CXCL9 may serve as a potential biomarker for primary Sjögren's syndrome with extra-glandular manifestations.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune condition that causes harm to exocrine glands and also has extra-glandular manifestations (EGM). pSS patients with EGM have a worse prognosis than those with only sicca symptoms. Previous studies have shown that the minor salivary glands (MSG) of pSS patients exhibit a unique profile of cytokines and chemokines compared to healthy controls. However, there is a lack of research comparing pSS with EGM (pSS-EGM) and pSS without EGM (pSS-non-EGM). This study aims to explore potential biomarkers associated with pSS, particularly pSS with EGM. METHODS: By utilizing RNA sequencing, we conducted an analysis on the gene expression profiles of MSG in 63 patients diagnosed with pSS, as well as 12 non-pSS individuals. Furthermore, we also investigated the MSG of pSS patients, both with and without EGM. Through bioinformatics analysis, we identified genes with differential expression (DEGs) and determined the core hub genes using PPI network. We then analyzed the top 20 DEGs and their correlation with the patients' clinical characteristics, and validated our findings using peripheral blood plasma. RESULTS: A total of 725 differentially expressed genes (DEGs) were identified in the comparison between pSS and non-pSS groups, and 727 DEGs were observed between pSS-EGM and pSS-non-EGM. It is noteworthy that the expression levels of CXCL9 were higher in both pSS patients and pSS-EGM when compared to the control group. Taking into consideration the significance of the top 20 DEGs in relation to clinical parameters and the central hub genes, we ultimately chose CXCL9. In comparison to the non-pSS group, pSS patients exhibited notably greater expression of the CXCL9 gene in the MSG, as well as higher levels of CXCL9 protein in their plasma (p < 0.001). Furthermore, the expression of the CXCL9 gene and levels of CXCL9 protein were notably higher in pSS patients accompanied by EGM and those with SSA antibodies. Additionally, a correlation was found between the expression of the CXCL9 gene and the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI), as well as with immunoglobulin G (IgG) levels and erythrocyte sedimentation rate (ESR). Meanwhile, the protein levels of CXCL9 were found to be correlated with IgG levels and ESSDAI. CONCLUSION: CXCL9 proves to be a valuable biomarker in pSS, specifically due to its strong ability to differentiate between pSS patients with EGM and those without EGM. There is a significant correlation between CXCL9 and various clinical parameters both at the gene and protein level. Therefore, CXCL9 could be a potential target for future treatment of pSS.

A noninvasive multianalytical approach establishment for risk assessment and gastric cancer screening.

Effective screening and early detection are critical to improve the prognosis of gastric cancer (GC). Our study aims to explore noninvasive multianalytical biomarkers and construct integrative models for preliminary risk assessment and GC detection. Whole genomewide methylation marker discovery was conducted with CpG tandems target amplification (CTTA) in cfDNA from large asymptomatic screening participants in a high-risk area of GC. The methylation and mutation candidates were validated simultaneously using one plasma from patients at various gastric lesion stages by multiplex profiling with Mutation Capsule Plus (MCP). Helicobacter pylori specific antibodies were detected with a recomLine assay. Integrated models were constructed and validated by the combination of multianalytical biomarkers. A total of 146 and 120 novel methylation markers were found in CpG islands and promoter regions across the genome with CTTA. The methylation markers together with the candidate mutations were validated with MCP and used to establish a 133-methylation-marker panel for risk assessment of suspicious precancerous lesions and GC cases and a 49-methylation-marker panel as well as a 144-amplicon-mutation panel for GC detection. An integrated model comprising both methylation and specific antibody panels performed better for risk assessment than a traditional model (AUC, 0.83 and 0.63, P < .001). A second model for GC detection integrating methylation and mutation panels also outperformed the traditional model (AUC, 0.82 and 0.68, P = .005). Our study established methylation, mutation and H. pylori-specific antibody panels and constructed two integrated models for risk assessment and GC screening. Our findings provide new insights for a more precise GC screening strategy in the future.

Hollow Starlike Ag/CoMo-LDH Heterojunction with a Tunable d-Band Center for Boosting Oxygen Evolution Reaction Electrocatalysis.

