbic acid (AA) is an essential micronutrient that has been safely used in the clinic for many years. The present study indicates that AA has an unexpected function in facilitating nerve regeneration. Using a mouse model of sciatic nerve crush injury, we found that AA can significantly accelerate axonal regrowth in the early stage [3 days post-injury (dpi)], a finding that was revealed by immunostaining and Western blotting for antibodies against GAP-43 and SCG10. On day 28 post-injury, histomorphometric assessments demonstrated that AA treatment increased the density, size, and remyelination of regenerated axons in the injured nerve and alleviated myoatrophy in the gastrocnemius. Moreover, the results from various behavioral tests and electrophysiological assays revealed that nerve injury-derived functional defects in motor and sensory behavior as well as in nerve conduction were significantly attenuated by treatment with AA. The potential mechanisms of AA in nerve regeneration were further explored by investigating the effects of AA on three types of cells involved in this process [neurons, Schwann cells (SCs) and macrophages] through a series of experiments. Overall, the data illustrated that AA treatment in cultured dorsal root ganglionic neurons resulted in increased neurite growth and lower expression of RhoA, which is an important inhibitory factor in neural regeneration. In SCs, proliferation, phagocytosis, and neurotrophin expression were all enhanced by AA. Meanwhile, AA treatment also improved proliferation, migration, phagocytosis, and anti-inflammatory polarization in macrophages. In conclusion, this study demonstrated that treatment with AA can promote the morphological and functional recovery of injured peripheral nerves and that this effect is potentially due to AA’s bioeffects on neurons, SCs and macrophages, three of most important types of cells involved in nerve injury and regeneration.

RhoA-GTPase (RhoA) is widely regarded as a key molecular switch to inhibit neurite outgrowth by rigidifying the actin cytoskeleton. However, during neurite outgrowth, whether and how microtubule dynamics are regulated by RhoA remains to be elucidated. Herein, CT04 and Y27632 were used to inactivate RhoA and its downstream effector Rho-associated coiled coil-forming kinase (ROCK), while the RhoAQ63L lentiviral vector was utilized to overexpress the constitutively activated RhoA in dorsal root ganglion (DRG) neurons or neuronal differentiated PC12 cells. The current data illustrate that the RhoA signaling pathway negatively modulates neurite outgrowth and elevates the expression of Glu-tubulin (a marker for a stabilized microtubule). Meanwhile, the microtubule-severing proteins spastin and p60-katanin were downregulated by the RhoA signaling pathway. When spastin and p60-katanin were knocked down, the effects of RhoA inhibition on neurite outgrowth were significantly reversed. Taken together, this study demonstrates that the RhoA pathway-mediated inhibition of neurite outgrowth is not only related to the modulation of microfilament dynamics but is also attributable to the regulation of the expression of spastin and p60-katanin and thus influences microtubule dynamics.

Inhibiting RhoA-subfamily GTPases by C3 transferase is widely recognized as a prospective strategy to enhance axonal regeneration. When C3 transferase is administered for treating the injured peripheral nerves, Schwann cells (SCs, important glial cells in peripheral nerve) are inevitably impacted and therefore SC bioeffects on nerve regeneration might be influenced. However, the potential role of C3 transferase on SCs remains elusive. Assessed by cell counting, EdU and water-soluble tetrazolium salt-1 (WST-1) assays as well as western blotting with PCNA antibody, herein we first found that CT04 (a cell permeable C3 transferase) treatment could significantly suppress SC proliferation. Unexpectedly, using Y27632 to inhibit ROCK (the well-accepted downstream signal molecule of RhoA subfamily) did not impact SC proliferation. Further studies indicated that CT04 could inactivate AKT pathway by altering the expression levels of phosphorylated AKT (p-AKT), PI3K and PTEN, while activating AKT pathway by IGF-1 or SC79 could reverse the inhibitory effect of CT04 on SC proliferation. Based on present data, we concluded that inhibition of RhoA-subfamily GTPases could suppress SC proliferation, and this effect is independent of conventional ROCK pathway but involves inactivation of AKT pathway.

Accumulating evidences suggest that peripheral nerve injury (PNI) may initiate astrocytic responses in the central nervous system (CNS). However, the response of astrocytes in the spinal ventral horn and its potential role in nerve regeneration after PNI remain unclear. Herein, we firstly illustrated that astrocytes in the spinal ventral horn were dramatically activated in the early stage following sciatic nerve injury, and these profiles were eliminated in the chronic stage. Additionally, we found that the expression of neurotrophins, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3), also accompanied with astrocyte activation. In comparison with the irreversible transected subjects, astrocyte activation and the neurotrophic upregulation in the early stage were more drastic in case the transected nerve was rebridged immediately after injury. Furthermore, administering fluorocitrate to inhibit astrocyte activation resulted in decreased neurotrophin expression in the spinal ventral horn and delayed axonal regeneration in the nerve as well as motor function recovery. Overall, the present study indicates that peripheral nerve injury can initiate astrocyte activation accompanied with neurotrophin upregulation in the spinal ventral horn. The above responses mainly occur in the early stage of PNI and may contribute to nerve regeneration and motor function recovery.

