TIP aquaporins in Cyperus esculentus: genome-wide identification, expression profiles, subcellular localizations, and interaction patterns.

BACKGROUND: Tonoplast intrinsic proteins (TIPs), which typically mediate water transport across vacuolar membranes, play an essential role in plant growth, development, and stress responses. However, their characterization in tigernut (Cyperus esculentus L.), an oil-bearing tuber plant of the Cyperaceae family, is still in the infancy. RESULTS: In this study, a first genome-wide characterization of the TIP subfamily was conducted in tigernut, resulting in ten members representing five previously defined phylogenetic groups, i.e., TIP1-5. Although the gene amounts are equal to that present in two model plants Arabidopsis and rice, the group composition and/or evolution pattern were shown to be different. Except for CeTIP1;3 that has no counterpart in both Arabidopsis and rice, complex orthologous relationships of 1:1, 1:2, 1:3, 2:1, and 2:2 were observed. Expansion of the CeTIP subfamily was contributed by whole-genome duplication (WGD), transposed, and dispersed duplications. In contrast to the recent WGD-derivation of CeTIP3;1/-3;2, synteny analyses indicated that TIP4 and - 5 are old WGD repeats of TIP2, appearing sometime before monocot-eudicot divergence. Expression analysis revealed that CeTIP genes exhibit diverse expression profiles and are subjected to developmental and diurnal fluctuation regulation. Moreover, when transiently overexpressed in tobacco leaves, CeTIP1;1 was shown to locate in the vacuolar membrane and function in homo/heteromultimer, whereas CeTIP2;1 is located in the cell membrane and only function in heteromultimer. Interestingly, CeTIP1;1 could mediate the tonoplast-localization of CeTIP2;1 via protein interaction, implying complex regulatory patterns. CONCLUSIONS: Our findings provide a global view of CeTIP genes, which provide valuable information for further functional analysis and genetic improvement through manipulating key members in tigernut.

Acyl carrier protein tag can enhance tobacco etch virus protease stability and promote its covalent immobilisation.

Fusion expression is widely employed to enhance the solubility of recombinant proteins. However, removal of the fusion tag is often required due to its potential impact on the structure and activity of passenger proteins. Tobacco etch virus (TEV) protease is widely used for this purpose due to its stringent sequence recognition. In the present work, fusion to the acyl carrier protein from E. coli fatty acid synthase (ACP) significantly increased the yield of recombinant soluble TEV, and the ACP tag also greatly improved TEV stability. The cleavage activity of TEV was not affected by the ACP fusion tag, and ACP-TEV retained high activity, even at unfavourable pH values. Moreover, ACP-TEV could be efficiently modified by co-expressed E. coli holo-ACP synthase (AcpS), leading to covalent attachment of 4'-phosphopantetheine (4'-PP) group to ACP. The sulfhydryl group of the long, flexible 4'-PP chain displayed high specific reactivity with iodoacetyl groups on the solid support. Thus, TEV could be immobilised effectively and conveniently via the active holo-ACP, and immobilised TEV retained high cleavage activity after a long storage period and several cycles of reuse. As a low-cost and recyclable biocatalyst, TEV immobilised by this method holds promise for biotechnological research and development. KEY POINTS: • The ACP tag greatly increased the soluble expression and stability of TEV protease. • The ACP tag did not affect the cleavage activity of TEV. • The holo-ACP Tag effectively mediated the covalent immobilisation of TEV.

Molecular characterization of oleosin genes in Cyperus esculentus, a Cyperaceae plant producing oil in underground tubers.

