The calcium-dependent protein kinase CPK28 is targeted by the ubiquitin ligases ATL31 and ATL6 for proteasome-mediated degradation to fine-tune immune signaling in Arabidopsis.

Immune responses are triggered when pattern recognition receptors recognize microbial molecular patterns. The Arabidopsis (Arabidopsis thaliana) receptor-like cytoplasmic kinase BOTRYTIS-INDUCED KINASE1 (BIK1) acts as a signaling hub of plant immunity. BIK1 homeostasis is maintained by a regulatory module in which CALCIUM-DEPENDENT PROTEIN KINASE28 (CPK28) regulates BIK1 turnover via the activities of two E3 ligases. Immune-induced alternative splicing of CPK28 attenuates CPK28 function. However, it remained unknown whether CPK28 is under proteasomal control. Here, we demonstrate that CPK28 undergoes ubiquitination and 26S proteasome-mediated degradation, which is enhanced by flagellin treatment. Two closely related ubiquitin ligases, ARABIDOPSIS TÓXICOS EN LEVADURA31 (ATL31) and ATL6, specifically interact with CPK28 at the plasma membrane; this association is enhanced by flagellin elicitation. ATL31/6 directly ubiquitinate CPK28, resulting in its proteasomal degradation. Furthermore, ATL31/6 promotes the stability of BIK1 by mediating CPK28 degradation. Consequently, ATL31/6 positively regulate BIK1-mediated immunity. Our findings reveal another mechanism for attenuating CPK28 function to maintain BIK1 homeostasis and enhance immune responses.

An observational study of the pH value during the healing process of diabetic foot ulcer.

OBJECTIVE: In this study, we evaluated the pH (potential of hydrogen) value of diabetic foot ulcers and explored the relationship between the pH value and infection, sinus formation, stasis dermatitis, and the process of healing. METHODS: From October 2022 to June 2023, 99 patients with 106 diabetic foot ulcers were selected. Diabetic foot ulcers were treated in a standardized manner by a professional team. The pH value, area, PUSH (Pressure Ulcer Scale for Healing) score, and the degree of infection of the wounds were compared before and after the treatment. RESULTS: The baseline wound pH value in 76.4% of the patients was in the alkaline range and was closely related to the degree of infection (P < 0.05). As the ulcers healed, the pH decreased. For moderately and severely infected diabetic foot ulcers, each unit decrease in pH was associated with a decrease in the PUSH score of approximately 4.6 points (P < 0.05). The pH values of wounds with surrounding ecchymosis dermatitis were significantly higher than those of wounds without ecchymosis dermatitis (P < 0.05). The pH value of the wound with a sinus tract was higher. After treatment, there was no significant difference in pH value between the patients with and without sinus tracts (P < 0.05). CONCLUSIONS: The measurement of pH value is efficient and simple, and the patient suffers no discomfort in the process. The change in pH helps predict the healing process of diabetic foot ulcers and quickly identify whether there are key factors such as infection and ischemia in the wound. It is suggested that dynamic pH monitoring be included in the whole course evaluation and intervention strategy development of diabetic foot.

Dual-Ligand-Functionalized Liposomes Based on Glycyrrhetinic Acid and cRGD for Hepatocellular Carcinoma Targeting and Therapy.