Compared to tissue sectioning techniques, the technique of teasing single nerve fibers provides a better way to understand the structures of myelin sheaths and axons of the peripheral myelinated nerves. This protocol describes a method for preparation of teased single nerve fibers from rat sciatic nerve. In this protocol, fixed nerves are teased into single individual fibers and arranged onto adhesion microscope slides for further immuno-staining.

Primary cultured Schwann cells (SCs) are widely used in the investigation of the biology of SC and are important seed cells for neural tissue engineering. Here, we describe a novel protocol for harvesting primary cultured SCs from neonatal Sprague-Dawley (SD) rats. In the present protocol, dissociated SCs are isolated from the spinal nerves of neonatal rats and purified by the treatment of cytosine arabinoside (AraC).

This study aimed to analyze the correlation between the phenotype and genotype of Chinese patients with early-onset lamin A (LMNA)-related muscular dystrophy (MD). The clinical and myopathological data of 21 Chinese pediatric patients with early-onset LMNA-related MD were collected and analyzed. LMNA gene mutation analysis was performed by direct sequencing of genomic DNA. Sublocalization of wild-type and mutant proteins were observed by immunofluorescence using cultured fibroblasts and human embryonic kidney 293 (HEK 293) cell. Seven patients were diagnosed with Emery-Dreifuss muscular dystrophy (EDMD) and 14 were diagnosed with LMNA-associated congenital muscular dystrophy (L-CMD). Four biopsy specimens from the L-CMD cases exhibited inflammatory changes. Abnormal nuclear morphology was observed with both transmission electron microscopy and lamin A/C staining. We identified 10 novel and nine known LMNA gene mutations in the 21 patients. Some mutations (c.91G>A, c.94_96delAAG, c.116A>G, c.745C>T, c.746G>A, and c.1580G>C) were well correlated with EDMD or L-CMD. LMNA-related MD has a common symptom triad of muscle weakness, joint contractures, and cardiac involvement, but the severity of symptoms and disease progression differ greatly. Inflammatory change in biopsied muscle is a characteristic of early-stage L-CMD. Phenotype-genotype analysis determines that some mutations are well correlated with LMNA-related MD.

Abstract Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by hyperglycemia and insulin resistance. Mung bean sprouts are traditionally considered a “folk” hypoglycemic food and their pharmacological effects and underlying mechanisms warrant further investigation. Purpose This study aimed to investigate the anti-diabetic effects of the exosomes-like nanoparticles in mung bean sprouts (MELNs) and explore the related molecular mechanisms. Results MELNs were isolated using a differential centrifugation-polyethylene glycol (PEG) method, and the identification of MELNs were confirmed by PAGE gel electrophoresis, agarose gel electrophoresis, thin-layer chromatography (TLC), and transmission electron microscopy (TEM). In the high-fat diet/streptozotocin (HFD/STZ) mouse model, MELNs ameliorated the progression of T2DM by increasing oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) results, decreasing the fasting blood glucose level, and reducing the serum triglycerides (TG) and total cholesterol (TC). Histopathological examinations indicated MELNs diminished inflammatory infiltration of hepatocytes and amplified the area of islet B cells. In addition, MELNs decreased the oxidative stress levels in liver tissue and had good biocompatibility. In vitro experiments verified that MELNs improved the viability of glucosamine (GlcN) induced insulin-resistant hepatocytes. Furthermore, this study also revealed that MELNs upregulated GLUT4 & Nrf2 and down-regulated GSK-3β via activating the PI3K/Akt signaling pathway, promoting the production of antioxidant enzymes, such as HO-1 and SOD, to reduce oxidative stress. Conclusion MELNs mitigated the progression of type 2 diabetes in HFD/STZ mouse model. The underlying molecular mechanism is related to PI3K/Akt/GLUT4/GSK-3β signaling pathway.

