Genome-wide analysis and expression profiling of the HD-ZIP gene family in kiwifruit.

The homeodomain-leucine zipper (HD-Zip) gene family plays a pivotal role in plant development and stress responses. Nevertheless, a comprehensive characterization of the HD-Zip gene family in kiwifruit has been lacking. In this study, we have systematically identified 70 HD-Zip genes in the Actinidia chinensis (Ac) genome and 55 in the Actinidia eriantha (Ae) genome. These genes have been categorized into four subfamilies (HD-Zip I, II, III, and IV) through rigorous phylogenetic analysis. Analysis of synteny patterns and selection pressures has provided insights into how whole-genome duplication (WGD) or segmental may have contributed to the divergence in gene numbers between these two kiwifruit species, with duplicated gene pairs undergoing purifying selection. Furthermore, our study has unveiled tissue-specific expression patterns among kiwifruit HD-Zip genes, with some genes identified as key regulators of kiwifruit responses to bacterial canker disease and postharvest processes. These findings not only offer valuable insights into the evolutionary and functional characteristics of kiwifruit HD-Zips but also shed light on their potential roles in plant growth and development.

Topical application of a novel anti-interleukin-17A antibody fragment penetrates psoriatic skin: Results of a randomised, double-blind, placebo-controlled Phase Ib study.

Interleukin (IL)-17A underlies the pathogenesis of chronic plaque psoriasis (CPP). Well-tolerated, effective IL-17A inhibitors for mild-to-moderate CPP are needed. ZL-1102 is a novel antibody fragment targeting IL-17A. To assess the safety, tolerability, preliminary efficacy and skin penetration of a topical 1% ZL-1102 hydrogel in patients with mild-to-moderate CPP, a two-part, Phase Ib study was conducted. Open-label Part A: six patients received a single topical application of ZL-1102 onto a psoriatic plaque; double-blind Part B: 53 patients were randomised 1:1 to twice-daily ZL-1102 or vehicle for 4 weeks. Key primary endpoints included treatment-emergent adverse events (TEAEs), tolerability and changes in local psoriasis area and severity index (PASI). TEAEs occurred in two (33.3%) patients in Part A and in 16 (59.3%) and 13 (50.0%) patients in the ZL-1102 and vehicle arms, respectively, in Part B. No grade ≥3 TEAEs were seen with ZL-1102. ZL-1102 led to numerically greater changes in local PASI versus vehicle (-28.8% vs. -17.2%), with good local tolerability. The trend towards local PASI improvement was accompanied by biomarker changes based on RNA sequencing, indicative of ZL-1102 penetration into psoriatic plaques. Topical ZL-1102 showed good safety, local tolerability and a trend towards improved local PASI; skin penetration was observed without measurable systemic exposure. ACTRN12620000700932.

Insight into microvascular adaptive alterations in the Glisson system of biliary atresia after Kasai portoenterostomy using X-ray phase-contrast CT.

OBJECTIVES: To investigate microvascular alterations in the Glisson system of biliary atresia (BA) patients after Kasai portoenterostomy (KP) using three-dimensional (3D) virtual histopathology based on X-ray phase-contrast CT (PCCT). METHODS: Liver explants from BA patients were imaged using PCCT, and 32 subjects were included and divided into two groups: KP (n = 16) and non-KP (n = 16). Combined with histological analysis and 3D visualization technology, 3D virtual histopathological assessment of the biliary, arterial, and portal venous systems was performed. According to loop volume ratio, 3D spatial density, relative surface area, tortuosity, and other parameters, pathological changes of microvasculature in the Glisson system were investigated. RESULTS: In the non-KP group, bile ducts mostly manifested as radial multifurcated hyperplasia and twisted into loops. In the KP group, the bile duct hyperplasia was less, and the loop volume ratio of bile ducts decreased by 13.89%. Simultaneously, the arterial and portal venous systems presented adaptive alterations in response to degrees of bile duct hyperplasia. Compared with the non-KP group, the 3D spatial density of arteries in the KP group decreased by 3.53%, and the relative surface area decreased from 0.088 ± 0.035 to 0.039 ± 0.015 (p < .01). Deformed portal branches gradually recovered after KP, with a 2.93% increase in 3D spatial density and a decrease in tortuosity from 1.17 ± 0.06 to 1.14 ± 0.04 (p < .01) compared to the non-KP group. CONCLUSION: 3D virtual histopathology via PCCT clearly reveals the microvascular structures in the Glisson system of BA patients and provides key insights into the morphological mechanism of microvascular adaptation induced by biliary tract dredging after KP in BA disease. KEY POINTS: • 3D virtual histopathology via X-ray phase-contrast computed tomography clearly presented the morphological structures and pathological changes of microvasculature in the Glisson system of biliary atresia patients. • The morphological alterations of microvasculature in the Glisson system followed the competitive occupancy mechanism in the process of biliary atresia.

Dry-Spinning of Artificial Spider Silk Ribbons From Regenerated Natural Spidroin in an Organic Medium.