Hepatocellular carcinoma (HCC) is one of the most common cancers, with high mortality. Chemotherapy is one of the main treatment options for HCC. However, the high toxicity and poor specificity of chemotherapeutic drugs have limited their clinical application. In this study, dual-ligand liposomes modified with glycyrrhetinic acid (GA) and cyclic arginine-glycine-aspartic acid (cRGD) (GA/cRGD-LP) were designed to target the GA receptor and αvß3 integrin, respectively. The aim was to develop a highly selective targeted drug delivery system and further enhance the antitumor efficiency of drugs by targeting both hepatic tumor cells and vasculature. A novel lipid conjugate (mGA-DOPE) by coupling dioleoylphosphatidyl ethanolamine (DOPE) with methyl glycyrrhetinic acid (mGA) was synthesized, and its structure was confirmed. The targeting efficiency of GA/cRGD-LP by in vitro cellular uptake and ex vivo imaging was assessed. GA- and cRGD-modified doxorubicin-loaded liposomes (GA/cRGD-LP-DOX) were prepared, and their cytotoxicity in HepG2 and antitumor activity were evaluated. The results showed that the average particle size of the GA/cRGD-LP-DOX was 114 ± 4.3 nm, and the zeta potential was -32.9 ± 2.0 mV. The transmission electron microscopy images showed that the shapes of our liposomes were spherical. cGA/cRGD-LP-DOX displayed an excellent cellular uptake in both HepG2 and human umbilical vein endothelial cells. In the in vivo study, pharmacokinetic parameters indicated that cGA/cRGD-LP can prolong the circulation time of DOX in the blood. GA/cRGD-LP-DOX showed greater inhibition of tumor growth for HepG2-bearing mice than either the single-ligand-modified liposomes or nontargeted liposomes. GA/cRGD-LP-DOX displayed higher liver tumor localization than that of single-ligand-modified liposomes or free DOX. GA/cRGD-LP is a promising drug delivery system for liver cancer targeting and therapy and is worthy of further study.

Survey of factors related to diabetic foot pruritus in the elderly in Shanghai.

The objective of the study is to explore the status quo of foot pruritus and related factors in elderly diabetics and provide a reference for targeted preventive measures. The study involved a survey using a self-designed foot pruritus assessment scale to understand the status quo of foot pruritus among 411 cases of elderly diabetics from 5 communities in Shanghai. The morbidity rate of foot pruritus in elderly diabetics in the community was 20.1%. Good self-management behaviour was the protective factor, while diabetic peripheral neuropathy, hyperlipidemia, and dry skin were risk factors (all P < 0.05). The incidence of foot pruritus in elderly diabetics was high and influenced by several factors. We recommend that self-management behaviour of patients be improved. Additionally, screening and interventions to address hyperlipidemia, diabetic peripheral neuropathy, and dry skin should be conducted regularly to prevent diabetic foot ulcers.

A receptor-like cytoplasmic kinase PCRK2 undergoes ubiquitination and proteasomal degradation.

Receptor-like cytoplasmic kinase (RLCK) subfamily VII members are involved in diverse biological processes, like reproduction, immunity, growth and development. Ubiquitination and proteasomal degradation of a RLCK VII member, BOTRYTIS-INDUCED KINASE1 (BIK1) play important roles in regulating immune signaling. It remains largely unknown whether most other RLCK VII members undergo ubiquitination and proteasomal degradation. Here, we select the 6-member RLCK VII-4 to examine the potential proteasomal degradation of its members. We find that three closely related RLCK VII-4 members, PBL38 (AvrPphB SUSCEPTIBLE1-LIKE38), PCRK1 (PTI-COMPROMISED RECEPTOR-LIKE CYTOPLASMIC KINASE1), and PCRK2 are under proteasomal control, while the other members in this group are not. Moreover, we demonstrate that PCRK2 undergoes ubiquitination and proteasomal in a kinase activity-dependent manner. However, the plasma membrane (PM) localization of PCRK2 is not required for its degradation. Our work suggests that many other RLCK VII members may undergo ubiquitination and proteasomal degradation to modulate their homeostasis and cellular functions.

Natural variation in the HAN1 gene confers chilling tolerance in rice and allowed adaptation to a temperate climate.

Rice (Oryza sativa L.) is a chilling-sensitive staple crop that originated in subtropical regions of Asia. Introduction of the chilling tolerance trait enables the expansion of rice cultivation to temperate regions. Here we report the cloning and characterization of HAN1, a quantitative trait locus (QTL) that confers chilling tolerance on temperate japonica rice. HAN1 encodes an oxidase that catalyzes the conversion of biologically active jasmonoyl-L-isoleucine (JA-Ile) to the inactive form 12-hydroxy-JA-Ile (12OH-JA-Ile) and fine-tunes the JA-mediated chilling response. Natural variants in HAN1 diverged between indica and japonica rice during domestication. A specific allele from temperate japonica rice, which gained a putative MYB cis-element in the promoter of HAN1 during the divergence of the two japonica ecotypes, enhances the chilling tolerance of temperate japonica rice and allows it to adapt to a temperate climate. The results of this study extend our understanding of the northward expansion of rice cultivation and provide a target gene for the improvement of chilling tolerance in rice.