Background LMNA-related muscular dystrophy is caused by mutations in LMNA gene. We aimed to identify genetic variations and clinical features in a large cohort of Chinese patients with LMNA mutations in an attempt to establish genotype-phenotype correlation. Methods The clinical presentations of patients with LMNA-related muscular dystrophy were recorded using retrospective and prospective cohort study. LMNA mutation analysis was performed by Sanger sequencing or next-generation sequencing. Mosaicism was detected by personal genome machine amplicon deep sequencing for mosaicism. Results Eighty-four patients were identified to harbour LMNA mutations. Forty-one of those were diagnosed with LMNA-related congenital muscular dystrophy (L-CMD), 32 with Emery-Dreifuss muscular dystrophy (EDMD) and 11 with limb-girdle muscular dystrophy type 1B (LGMD1B). We identified 21 novel and 29 known LMNA mutations. Two frequent mutations were identified: c.745C>T and c.1357C>T. A correlation between the location of mutation and the clinical phenotype was observed: mutations affecting the head and coil 2A domains mainly occurred in L-CMD, while the coil 2B and Ig-like domains mainly related to EDMD and LGMD1B. We found somatic mosaicism in one parent of four probands. Muscle biopsies revealed 11 of 20 biopsied L-CMD exhibited inflammatory changes, and muscle cell ultrastructure showed abnormal nuclear morphology. Conclusions Our detailed clinical and genetic analysis of 84 patients with LMNA-related muscular dystrophy expands clinical spectrum and broadens genetic variations caused by LMNA mutations. We identified 21 novel and 29 known LMNA mutations and found two frequent mutations. A correlation between the location of mutation and the clinical severity was observed. Preliminary data suggested that low-dose corticosteroid treatment may be effective. [ABSTRACT FROM AUTHOR]

A real-time push software for environmental meteorological monitoring data based on big data was designed to improve the real-time and accuracy of data push. The data source module in the real-time push software for environmental meteorological monitoring data based on big data is responsible for storing environmental meteorological monitoring data. The integration module is responsible for extracting the required data. The big data module is responsible for preprocessing the extracted data, using RBF artificial neural network algorithm to build a meteorological prediction model for it, and obtaining the prediction results. Module, intelligent information push through regression restricted boltzmann machine recommendation algorithm, to extract the predicted results of interest to the user in the environmental meteorological monitoring data, restricted boltzmann machine recommendation algorithm based on regression is introduced in collaborative filtering algorithm restricted boltzmann machine, formed based on the user and the project of restricted boltzmann machine collaborative filtering algorithm, by using linear model integration of recommended results, through intelligent notification module will recommend the push to the intelligent terminal, to achieve environmental meteorological monitoring data real-time push. The experiment proves that the software can effectively push the environmental meteorological monitoring data to users in real time, with fast speed and high accuracy. [ABSTRACT FROM AUTHOR]

Although pruning contributes to the growth and development of new shoots, it is important to note that the growth potential and yield of tea varieties may differ after pruning due to genetic and environmental factors. In this experiment, 20 different varieties of tea plants were used to observe their potential for growth, shoot development, and other phenotypic indexes after pruning. The study aimed to determine the suitability of each variety for heavy pruning. It was concluded that there were obvious differences in tree strength and new growth after pruning of the different varieties, with ‘Zhongcha 302’ exhibiting the strongest growth and ‘Emei Wenchun’ showing the weakest growth. In order to understand the molecular mechanisms involved, a transcriptomic analysis was carried out on the two tea varieties. The results of the data indicate that the expression of CYP450 family was high in ‘Zhongcha 302’. In ‘Emei Wenchun’, the expression of NCED was higher than that in ‘Zhongcha 302’. The KEGG results indicate that pruning stimulates the expression of genes involved in phytohormone signalling and plant–pathogen interaction pathways in tea plants. The study offered scientific guidance for tea plant pruning suitability and preliminarily revealed the regulatory mechanism of new shoot growth in different tea plant varieties at the transcriptome level.

Nuclear factor Y (NF-Y) is a class of transcription factors consisting of NF-YA, NF-YB and NF-YC subunits, which are widely distributed in eukaryotes. The NF-YC subunit regulates plant growth and development and plays an important role in the response to stresses. However, there are few reports on this gene subfamily in tea plants. In this study, nine CsNF-YC genes were identified in the genome of ‘Longjing 43’. Their phylogeny, gene structure, promoter cis-acting elements, motifs and chromosomal localization of these gene were analyzed. Tissue expression characterization revealed that most of the CsNF-YCs were expressed at low levels in the terminal buds and at relatively high levels in the flowers and roots. CsNF-YC genes responded significantly to gibberellic acid (GA) and abscisic acid (ABA) treatments. We further focused on CsNF-YC6 because it may be involved in the growth and development of tea plants and the regulation of response to abiotic stresses. The CsNF-YC6 protein is localized in the nucleus. Arabidopsis that overexpressed CsNF-YC6 (CsNF-YC6-OE) showed increased seed germination and increased root length under ABA and GA treatments. In addition, the number of cauline leaves, stem lengths and silique numbers were significantly higher in overexpressing Arabidopsis lines than wild type under long-day growth conditions, and CsNF-YC6 promoted primary root growth and increased flowering in Arabidopsis. qPCR analysis showed that in CsNF-YC6-OE lines, flowering pathway-related genes were transcribed at higher levels than wild type. The investigation of the CsNF-YC gene has unveiled that CsNF-YC6 plays a pivotal role in plant growth, root and flower development, as well as responses to abiotic stress.