KEY MESSAGE: CeOLE genes exhibit a tuber-predominant expression pattern and their mRNA/protein abundances are positively correlated with oil accumulation during tuber development. Overexpression could significantly increase the oil content of tobacco leaves. Oleosins (OLEs) are abundant structural proteins of lipid droplets (LDs) that function in LD formation and stabilization in seeds of oil crops. However, little information is available on their roles in vegetative tissues. In this study, we present the first genome-wide characterization of the oleosin family in tigernut (Cyperus esculentus L., Cyperaceae), a rare example accumulating high amounts of oil in underground tubers. Six members identified represent three previously defined clades (i.e. U, SL and SH) or six out of seven orthogroups (i.e. U, SL1, SL2, and SH1-3) proposed in this study. Comparative genomics analysis reveals that lineage-specific expansion of Clades SL and SH was contributed by whole-genome duplication and dispersed duplication, respectively. Moreover, presence of SL2 and SH3 in Juncus effuses implies their appearance sometime before Cyperaceae-Juncaceae divergence, whereas SH2 appears to be Cyperaceae specific. Expression analysis showed that CeOLE genes exhibit a tuber-predominant expression pattern and transcript levels are considerably more abundant than homologs in the close relative Cyperus rotundus. Moreover, CeOLE mRNA and protein abundances were shown to positively correlate with oil accumulation during tuber development. Additionally, two dominant isoforms (i.e. CeOLE2 and -5) were shown to locate in LDs as well as the endoplasmic reticulum of tobacco (Nicotiana benthamiana) leaves, and are more likely to function in homo and heteromultimers. Furthermore, overexpression of CeOLE2 and -5 in tobacco leaves could significantly increase the oil content, supporting their roles in oil accumulation. These findings provide insights into lineage-specific family evolution and putative roles of CeOLE genes in oil accumulation of vegetative tissues, which facilitate further genetic improvement for tigernut.

Application of OCT-Derived Attenuation Coefficient in Acute Burn-Damaged Skin.

BACKGROUND AND OBJECTIVES: There remains a need to objectively monitor burn wound healing within a clinical setting, and optical coherence tomography (OCT) is proving itself one of the ideal modalities for just such a use. The aim of this study is to utilize the noninvasive and multipurpose capabilities of OCT, along with its cellular-level resolution, to demonstrate the application of optical attenuation coefficient (OAC), as derived from OCT data, to facilitate the automatic digital segmentation of the epidermis from scan images and to work as an objective indicator for burn wound healing assessment. STUDY DESIGN/MATERIALS AND METHODS: A simple, yet efficient, method was used to estimate OAC from OCT images taken over multiple time points following acute burn injury. This method enhanced dermal-epidermal junction (DEJ) contrast, which facilitated the automatic segmentation of the epidermis for subsequent thickness measurements. In addition, we also measured and compared the average OAC of the dermis within said burns for correlative purposes. RESULTS: Compared with unaltered OCT maps, enhanced DEJ contrast was shown in OAC maps, both from single A-lines and completed B-frames. En face epidermal thickness and dermal OAC maps both demonstrated significant changes between imaging sessions following burn injury, such as a loss of epidermal texture and decreased OAC. Quantitative analysis also showed that OAC of acute burned skin decreased below that of healthy skin following injury. CONCLUSIONS: Our study has demonstrated that the OAC estimated from OCT data can be used to enhance imaging contrast to facilitate the automatic segmentation of the epidermal layer, as well as help elucidate our understanding of the pathological changes that occur in human skin when exposed to acute burn injury, which could serve as an objective indicator of skin injury and healing.

Hanshiyi Formula, a medicine for Sars-CoV2 infection in China, reduced the proportion of mild and moderate COVID-19 patients turning to severe status: A cohort study.

We formulated a traditional Chinese medicine (TCM) prescription, Hanshiyi Formula (HSYF), which was approved and promoted by the Wuhan Municipal Health Commission for treating mild and moderate coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of HSYF on the progression to severe disease in mild and moderate COVID-19 patients. We conducted a retrospective cohort study of patients with mild and moderate COVID-19 in a quarantine station in Wuchang District, Wuhan. Using the real-time Internet information collection application and Centers for Disease Control for the Wuchang District, patient data were collected through patient self-reports and follow-ups. HSYF intervention was defined as the exposure. The primary outcome was the proportion of patients who progressed to a severe disease status, and a stratification analysis was performed. Univariate and multivariate regression analyses were performed to identify influencing factors that may affect the outcome. Further, we used propensity score matching (PSM) to assess the effect of HSYF intervention on the conversion of mild and moderate to a severe disease status. Totally, 721 mild and moderate COVID-19 patients were enrolled, including 430 HSYF users (exposed group) and 291 non-users (control group). No cases in the exposed group and 19 (6.5 %, P < 0.001) cases in the control group progressed to severe disease, and the difference between the two groups (exposed group-control group) was -6.5 % [95 % confidence interval (CI): (-8.87 %, -4.13 %)]. Univariate regression analysis revealed sex (male), age, fever, cough, and fatigue as risk factors for progression to severe disease. After PSM, none of the HSYF users and 7 (4.7 %, P = 0.022) non-users transitioned to severe disease, and the difference between the two groups (exposed group-control group) was -4.7 % [95 % CI: (-8.2 %, -1.2 %)]. Multivariate regression analysis revealed that sex (male) [OR: 3.145; 95 % CI: 1.036-9.545; P = 0.043] and age (> 48 years) [odds ratio (OR): 1.044; 95 % CI: 1.001-1.088; P = 0.044] were independent risk factors for conversion to severe disease. Therefore, HSYF can significantly reduce the progression to severe disease in patients with mild and moderate COVID-19, which may effectively prevent and treat the disease. However, further larger clinical studies are required to verify our results.