Histone deacetylase 6 promotes skin wound healing by regulating fibroblast migration and differentiation in aged mice.

Skin wound healing tends to slow down with aging, which is detrimental to both minor wound recovery in daily life and the recovery after surgery. The aim of current study was to explore the effect of histone deacetylase 6 (HDAC6) on wound healing during aging. Cultured human dermal fibroblasts (HDFs) and mouse full-thickness skin wound model were used to explore the functional changes of replicative senescent dermal fibroblasts and the effect of aging on skin wound healing. Scratch wound healing assay revealed significantly decreased migration speed of senescent HDFs, and BrdU incorporation assay indicated their considerably retardant proliferation. The protein expression levels of collagen and HDAC6 were significantly decreased in both senescent HDFs and skin tissues from aged mice. HDAC6 activity inhibition with highly selective inhibitor tubastatin A (TsA) or HDAC6 knockdown with siRNA decreased the migration speed of HDFs and considerably suppressed fibroblast differentiation induced by transforming growth factor-ß1 (TGF-ß1), which suggests the involvement of HDAC6 in regulating fundamental physiological activities of dermal fibroblasts. In vivo full-thickness skin wound healing was significantly delayed in young HDAC6 knockout mice when compared with young wild type mice. In addition, the wound healing was significantly slower in aged wild type mice than that in young wild type mice, and became even worse in aged HDAC6 knockout aged mice. Compared to the aged wild type mice, aged HDAC6 knockout mice exhibited delayed angiogenesis, reduced collagen synthesis, and decreased collagen deposition in skin wounds. Together, these results suggest that delayed skin wound healing in aged mice is associated with impaired fibroblast function. Adequate expression and activity of HDAC6 are required for fibroblasts migration and differentiation.

Transcriptional Regulation of the Immune Receptor FLS2 Controls the Ontogeny of Plant Innate Immunity.

Innate immunity plays a vital role in protecting plants and animals from pathogen infections. Immunity varies with age in both animals and plants. However, little is known about the ontogeny of plant innate immunity during seedling development. We report here that the Arabidopsis (Arabidopsis thaliana) microRNA miR172b regulates the transcription of the immune receptor gene FLAGELLIN-SENSING2 (FLS2) through TARGET OF EAT1 (TOE1) and TOE2, which directly bind to the FLS2 promoter and inhibit its activity. The level of miR172b is very low in the early stage of seedling development but increases over time, which results in decreased TOE1/2 protein accumulation and, consequently, increased FLS2 transcription and the ontogeny of FLS2-mediated immunity during seedling development. Our study reveals a role for the miR172b-TOE1/2 module in regulating plant innate immunity and elucidates a regulatory mechanism underlying the ontogeny of plant innate immunity.plantcell;30/11/2779/FX1F1fx1.

A novel 4-mRNA signature predicts the overall survival in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive cancer of myeloid cells with high levels of heterogeneity and great variability in prognostic behaviors. Cytogenetic abnormalities and genetic mutations have been widely used in the prognostic stratification of AML to assign patients into different risk categories. Nevertheless, nearly half of AML patients assigned to intermediate risk need more precise prognostic schemes. Here, 336 differentially expressed genes (DEGs) between AML and control samples and 206 genes representing the intratumor heterogeneity of AML were identified. By applying a LASSO Cox regression model, we generated a 4-mRNA prognostic signature comprising KLF9, ENPP4, TUBA4A and CD247. Higher risk scores were significantly associated with shorter overall survival, complex karyotype, and adverse mutations. We then validated the prognostic value of this 4-mRNA signature in two independent cohorts. We also proved that incorporation of the 4-mRNA-based signature in the 2017 European LeukemiaNet (ELN) risk classification could enhance the predictive accuracy of survival in patients with AML. Univariate and multivariate analyses showed that this signature was independent of traditional prognostic factors such as age, WBC count, and unfavorable cytogenetics. Finally, the molecular mechanisms underlying disparate outcomes in high-risk and low-risk AML patients were explored. Therefore, our findings suggest that the 4-mRNA signature refines the risk stratification and prognostic prediction of AML patients.