Natural spider silks with striking performances achieve extensive investigations. Nonetheless, a lack of consensus over the mechanism of the natural spinning hinders the development of artificial spinning methods where the regenerated spider silks generally show poor performances compared with the natural fibers. As is known, the Plateau-Rayleigh instability tends to break solution column into droplets and is considered a main challenge during fiber-spinning. Here in this study, by harnessing the viscoelastic properties of the regenerated spidroin dope solution via organic salt-zinc acetate (ZA), this outcome can be avoided, and dry-spinning of long and mechanically robust regenerated spider silk ribbons can be successfully realized. The as-obtained dry-spun spider silk ribbons show an enhanced modulus up to 14 ± 4 GPa and a toughness of ≈51 ± 9 MJ m-3 after the post-stretching treatment, which is even better than that of the pristine spider silk fibers. This facile and flexible strategy enriches the spinning methodologies which bypass the bottleneck of precisely mimicking the complex natural environment of the glands in spiders, shining a light to the spider-silk-based textile industrial applications.

Molecular-Level Zn-Ion Transfer Pump Specifically Functioning on (002) Facets Enables Durable Zn Anodes.

The modification of metallic Zn anode contributes to solving the cycling issue of Zn-ion batteries (ZIBs) by restraining the dendrite growth and side reactions. In this regard, modulating (002) Zn is an effective way to prolong the lifespan of ZIBs with a parallel arrangement of Zn deposition. Herein, the authors propose to add trace amounts of Zn(BF4 )2 additive in 3 M ZnSO4 to promote in-plane Zn deposition by forming a BF4 - -[Zn(H2 O)6 ]2+ -[Zn(BF4 )3 ]- transfer process and specifically functioning on (002) facets. In this way, the optimized electrolyte highly boosts the cycling stability of Zn anodes with a long lifespan at 34.2% Zn utilization (500 h/10 mA cm-2 ) and 51.3% Zn utilization (360 h/10 mA cm-2 ; 834 h/1 mA cm-2 ). Moreover, the electroplated Zn on Cu substrate exhibits a competitive cumulative plating capacity (CPC) of 2.87 Ah cm-2 under harsh conditions. The assembled Zn|(NH4 )2 V6 O16 ·3H2 O full cells with a high cathode loading of 29.12 mg cm-2 also realizes almost no capacity degradation even after 2000 cycles at 2 A g-1 . With this cost-effective strategy, it is promising to push the development of aqueous ZIBs as well as provide inspiration for metal anode optimization in other energy storage systems.

MIR99AHG inhibits EMT in pulmonary fibrosis via the miR-136-5p/USP4/ACE2 axis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are closely related to the occurrence and development of cancer. Abnormally expressed lncRNA can be used as a diagnostic marker for cancer. In this study, we aim to investigate the clinical significance of MIR99AHG expression in lung adenocarcinoma (LUAD), and its biological roles in LUAD progression. METHODS: The relative expression of MIR99AHG in LUAD tissues and cell lines was analyzed using public databases and RT-qPCR. The biological functions of MIR99AHG were investigated using a loss-of-function approach. The effect of MIR99AHG on lung fibrosis was assessed by scratch assay, invasion assay and lung fibrosis rat model. FISH, luciferase reporter assay and immunofluorescence were performed to elucidate the underlying molecular mechanisms. RESULTS: LncRNA MIR99AHG expression level was downregulated in LUAD tissues and cell lines. Low MIR99AHG levels were associated with poorer patient overall survival. Functional analysis showed that MIR99AHG is associated with the LUAD malignant phenotype in vitro and in vivo. Further mechanistic studies showed that, MIR99AHG functions as a competitive endogenous RNA (ceRNA) to antagonize miR-136-5p-mediated ubiquitin specific protease 4 (USP4) degradation, thereby unregulated the expression of angiotensin-converting enzyme 2 (ACE2), a downstream target gene of USP4, which in turn affected alveolar type II epithelial cell fibrosis and epithelial-mesenchymal transition (EMT). In summary, the MIR99AHG/miR-136-5p/USP4/ACE2 signalling axis regulates lung fibrosis and EMT, thus inhibiting LUAD progression. CONCLUSION: This study showed that downregulated MIR99AHG leads to the development of pulmonary fibrosis. Therefore, overexpression of MIR99AHG may provide a new approach to preventing LUAD progression.

Interaction of MRPL9 and GGCT Promotes Cell Proliferation and Migration by Activating the MAPK/ERK Pathway in Papillary Thyroid Cancer.