Efficacy of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in treatment of COVID-19: A randomized controlled trial.

BACKGROUND: With the global epidemic of coronavirus disease (COVID-19), China has made progress in the prevention and control of the epidemic, and traditional Chinese medicine (TCM) has played a key role in dealing with the disease's effects on the respiratory system. This randomized controlled clinical trial evaluated the clinical efficacy and prognosis of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in patients with COVID-19. METHODS: A total of 283 patients participated in this clinical trial, and participants were randomly assigned to receive either 1) Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules or 2) Linahua granules, both combined with western medicine, or 3) western medicine alone for 14 days. At the end of the trial, the improvement and resolution rates of clinical symptoms and the rate of patients who progressed to severe disease status were evaluated. RESULTS: After 14 days of treatment, there was no significant difference in the improvement rate of clinical symptoms among the three groups (P > 0.05). Huoxiang Zhengqi dropping pills combined with Lianhua Qingwen granules has advantages in the treatment of nausea, vomiting and limb soreness. During treatment, all participants were treated with western medicine, and there was a significant difference in the use of macrolides among the three groups (P < 0.05). Specifically, the utilization rate of antibiotics in the western medicine group was significantly greater than that of the other two groups. Among the 182 diagnosed patients who completed this clinical trial, 13 patients progressed to severe disease, including one case in the Huoxiang + Lianhua group (1.6 %), five cases in the Lianhua group (8.6 %), and seven cases in the western medicine group (11.1 %). There was no statistical differences in this rate among the three groups (P > 0.05). However, the proportion of patients who progressed to severe disease in the Huoxiang + Lianhua group was the lowest, suggesting that the combination of TCM with western medicine has a potential advantage in improving the prognosis of patients with COVID-19. CONCLUSION: The use of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules combined with western medicine may have clinical advantages for COVID-19 patients in improving clinical symptoms, reducing utilization rate of anti-infective drugs, and improving patient prognosis, which could pave the way for the use of complementary medicine in treating this infection.

Different intervention strategies for preventing type 2 diabetes mellitus in China: A systematic review and network meta-analysis of randomized controlled trials.

Different strategies are increasingly used for early intervention in prediabetes in China, but the effects of these strategies on incident diabetes have not yet been confirmed. The aim of the present study was to assess systematically the effects of different strategies for preventing diabetes, aimed at Chinese people with prediabetes. Seven electronic databases were searched to identify eligible trials published from inception to September 20, 2016. Randomized controlled trials with a minimum follow-up duration of 6 months were included. Standard pairwise meta-analysis with a random-effects model and network meta-analysis with a frequentist framework were performed. A total of 63 studies, including 11 intervention strategies, were included. Compared with placebo, all strategies, except for lipid-affecting drugs and sitagliptin, reduced the rate of incident diabetes with different levels of effectiveness, ranging from 0.18 (95% confidence interval [CI] 0.12, 0.27) to 0.39 (95% CI 0.20, 0.75). Ranking probability analysis indicated that metformin and ß-cell-stimulating drugs reduced the risk of diabetes most, with probabilities of 87.4% and 81%, respectively. Ethnicity and cultural factors should be considered for diabetes prevention. Most of the included trials were of poor methodological quality, however, and the results should be interpreted with caution.

The research trends of ferroptosis in diabetes: a bibliometric analysis.