Construction and verification of an intelligent measurement model for diabetic foot ulcer. / ä¸€ç§ç³–å°¿ç— è¶³æºƒç–¡æ™ºèƒ½æµ‹é‡æ¨¡åž‹çš„æž„å»ºä¸ŽéªŒè¯.

OBJECTIVES: The measurement of diabetic foot ulcers is important for the success in diabetic foot ulcer management. At present, it lacks the accurate and convenient measurement tools in clinical. In recent years, artificial intelligence technology has demonstrated the potential application value in the field of image segmentation and recognition. This study aims to construct an intelligent measurement model of diabetic foot ulcers based on the deep learning method, and to conduct preliminary verification. METHODS: The data of 1 042 diabetic foot ulcers clinical samples were collected. The ulcers and color areas were manually labeled, of which 782 were used as the training data set and 260 as the test data set. The Mask RCNN ulcer tissue color semantic segmentation and RetinaNet scale digital scale target detection were used to build a model. The training data set was input into the model and iterated. The test data set was used to verify the intelligent measurement model. RESULTS: This study established an intelligent measurement model of diabetic foot ulcers based on deep learning. The mean average precision@.5 intersection over union (mAP@.5IOU) of the color region segmentation in the training set and the test set were 87.9% and 63.9%, respectively; the mAP@.5IOU of the ruler scale digital detection in the training set and the test set were 96.5% and 83.4%, respectively. Compared with the manual measurement result of the test sample, the average error of the intelligent measurement result was about 3 mm. CONCLUSIONS: The intelligent measurement model has good accuracy and robustness in measuring the diabetic foot ulcers. Future research can further optimize the model with larger-scale data samples.

Cotargeting the JAK/STAT signaling pathway and histone deacetylase by ruxolitinib and vorinostat elicits synergistic effects against myeloproliferative neoplasms.

The majority of patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) harbor a gain of function mutation V617F in Janus kinase (JAK) 2. Although JAK2 inhibitors such as ruxolitinib have been shown to be clinically efficacious, the hematological toxicity and eventual drug resistance limit its use as monotherapy. Other gene mutations or dysregulation correlated with the disease phenotype and prognosis have been found to contribute to the complexity and heterogeneity of MPNs, giving rise to an increasing demand for combination therapies. Here, we combine ruxolitinib and the histone deacetylase inhibitor vorinostat as a rational combination strategy for MPNs. We tested the combination of ruxolitinib and vorinostat in cells with the JAK2V617F mutation, such as HEL cells, c-Kit+ cells from JAK2V617F transgenic mice and bone marrow mononuclear cells (BMMNCs) from patients with MPN. Our results showed significant synergistic effects of this combination strategy. Cotreatment with ruxolitinib and vorinostat synergistically induced apoptosis, cell cycle arrest and inhibition of the colony-forming capacity of HEL cells by attenuating the JAK/signal transducer and activator of transcription (STAT) and protein kinase-B (AKT) signaling pathways. In particular, cotreatment with ruxolitinib and vorinostat prevented the formation of large colonies of colony-forming unit-granulocyte/erythroid/macrophage/megakaryocytes (CFU-GEMMs) and colony-forming unit-granulocyte/macrophages (CFU-GMs) derived from the BMMNCs of patients with MPN. Taken together, these data provided preclinical evidence that the combination of ruxolitinib and vorinostat is a potential dual-target therapy for patients with MPN.

Identification of critical cysteine sites in brassinosteroid-insensitive 1 and novel signaling regulators using a transient expression system.