Nitrogen (N) and selenium (Se) are beneficial for tea growth and tea quality; however, it is unknown how the combined application of N and Se affects tea quality and N uptake and utilization in tea plants. In the present study, a hydroponic experiment with three N levels (0, 2 and 4.5 mmol/L) and three Se levels (0, 0.3 and 3 mg/L) was carried out with ‘Chuancha No.2’ as the material, and the contents of tea polyphenols, amino acids and caffeine as well as the expression levels of genes related to N uptake and utilization in tea plants were tracked. The findings reveal that the contents of tea polyphenols, AAs and caffeine in new shoots were the highest when supplied with 0.3 mg/L Se and 4.5 mmol/L N, while the contents of total N, AAs and tea polyphenols in mature leaves were the highest at the concentrations of 3 mg/L Se and 2 mmol/L N. Se supply (0.3 and 3 mg/L) induced an increase in amino acid and tea polyphenol contents in tea shoots under N deficiency conditions, whereas total N content, tea polyphenols and AAs in mature leaves and total N content in tea roots decreased significantly. When supplied with N (2 mmol/L and 4.5 mmol/L), the contents of tea polyphenols and caffeine in new shoots first increased and then decreased with the increase in Se concentration, while the total N content in mature leaves and roots increased. In leaves, CsAMT1.1, CsAMT1.2 and CsAMT3.1 had similar trends, and their expression levels were remarkably upregulated when supplied with 0.3 mg/L Se or 2 mmol/L N, respectively; the expression level of CsGS1.1 was significantly induced by N and Se, while CsGS1.2 and CsTS1 were mainly induced by N. In roots, CsAMT1.1 could play a major role in N uptake under the combined application of N and Se; CsGS1.2 expression was significantly induced compared to CsGS1.1 under the combined application of N and Se. This study explored the potential of the interaction of Se and N to promote tea quality and N uptake and utilization in tea plants.

(1) Background: Anthocyanins, the main pigments in plants, are influenced by both temperature and photoperiod. However, the specific mechanisms underlying anthocyanin accumulation in tea plants in response to these two environmental factors remain unclear. (2) Methods: This study subjected potted ‘Ziyan’ tea plants to four types of day-length and temperature treatments (HL (28 °C, 16 h), HS (28 °C, 8 h), LL (18 °C, 16 h), and LS (18 °C, 8 h)), and then conducted targeted metabolomic and transcriptomic analyses of the samples. (3) Results: Long photoperiods and low temperatures both promoted anthocyanin accumulation in the new shoots of the tea plants. Furthermore, the enhancing effects of these two environmental factors on anthocyanin accumulation are additive and exhibit interactive effects. Through a combined analysis of metabolomics and transcriptomics, five key differentially accumulated metabolites (DAMs) and twenty-two key differentially expressed genes (DEGs) were identified, the latter being found to participate in the regulation of anthocyanin biosynthesis pathways under varying light and temperature conditions. In summary, extended photoperiods primarily increase the content levels of ten metabolites, including cyanidin and naringenin-7-O-glucoside, by upregulating CHS, F3H, and ANS genes. In contrast, low temperatures primarily enhance the synthesis of seven anthocyanins, including cyanidin and cyanidin-3-O-rutinoside, by upregulating the ANS and UFGT genes. (4) Conclusions: Collectively, the differences in the expression levels of CHS, F3H, ANS, and UFGT might be responsible for ‘Ziyan’ tea plants’ purple shoot coloration, providing important data towards the discovery of candidate genes and molecular bases controlling the purple leaves of these tea plants under varied photoperiods and temperatures.

Cancer, a common malignant disease, is one of the predominant causes of diseases that lead to death. Additionally, cancer is often detected in advanced stages and cannot be radically cured. Consequently, there is an urgent need for reliable and easily detectable markers to identify and monitor cancer onset and progression as early as possible. Our aim was to systematically review the relevant roles of cathepsin K (CTSK) in various possible cancers in existing studies. CTSK, a well-known key enzyme in the bone resorption process and most studied for its roles in the effective degradation of the bone extracellular matrix, is expressed in various organs. Nowadays, CTSK has been involved in various cancers such as prostate cancer, breast cancer, bone cancer, renal carcinoma, lung cancer and other cancers. In addition, CTSK can promote tumor cells proliferation, invasion and migration, and its mechanism may be related to RANK/RANKL, TGF-β, mTOR and the Wnt/β-catenin signaling pathway. Clinically, some progress has been made with the use of cathepsin K inhibitors in the treatment of certain cancers. This paper reviewed our current understanding of the possible roles of CTSK in various cancers and discussed its potential as a biomarker and/or novel molecular target for various cancers.