Objective: Exploring the mechanism of ferroptosis as a potential avenue for investigating the pathogenesis and therapeutic outlook of diabetes mellitus and its complications has emerged as a focal point within recent years. Herein, we employ a bibliometric approach to delineate the current landscape of ferroptosis research in the context of diabetes mellitus. Our objective is to furnish insights and scholarly references conducive to the advancement of comprehensive investigations and innovations in related domains. Methods: We included studies on ferroptosis in diabetes, obtained from the Web of Science Core Collection. All publications were transported in plaintext full-record format and were analyzed by CiteSpace 6.2.R4 for bibliometric analysis. Results: Four hundred and forty-eight records that met the criteria were included. The publications released during the initial 3 years were relatively small, while there was a sudden surge of publications published in 2022 and 2023. Representing 41 countries and 173 institutions, China and Wuhan University led the research on ferroptosis in diabetes. The author with the highest number of published papers is Zhongming Wu, while Dixon SJ is the most frequently cited author. The journal with the highest number of co-citations is Cell. The most common keywords include oxidative stress, cell death, lipid peroxidation, and metabolism. Extracted keywords predominantly focus on NLRP3 inflammatory, diabetic kidney disease, mitochondria, iron overload, and cardiomyopathy. Conclusion: The escalating recognition of ferroptosis as a potential therapeutic target for deciphering the intricate mechanisms underlying diabetes and its complications is underscored by a noteworthy surge in relevant research publications. This surge has catapulted ferroptosis into the spotlight as a burgeoning and vibrant research focus within the field.

Deciphering the shared mechanisms of Gegen Qinlian Decoction in treating type 2 diabetes and ulcerative colitis via bioinformatics and machine learning.

Background: Although previous clinical studies and animal experiments have demonstrated the efficacy of Gegen Qinlian Decoction (GQD) in treating Type 2 Diabetes Mellitus (T2DM) and Ulcerative Colitis (UC), the underlying mechanisms of its therapeutic effects remain elusive. Purpose: This study aims to investigate the shared pathogenic mechanisms between T2DM and UC and elucidate the mechanisms through which GQD modulates these diseases using bioinformatics approaches. Methods: Data for this study were sourced from the Gene Expression Omnibus (GEO) database. Targets of GQD were identified using PharmMapper and SwissTargetPrediction, while targets associated with T2DM and UC were compiled from the DrugBank, GeneCards, Therapeutic Target Database (TTD), DisGeNET databases, and differentially expressed genes (DEGs). Our analysis encompassed six approaches: weighted gene co-expression network analysis (WGCNA), immune infiltration analysis, single-cell sequencing analysis, machine learning, DEG analysis, and network pharmacology. Results: Through GO and KEGG analysis of weighted gene co-expression network analysis (WGCNA) modular genes and DEGs intersection, we found that the co-morbidity between T2DM and UC is primarily associated with immune-inflammatory pathways, including IL-17, TNF, chemokine, and toll-like receptor signaling pathways. Immune infiltration analysis supported these findings. Three distinct machine learning studies identified IGFBP3 as a biomarker for GQD in treating T2DM, while BACE2, EPHB4, and EPHA2 emerged as biomarkers for GQD in UC treatment. Network pharmacology revealed that GQD treatment for T2DM and UC mainly targets immune-inflammatory pathways like Toll-like receptor, IL-17, TNF, MAPK, and PI3K-Akt signaling pathways. Conclusion: This study provides insights into the shared pathogenesis of T2DM and UC and clarifies the regulatory mechanisms of GQD on these conditions. It also proposes novel targets and therapeutic strategies for individuals suffering from T2DM and UC.

Exploring the molecular mechanism of Xuebifang in the treatment of diabetic peripheral neuropathy based on bioinformatics and network pharmacology.