The plant hormones brassinosteroids (BRs) modulate plant growth and development. Cysteine (Cys) residues located in the extracellular domain of a protein are of importance for protein structure by forming disulfide bonds. To date, the systematic study of the functional significance of Cys residues in BR-insensitive 1 (BRI1) is still lacking. We used brassinolide-induced exogenous bri1-EMS-Suppressor 1 (BES1) dephosphorylation in Arabidopsis thaliana protoplasts as a readout, took advantage of the dramatic decrease of BRI1 protein levels during protoplast isolation, and of the strong phosphorylation of BES1 by BR-insensitive 2 (BIN2) in protoplasts, and developed a protoplast transient system to identify critical Cys sites in BRI1. Using this system, we identified a set of critical Cys sites in BRI1, as substitution of these Cys residues with alanine residues greatly compromised the function of BRI1. Moreover, we identified two negative regulators of BR signaling, pattern-triggered immunity compromised RLCK1 (PCRK1) and PCRK2, that were previously known to positively regulate innate immunity signaling. This work not only provides insight into the functional importance of critical Cys residues in stabilizing the superhelical conformation of BRI1-leucine-rich-repeat, but also reveals that PCRK1/2 can inversely modulate BR and plant immune signaling pathways.

Efficacy of Biomechanics-based Decompression Therapy in Managing Recurrent Diabetic Plantar Ulcers.

OBJECTIVE: The objective of this study is to assess the efficacy of decompression nursing based on biomechanical principles in managing recurrent diabetic plantar ulcers. METHODS: Sixty-seven patients experiencing recurrent diabetic plantar ulcers who sought medical attention at Huadong Hospital Affiliated to Fudan University between January 2021 and December 2022 were selected as participants for this study. The participants underwent biomechanics-based decompression nursing. We compared pre-intervention and post-intervention data to assess the differences in relevant observational indexes. RESULTS: Post-intervention, patients showed significant improvements in foot comfort scores and adherence to pressure reduction behavior compared with their pre-intervention status, with statistical significance (P < 0.05). The intervention was effective in 41 cases (61.19%), with 18 cases (26.87%) showing improvement and 8 cases (11.94%) deemed ineffective, culminating in an overall efficacy rate of 88.06%. All 67 patients achieved complete ulcer healing within an average duration of 58.63 ± 18.13 days, without any recorded recurrences. CONCLUSION: Biomechanics-based decompression nursing demonstrates effective facilitation of wound healing, yielding expeditious recovery, enhanced comfort, and a reduced incidence of recurrence.

Promoting tissue repair using deferoxamine nanoparticles loaded biomimetic gelatin/HA composite hydrogel.

To effectively address underlying issues and enhance the healing process of hard-to-treat soft tissue defects, innovative therapeutic approaches are required. One promising strategy involves the incorporation of bioactive substances into biodegradable scaffolds to facilitate synergistic tissue regeneration, particularly in vascular regeneration. In this study, we introduce a composite hydrogel design that mimics the extracellular matrix by covalently combining gelatin and hyaluronic acid (HA), with the encapsulation of deferoxamine nanoparticles (DFO NPs) for potential tissue regeneration applications. Crosslinked hydrogels were fabricated by controlling the ratio of HA in the gelatin-based hydrogels, resulting in improved mechanical properties, enhanced degradation ability, and optimised porosity, compared with hydrogel formed by gelatin alone. The DFO NPs, synthesized using a double emulsion method with poly (D,L-lactide-co-glycolide acid), exhibited a sustained release of DFO over 12 d. Encapsulating the DFO NPs in the hydrogel enabled controlled release over 15 d. The DFO NPs, composite hydrogel, and the DFO NPs loaded hydrogel exhibited excellent cytocompatibility and promoted cell proliferationin vitro. Subcutaneous implantation of the composite hydrogel and the DFO NPs loaded hydrogel demonstrated biodegradability, tissue integration, and no obvious adverse effects, evidenced by histological analysis. Furthermore, the DFO NPs loaded composite hydrogel exhibited accelerated wound closure and promoted neovascularisation and granular formation when tested in an excisional skin wound model in mice. These findings highlight the potential of our composite hydrogel system for promoting the faster healing of diabetes-induced skin wounds and oral lesions through its ability to modulate tissue regeneration processes.

Application of a Diabetic Foot Smart APP in the measurement of diabetic foot ulcers.