Thyroid cancer remains the most common endocrine malignancy worldwide, and its incidence has steadily increased over the past four years. Papillary Thyroid Cancer (PTC) is the most common differentiated thyroid cancer, accounting for 80-85% of all thyroid cancers. Mitochondrial proteins (MRPs) are an important part of the structural and functional integrity of the mitochondrial ribosomal complex. It has been reported that MRPL9 is highly expressed in liver cancer and promotes cell proliferation and migration, but it has not been reported in PTC. In the present study we found that MRPL9 was highly expressed in PTC tissues and cell lines, and lentivirus-mediated overexpression of MRPL9 promoted the proliferation and migration ability of PTC cells, whereas knockdown of MRPL9 had the opposite effect. The interaction between MRPL9 and GGCT (γ-glutamylcyclotransferase) was found by immunofluorescence and co-immunoprecipitation experiments (Co-IP). In addition, GGCT is highly expressed in PTC tissues and cell lines, and knockdown of GGCT/MRPL9 in vivo inhibited the growth of subcutaneous xenografts in nude mice and inhibited the formation of lung metastases. Mechanistically, we found that knockdown of GGCT/MRPL9 inhibited the MAPK/ERK signaling pathway. In conclusion, our study found that the interaction of GGCT and MRPL9 modulates the MAPK/ERK pathway, affecting the proliferation and migration of PTC cells. Therefore, GGCT/MRPL9 may serve as a potential biomarker for PTC monitoring and PTC treatment.

Effects of A Benefit-Finding Intervention in Stroke Caregivers in Communities.

Objectives: To verify the effectiveness and feasibility of a nine-week benefit-finding intervention on the burden, quality of life, and benefit finding of caregivers, as well as on the quality of life of stroke survivors.Methods: Benefit finding refers to the individual, social, psychological and spiritual benefits perceived by an individual experiencing stress or post-traumatic events. A randomized controlled trial was performed in which 68 stroke survivors and their caregivers were recruited from the Zhengzhou community, China, and randomly split into two groups. The intervention group included those having undergone a nine-week benefit-finding intervention, while the control group included those individuals having undergone a nine-week routine health education. At baseline and one-week post-intervention (after a 9-week intervention), the quality of life of stroke survivors and caregivers and the burden and benefit finding of caregivers were determined.Results: In comparison to the control group, caregiver benefit finding, quality of life, burden, and stroke survivor quality of life were significantly improved (P <.005).Conclusions: The intervention appears to be feasible for stroke patients and caregivers. The intervention is capable of improving the quality of life of caregivers and survivors, increasing the benefit finding of caregivers and reducing the burden of caregivers.Clinical Implications: The benefit-finding intervention is capable of improving the health condition of stroke patients and caregivers.

Exploring polypharmacy burden among elderly patients with chronic diseases in Chinese community: a cross-sectional study.

BACKGROUND: In the long-term use of multiple medications for elderly patients diagnosed with chronic diseases, medication problems are prominent, which seriously reduces their quality of life. The burden of medications of patients critically affects their medication beliefs, behaviors and disease outcomes. It may be a solution to stress the burden of medications of patients. Its medication issues develops a novel perspective. The present study aimed to exploit the Chinese version of Living with Medicines Questionnaire-3(C-LMQ-3) to quantify the medicines burden of elderly patients diagnosed with chronic diseases in China, and evaluate the relevant demographic characteristics of sub-populations with high medicines burden. METHODS: The survey was distributed to elderly patients aged ≥ 60 years with chronic disease by using ≥ 5 medicines, C-LMQ-3 scores and domain scores were compared by the characteristics of elderly patients by employing descriptive statistics and performing statistical tests. RESULTS: On the whole, 430 responses were analyzed, and the participants were aged between 60 and 91 years, with the average age of 73.57 years (SD: 7.87). Most of the responses were female (61.7 %) with middle school education (38.5 %). Moreover, 54.1 % of the participants lived with spouse only, 16.2 % had both spouse and children, and 10.0 % lived alone. As indicated from regression analysis, higher C-LMQ-3 scores were associated with those who were with low education level, 60-69 years-old, using ≥ 11 medicines, using medicines ≥ 3 times a day, income per month (RMB) ≤ 3000, and who having higher monthly self-paid medication (RMB) ≥ 300 (p < 0.01). Burden was mainly driven by cost-related burden, concerns about medicines, and the lack of autonomy over medicine regimens. CONCLUSIONS: This study presents the preliminary evidence to elderly patients diagnosed with chronic diseases in mainland China that pay attention to multiple medications burden may help reduce the Drug Related Problems, whereas some elderly patients have a higher burden of medication. Chinese health care providers are required to primarily evaluate and highlight such patients, and formulate relevant intervention strategies to ensure medication adherence and daily medication management of elderly patients with polypharmacy.

Clinical outcomes of 402 patients with COVID-2019 from a single center in Wuhan, China.

The outbreak of SARS-CoV-2 has become a pandemic with significant mortality. Published studies described clinical characteristics of the disease contain small cohorts from individual centers or larger series consisting of mixed series from multiple different hospitals. We report here analyses of mortality and disease severity among 402 patients from a single hospital. The cohort includes 297 patients with confirmed and 105 with clinical diagnosis. The latter group consists of cases with inconclusive nucleic acid test but meeting the criteria for clinical diagnosis. Data are compared between sexes and among different age groups. The overall case fatality is 5.2%. However, age at 70 years or older is associated with a significantly higher mortality (17.8%) and higher rate of severe and critical illness (57.5%). Case fatality is 8% in patients 50 years of age or older, and 1.2% in those younger than 50 years. In addition, case fatality is 7.6% in male patients, as opposed to 2.9% in females, demonstrating a clear sex difference.