Background: Xuebifang (XBF), a potent Chinese herbal formula, has been employed in managing diabetic peripheral neuropathy (DPN). Nevertheless, the precise mechanism of its action remains enigmatic. Purpose: The primary objective of this investigation is to employ a bioinformatics-driven approach combined with network pharmacology to comprehensively explore the therapeutic mechanism of XBF in the context of DPN. Study design and Methods: The active chemicals and their respective targets of XBF were sourced from the TCMSP and BATMAN databases. Differentially expressed genes (DEGs) related to DPN were obtained from the GEO database. The targets associated with DPN were compiled from the OMIM, GeneCards, and DrugBank databases. The analysis of GO, KEGG pathway enrichment, as well as immuno-infiltration analysis, was conducted using the R language. The investigation focused on the distribution of therapeutic targets of XBF within human organs or cells. Subsequently, molecular docking was employed to evaluate the interactions between potential targets and active compounds of XBF concerning the treatment of DPN. Results: The study successfully identified a total of 122 active compounds and 272 targets associated with XBF. 5 core targets of XBF for DPN were discovered by building PPI network. According to GO and KEGG pathway enrichment analysis, the mechanisms of XBF for DPN could be related to inflammation, immune regulation, and pivotal signalling pathways such as the TNF, TLR, CLR, and NOD-like receptor signalling pathways. These findings were further supported by immune infiltration analysis and localization of immune organs and cells. Moreover, the molecular docking simulations demonstrated a strong binding affinity between the active chemicals and the carefully selected targets. Conclusion: In summary, this study proposes a novel treatment model for XBF in DPN, and it also offers a new perspective for exploring the principles of traditional Chinese medicine (TCM) in the clinical management of DPN.

Analysis of Carica papaya Informs Lineage-Specific Evolution of the Aquaporin (AQP) Family in Brassicales.

Aquaporins (AQPs), a type of intrinsic membrane proteins that transport water and small solutes across biological membranes, play crucial roles in plant growth and development. This study presents a first genome-wide identification and comparative analysis of the AQP gene family in papaya (Carica papaya L.), an economically and nutritionally important fruit tree of tropical and subtropical regions. A total of 29 CpAQP genes were identified, which represent five subfamilies, i.e., nine plasma intrinsic membrane proteins (PIPs), eight tonoplast intrinsic proteins (TIPs), seven NOD26-like intrinsic proteins (NIPs), two X intrinsic proteins (XIPs), and three small basic intrinsic proteins (SIPs). Although the family is smaller than the 35 members reported in Arabidopsis, it is highly diverse, and the presence of CpXIP genes as well as orthologs in Moringa oleifera and Bretschneidera sinensis implies that the complete loss of the XIP subfamily in Arabidopsis is lineage-specific, sometime after its split with papaya but before Brassicaceae-Cleomaceae divergence. Reciprocal best hit-based sequence comparison of 530 AQPs and synteny analyses revealed that CpAQP genes belong to 29 out of 61 identified orthogroups, and lineage-specific evolution was frequently observed in Brassicales. Significantly, the well-characterized NIP3 group was completely lost; lineage-specific loss of the NIP8 group in Brassicaceae occurred sometime before the divergence with Cleomaceae, and lineage-specific loss of NIP2 and SIP3 groups in Brassicaceae occurred sometime after the split with Cleomaceae. In contrast to a predominant role of recent whole-genome duplications (WGDs) on the family expansion in B. sinensis, Tarenaya hassleriana, and Brassicaceae plants, no recent AQP repeats were identified in papaya, and ancient WGD repeats are mainly confined to the PIP subfamily. Subfamily even group-specific evolution was uncovered via comparing exon-intron structures, conserved motifs, the aromatic/arginine selectivity filter, and gene expression profiles. Moreover, down-regulation during fruit ripening and expression divergence of duplicated CpAQP genes were frequently observed in papaya. These findings will not only improve our knowledge on lineage-specific family evolution in Brassicales, but also provide valuable information for further studies of AQP genes in papaya and species beyond.

A literature review on Epimedium, a medicinal plant with promising slow aging properties.

Ethnopharmacological relevance: Aging is related to many factors, such as genes, oxidative damage, metabolic abnormalities, immune regulation and sex hormones. This article reviews the pharmacological mechanism of Epimedium on slow aging from six aspects: gene regulation, antioxidant, the regulation of metabolism, the modulation of the immune system, the regulation of sex hormone, and clinical efficacy.Aim of the studyThrough literature review, to discover the potential pharmacological mechanism of Epimedium for slow aging. Materials and methods: We reviewed the literature on the applications of Epimedium in multiple systems and the potential underlying mechanisms with systematic and comprehensive illustrations. The review includes the following aspects: gene regulation, antioxidant, the regulation of metabolism, the modulation of the immune system, the regulation of sex hormone, clinical efficacy and safety. Results: The slow aging active components of Epimedium may be flavonoids, such as Epimedins A, B, C and icariin The slow aging effect of Epimedium may be related to gene regulation, antioxidant, the regulation of metabolism, the modulation of the immune system, and the regulation of sex hormone. No severe adverse reaction has been reported. Conclusions: Epimedium has potential slow aging effect and been widely used in the clinic for aging-related diseases in the real world in China; however, large-scale studies are still needed.