AIMS: In the early stage, we developed an intelligent measurement APP for diabetic foot ulcers, named Diabetic Foot Smart APP. This study aimed to validate the APP in the measurement of ulcer area for diabetic foot ulcer (DFU). METHODS: We selected 150 DFU images to measure the ulcer areas using three assessment tools: the Smart APP software package, the ruler method, and the gold standard Image J software, and compared the measurement results and measurement time of the three tools. The intra-rater and inter-rater reliability were described by Pearson correlation coefficient, intra-group correlation coefficient, and coefficient of variation. RESULTS: The Image J software showed a median ulcer area of 4.02 cm2, with a mean measurement time of 66.37 ± 7.95 s. The ruler method showed a median ulcer area of 5.14 cm2, with a mean measurement time of 171.47 ± 46.43 s. The APP software showed a median ulcer area of 3.70 cm2, with a mean measurement time of 38.25 ± 6.81 s. There were significant differences between the ruler method and the golden standard Image J software (Z = -4.123, p < 0.05), but no significant difference between the APP software and the Image J software (Z = 1.103, p > 0.05). The APP software also showed good inter-rater reliability and intra-rater reliability, with both reaching 0.99. CONCLUSION: The Diabetic Foot Smart APP is a fast and reliable measurement tool with high measurement accuracy that can be easily used in clinical practice for the measurement of ulcer areas of DFU. TRIAL REGISTRATION: Chinese clinical trial registration number: ChiCTR2100047210.

SlbHLH22-Induced Hypertrophy Development Is Related to the Salt Stress Response of the GTgamma Gene in Tomatoes.

Hypertrophy development induced by the overexpression of SlbHLH22 (also called SlUPA-like) was susceptible to Xanthomonas in tomatoes. Transcriptome and metabolome analyses were performed on the hypertrophy leaves of a SlbHLH22-overexpressed line (OE) and wild type (WT) to investigate the molecular mechanism. Metabolome analysis revealed that six key metabolites were over-accumulated in the OE, including Acetylserine/O-Acetyl-L-serine, Glucono-1,5-lactone, Gluconate, 2-Oxoglutarate, and Loganate, implying that the OE plants increased salt or oxidant resistance under normal growth conditions. The RNA-seq analysis showed the changed expressions of downstream genes involved in high-energy consumption, photosynthesis, and transcription regulation in OE lines, and we hypothesized that these biological processes were related to the GTgamma subfamily of trihelix factors. The RT-PCR results showed that the expressions of the GTgamma genes in tomatoes, i.e., SlGT-7 and SlGT-36, were suppressed in the hypertrophy development. The expression of the GTgamma gene was downregulated by salinity, indicating a coordinated role of GTgamma in hypertrophy development and salt stress. Further research showed that both SlGT-7 and SlGT-36 were highly expressed in leaves and could be significantly induced by abscisic acid (ABA). The GTgamma protein had a putative phosphorylation site at S96. These results suggested GTgamma's role in hypertrophy development by increasing the salt resistance.

A 15-year follow-up report of an elderly diabetic foot with multiple recurrences leading to toe amputation and thoughts on the model of care for diabetic foot ulcer.

Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes. Elderly diabetic patients are a high prevalence of diabetic foot ulcers, and their high recurrence, disability, and mortality rates impose a heavy economic burden on families and society. This paper reports a case of an elderly patient with a diabetic foot ulcer who was admitted in April 2007 and discharged after recovery from comprehensive diabetic foot treatment. Due to intermittent foot care and lack of home care, the patient's foot ulcers recurred after repeated healing during home rehabilitation, eventually resulting in the amputation of the right bunion. After the patient was discharged from the hospital with an amputated toe, the whole-process seamless management model of "hospital - community - family" was implemented. The hospital provides specialized foot support and guidance, and the community is responsible for daily disease management and referrals. The family is responsible for the implementation of home rehabilitation programs, and family caregivers need to identify and provide feedback on foot abnormalities promptly. As of May 2022, the patient had not experienced ulcer recurrence. This paper reports the whole process of "ulcer development → ulcer healing → ulcer recurrence healing → toe amputation → continuous care management" experienced by the patient in 15 years, aiming to reflect on the significance of the whole-process seamless foot care management model of "hospital-community-family" for diabetic foot ulcer rehabilitation through the case.