Semi-Automated Analysis of Foveal Maturity in Premature and Full-Term Infants Using Handheld Swept-Source Optical Coherence Tomography.

Purpose: To develop a semi-automated method of measuring foveal maturity using investigational handheld swept source-optical coherence tomography (SS-OCT). Methods: In this prospective, observational study, full-term newborns and preterm infants undergoing routine retinopathy of prematurity screening were imaged. Semi-automated analysis measured foveal angle and chorioretinal thicknesses at the central fovea and average two-sided parafovea by three-grader consensus, correlating with OCT features and demographics. Results: One hundred ninety-four imaging sessions from 70 infants were included (47.8% girls, 37.6 ± 3.4 weeks postmenstrual age, 26 preterm infants with birth weight 1057 ± 325.0, gestational age 29.0 ± 3.0 weeks). Foveal angle (96.1 ± 22.0 degrees) steepened with increasing birth weight (P = 0.003), decreasing inner retinal layer thickness, and increasing gestational age, postmenstrual age, and foveal and parafoveal choroidal thickness (all P < 0.001). Inner retinal fovea/parafovea ratio (0.4 ± 0.2) correlated with increasing inner foveal layers, decreasing postmenstrual age, gestational age, and birth weight (all P < 0.001). Outer retinal F/P ratio (0.7 ± 0.2) correlated with ellipsoid zone presence (P < 0.001), increased gestational age (P = 0.002), and birth weight (P = 0.003). Foveal (447.8 ± 120.6 microns) and parafoveal (420.9 ± 109.2) choroidal thicknesses correlated with foveal ellipsoid zone presence (P = 0.007 and P = 0.01, respectively), postmenstrual age, birth weight, gestational age, and decreasing inner retinal layers (all P < 0.001). Conclusions: Foveal development is dynamic and partially observed through semi-automated analysis of handheld SS-OCT imaging. Translational Relevance: Semi-automated analysis of SS-OCT images can identify measures of foveal maturity.

Practice and principle of traditional Chinese medicine for the prevention and treatment of COVID-19.

Traditional Chinese medicine (TCM) has played an important role in the prevention and treatment of Coronavirus disease 2019 (COVID-19) epidemic in China. The integration of Chinese and Western medicine is an important feature of Chinese COVID-19 prevention and treatment. According to a series of evidence-based studies, TCM can reduce the infection rate of severe acute respiratory syndrome coronavirus 2 in high-risk groups. For patients with mild and moderate forms of COVID-19, TCM can relieve the related signs and symptoms, shorten the period of nucleic-acid negative conversion, and reduce conversion rate to the severe form of the disease. For COVID-19 patients with severe and critical illnesses, TCM can improve inflammatory indicators and blood oxygen saturation, shorten the hospital stay, and reduce the mortality rate. During recovery, TCM can improve patients' symptoms, promote organ function recovery, boost the quality of patients' life, and reduce the nucleic-acid repositive conversion rate. A series of mechanism research studies revealed that capability of TCM to treat COVID-19 through antiviral and anti-inflammatory effects, immune regulation, and protection of organ function via a multicomponent, multitarget, and multipathway approach.

Genomic Analysis of LEA Genes in Carica papaya and Insight into Lineage-Specific Family Evolution in Brassicales.

Late embryogenesis abundant (LEA) proteins comprise a diverse superfamily involved in plant development and stress responses. This study presents a first genome-wide analysis of LEA genes in papaya (Carica papaya L., Caricaceae), an economically important tree fruit crop widely cultivated in the tropics and subtropics. A total of 28 members were identified from the papaya genome, which belong to eight families with defined Pfam domains, i.e., LEA_1 (3), LEA_2 (4), LEA_3 (5), LEA_4 (5), LEA_5 (2), LEA_6 (2), DHN (4), and SMP (3). The family numbers are comparable to those present in Ricinus communis (Euphorbiaceae, 28) and Moringa oleifera (Moringaceae, 29), but relatively less than that found in Moringa oleifera (Cleomaceae, 39) and Arabidopsis thaliana (Brassicaceae, 51), implying lineage-specific evolution in Brassicales. Indeed, best-reciprocal-hit-based sequence comparison and synteny analysis revealed the presence of 29 orthogroups, and significant gene expansion in Tarenaya and Arabidopsis was mainly contributed by whole-genome duplications that occurred sometime after their split with the papaya. Though a role of transposed duplication was also observed, tandem duplication was shown to be a key contributor in gene expansion of most species examined. Further comparative analyses of exon-intron structures and protein motifs supported fast evolution of this special superfamily, especially in Arabidopsis. Transcriptional profiling revealed diverse expression patterns of CpLEA genes over various tissues and different stages of developmental fruit. Moreover, the transcript level of most genes appeared to be significantly regulated by drought, cold, and salt stresses, corresponding to the presence of cis-acting elements associated with stress response in their promoter regions. These findings not only improve our knowledge on lineage-specific family evolution in Brassicales, but also provide valuable information for further functional analysis of LEA genes in papaya.

Corrigendum: Dosage Modification of Traditional Chinese Medicine Prescriptions: An Analysis of Two Randomized Controlled Trials.

[This corrects the article DOI: 10.3389/fphar.2021.732698.].

Case report: Treatment with Pien-Tze-Huang for prolonged positive SARS-CoV-2 test results in COVID-19 patients: A report of five cases.

Coronavirus disease 2019 (COVID-19) has rapidly spread around the world since December 2019, becoming a global pandemic. Atypical cases of COVID-19, manifesting as prolonged positive SARS-CoV-2 test results during the convalescence period, have been encountered. These cases increase the difficulty of COVID-19 prevention and treatment. Here, we report five cases of COVID-19 patients who demonstrated prolonged positive SARS-CoV-2 tests after regular traditional Chinese medicine and western medicine treatments. After administration of Pien-Tze-Huang and cessation of previous treatments, SARS-CoV-2 tests results of the patients turned and remained negative. We believe the finding will contribute to a better understanding of atypical COVID-19 cases and hope to offer a potential therapy. Since this is a preliminary case series, larger-scale clinical trials are warranted.

Controlled co-immobilisation of proteins via 4'-phosphopantetheine-mediated site-selective covalent linkage.

In Escherichia coli, acyl carrier protein (ACP) is posttranslationally converted into its active holo-ACP form via covalent linkage of 4'-phosphopantetheine (4'-PP) to residue serine-36. We found that the long flexible 4'-PP arm could react chemoselectively with the iodoacetyl group introduced on solid supports with high efficiency under mild conditions. Based on this finding, we developed site-selective immobilisation of proteins via the active holo-ACP fusion tag, independently of the physicochemical properties of the protein of interest. Furthermore, the molecular ratios of co-immobilised proteins can be manipulated because the tethering process is predominantly directed by the molar concentrations of diverse holo-ACP fusions during co-immobilisation. Conveniently tuning the molecular ratios of co-immobilised proteins allows their cooperation, leading to a highly productive multi-protein co-immobilisation system. Kinetic studies of enzymes demonstrated that α-amylase (Amy) and methyl parathion hydrolase (MPH) immobilised via active tag holo-ACP had higher catalytic efficiency (kcat/Km) in comparison with their corresponding counterparts immobilised via the sulfhydryl groups (-SH) of these proteins. The immobilised holo-ACP-Amy also presented higher thermostability compared with free Amy. The enhanced α-amylase thermostability upon immobilisation via holo-ACP renders it more suitable for industrial application.

Efficacy and safety of a Chinese herbal formula Maxing Ganshi Decoction in children with community-acquired pneumonia: A randomized, double-blind, placebo-controlled, multicenter trial.