Perceptions of protective shoes and recommendations from patients with diabetic foot ulcers.

Development of diabetic foot can cause serious harm to a patient's body and pose a heavy burden on family members and society. Protective shoes are of great significance to preventing diabetic foot. The aim of the current study was to understand patients' views and suggestions concerning the selection and promotion of protective shoes for diabetics in order to explore existing obstacles and to provide a reference for improving relevant public health care policies and clinical decision-making for patients with diabetic foot ulcers (DFUs). A total of 10 patients with DFUs were recruited. All participants completed a one-hour semi-structured interview, and results reflected the participants' choice of footwear, the patients' perceptions and acceptance of protective footwear, and factors influencing those processes. The use and promotion of protective shoes in China requires greater support, including improved medical insurance policies, promotion of multidisciplinary cooperation between medicine and industry in clinical practice, and better health education.

Effect of COVID-19 on Menstruation and Lower Reproductive Tract Health.

Background: To evaluate the dynamically impact of the coronavirus disease 2019 (COVID-19) on the female reproductive system. Methods: An online survey was shared to women of reproductive age who had been infected with COVID-19 and recovered in China between January and March 2023. Results: In total, 610 women of childbearing age completed the menstrual component of the survey and 82.6% (n=504) women self-purchased medications without hospitalization. 254 women were menstruating during COVID-19 infection. 66.9% of them reported changes in menstruation, including cycle length (64.7%), menstrual flow (72.4%), and duration (53%), compared to pre-COVID-19. COVID-19-related chest tightness (OR: 9.5; 95% CI: 1.9-46.3), COVID-19-related stress (OR: 18.4; 95% CI: 1.4-249.7), and COVID-19-related low mood (OR: 6.2; 95% CI: 1.4-28.2) were associated with these menstrual changes. However, over 73% of women who menstruated during and after COVID-19 regained their pre-infection menstrual cycle (73%), duration (79.6%), and flow (75.2%) during their first menstruation after COVID-19 recovery. Compared to pre-infection, 19.7% (n=124) women reported changes in lower reproductive tract during COVID-19, including volume and color of vaginal discharge, vulvar pruritus, and vaginitis. These changes were significantly increased in those with a history of pelvic inflammatory disease (OR: 12.1; 95% CI: 3.1-48.2), ovarian cysts (OR: 4.9; 95% CI: 1.2-19.4), and vaginitis (OR: 5.5; 95% CI: 2.1-14.4) prior to COVID-19. However, 52.4% reported that their lower reproductive tract health had returned to its pre-infection within the first month after recovery from COVID-19, while 73.5% reported a return to the pre-infection within 2 months. Conclusion: Changes in menstruation and lower reproductive tract associated with COVID-19 are transient. Menstruation and lower reproductive tract health will gradually return to pre-COVID-19 status within 2 months of recovery, which can help alleviate excessive concerns about the effects of COVID-19 on the reproductive system.

The enzymatic hydrolysate of fucoidan from Sargassum hemiphyllum triggers immunity in plants.

Fucoidans are polysaccharides that consist predominantly of sulfated L-fucoses, from which, fucoidan oligosaccharides (FOSs) are prepared through different methods. Fucoidan has versatile physiological activities, like antiviral functions against SARS CoV-2 and bioactivitiy in enhancing immune responses. Although fucoidan or FOS has been widely used in mammals as functional foods and new drugs, its application in plants is still very limited. Moreover, whether fucoidan or its derived hydrolytic products can trigger immune responses in plants remained unknown. In this work, we demonstrate that the fucoidan enzymatic hydrolysate (FEH) prepared from Sargassum hemiphyllum triggers various immune responses, such as ROS production, MAPK activation, gene expression reprogramming, callose deposition, stomatal closure, and plant resistance to the bacterial strain Pseudomonas syringae pv. tomato (Pst) DC3000. Notably, FEH did not induce Arabidopsis root growth inhibition at the concentration used for triggering other immune responses. Our work suggests that EHF can potentially be used as a non-microbial elicitor in agricultural practices to protect plants from pathogen infection.