Background: As one of the most commonly used Chinese medicine formula in the manage of respiratory diseases, Maxing Ganshi Decoction (MGD) has been demonstrated to improve the clinical symptoms of pneumonia. To evaluate the efficacy and safety of MGD in treating children with community-acquired pneumonia (CAP), we conducted the clinical trial. Methods: A randomized, double-blind, placebo-controlled, multicenter trial was conducted in 3 study sites in Tianjin, China. MDG or placebo were randomly given to patients aged 3-6 years with onset of CAP within 48 h. Changes in disease efficacy during the study period (which was measured as recovery, significant effect, improvement and no effect) was evaluated as the primary outcome. Time from enrollment to fever resolution was assessed as the secondary outcome. The adverse event was analyzed as safety evaluation. Results: A total of 71 patients (36 in MGD and 35 in placebo) were randomized and completed the whole study. The patient demographics and other characteristics at baseline were similar between the 2 groups (p > 0.05). After 10 days of intervention, the proportion of recovered and significant effective patients was increased significantly in the MGD group (34.85% [95% CI, 12.44%-57.26%]; p < 0.05) compared with the control group. Besides, the symptom score of the MGD group was lowered significantly (p < 0.001). The estimated time to fever resolution in the MGD group was also reduced compared with the control group (p < 0.05). During the whole study, no side effects were observed in both MGD and control groups. Conclusion: MGD was effective in improving disease efficacy, clinical symptoms and reducing time to fever resolution in patients with childhood CAP, which suggested that MGD may be used as an alternative therapy in the treatment of childhood CAP. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=5612, identifier 13003955.

Effect of traditional Chinese medicine on gut microbiota in adults with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: Despite advances in research on type 2 diabetes mellitus (T2DM) with the development of science and technology, the pathogenesis and treatment response of T2DM remain unclear. Recent studies have revealed a significant role of the microbiomein the development of T2DM, and studies have found that the gut microbiota may explain the therapeutic effect of traditional Chinese medicine (TCM), a primary branch of alternative and complementary medicine, in the treatment of T2DM. The aim of this study was to systematically review all randomized controlled trials (RCTs) on TCM for gut microbiota to assess the effectiveness and safety of TCM in T2DM patients. METHODS: All RCTs investigating the effects of TCM interventions on modulating gut microbiota and improving glucose metabolism in the treatment of T2DM adults were included. Meta-analyses were conducted when sufficient data were available, other results were reported narratively. The study protocol was pre-specified, documented, and published in PROSPERO (registration no. CRD42020188043). RESULTS: Five studies met the eligibility criteria ofthe systematic review. All five studies reported the effects of TCM interventions on the gut microbiota modulation and blood glucose control. There were statistically significant improvements in HbA1c (mean difference [MD]: -0.69%; [95% CI -0.24, -0.14]; p = 0.01, I2 = 86%), fasting blood glucose (MD: -0.87 mmol/l; [95% CI -1.26, -0.49]; p < 0.00001, I2 = 75%) and 2-h postprandial blood glucose(MD: -0.83mmol/l; [95% CI: -1.01, -0.65]; p < 0.00001, I2 = 0%). In addition, there were also statistically significant improvements in homeostasis model assessment of insulin resistance (HOMA-IR) (standardized mean difference [SMD]: -0.99, [95% CI -1.25 to -0.73]; p < 0.00001, I2 = 0%) and homeostasis model assessment of ß-cell function (HOMA-ß) (SMD: 0.54, [95% CI 0.21 to 0.87]; p = 0.001, I2 = 0%).There was a significant change in the relative abundance of bacteria in the genera Bacteroides (standardized mean difference [SMD] 0.87%; [95% CI 0.58, 1.16], however, the change in Enterococcus abundance was not statistically significant (SMD: -1.71%; [95% CI: -3.64, 0.23]; p = 0.08) when comparing TCM supplementaltreatment with comparator groups. Other changes in the gut microbiota, including changes in the relative abundances of some probiotics and opportunistic pathogens at various taxon levels, and changes in diversity matrices (α and ß), were significant by narrative analysis. However, insufficient evidences were found to support that TCM intervention had an effect on inflammation. CONCLUSION: TCM had the effect of modulating gut microbiota and improving glucose metabolisms in T2DM patients. Although the results of the included studies are encouraging, further well-conducted studies on TCM interventions targeting the gut microbiota are needed.