It is a challenging task to utilize efficient electrocatalytic metal hydroxide-based materials for the oxygen evolution reaction (OER) in order to produce clean hydrogen energy through water splitting, primarily due to the restricted availability of active sites and the undesirably high adsorption energies of oxygenated species. To address these challenges simultaneously, we intentionally engineer a hollow star-shaped Ag/CoMo-LDH heterostructure as a highly efficient electrocatalytic system. This design incorporates a considerable number of heterointerfaces between evenly dispersed Ag nanoparticles and CoMo-LDH nanosheets. The heterojunction materials have been prepared using self-assembly, in situ transformation, and spontaneous redox processes. The nanosheet-integrated hollow architecture can prevent active entities from agglomeration and facilitate mass transportation, enabling the constant exposure of active sites. Specifically, the powerful electronic interaction within the heterojunction can successfully regulate the Co3+/Co2+ ratio and the d-band center, resulting in rational optimization of the adsorption and desorption of the intermediates on the site. Benefiting from its well-defined multifunctional structures, the Ag0.4/CoMo-LDH with optimal Ag loading exhibits impressive OER activity, the overpotential being 290 mV to reach a 10 mA cm-2 current density. The present study sheds some new insights into the electron structure modulation of hollow heterostructures toward rationally designing electrocatalytic materials for the OER.

Letter to Editor Regarding "Methylene Blue Staining and Ultrasonic Debridement: A Superior Therapeutic Strategy for Pressure Ulcer Debridement".

The treatment of pressure ulcer is of an extreme clinical and social concern. Effective and thorough debridement lays the foundation for favorable wound healing. Recently, a case report confirmed the efficacy of a combined application of methylene blue staining and ultrasonic debridement for pressure ulcer debridement. A 91-year-old male who suffered from severe pressure ulcers for over 6 years eventually obtained a favorable restoration after receiving surgical debridement optimized with methylene blue staining and ultrasonic debridement. We write to learn more about the details of the case. In this letter, we raised some questions involving the identification capability of methylene blue staining among different tissues, the application of methylene blue staining for various wounds, the arrangement of the debridement liquid, and the management strategy after wound closure. We thank the authors for creating a successful paradigm and hope the discussion can make sense for guiding subsequent clinical practice.

The Musa troglodytarum L. genome provides insights into the mechanism of non-climacteric behaviour and enrichment of carotenoids.

BACKGROUND: Karat (Musa troglodytarum L.) is an autotriploid Fe'i banana of the Australimusa section. Karat was domesticated independently in the Pacific region, and karat fruit are characterized by a pink sap, a deep yellow-orange flesh colour, and an abundance of ß-carotene. Karat fruit showed non-climacteric behaviour, with an approximately 215-day bunch filling time. These features make karat a valuable genetic resource for studying the mechanisms underlying fruit development and ripening and carotenoid biosynthesis. RESULTS: Here, we report the genome of M. troglodytarum, which has a total length of 603 Mb and contains 37,577 predicted protein-coding genes. After divergence from the most recent common ancestors, M. troglodytarum (T genome) has experienced fusion of ancestral chromosomes 8 and 9 and multiple translocations and inversions, unlike the high synteny with few rearrangements found among M. schizocarpa (S genome), M. acuminata (A genome) and M. balbisiana (B genome). Genome microsynteny analysis showed that the triplication of MtSSUIIs due to chromosome rearrangement may lead to the accumulation of carotenoids and ABA in the fruit. The expression of duplicated MtCCD4s is repressed during ripening, leading to the accumulation of α-carotene, ß-carotene and phytoene. Due to a long terminal repeat (LTR)-like fragment insertion upstream of MtERF11, karat cannot produce large amounts of ethylene but can produce ABA during ripening. These lead to non-climacteric behaviour and prolonged shelf-life, which contributes to an enrichment of carotenoids and riboflavin. CONCLUSIONS: The high-quality genome of M. troglodytarum revealed the genomic basis of non-climacteric behaviour and enrichment of carotenoids, riboflavin, flavonoids and free galactose and provides valuable resources for further research on banana domestication and breeding and the improvement of nutritional and bioactive qualities.

Rational Design of Chiral Tridentate Ligands: Bifunctional Cobalt(II) Complex/Hydrogen Bond for Enantioselective Michael Reactions.

Bifunctional chiral tridentate bis(pyrroloimidazolone)pyridine (PyBPI) ligands have been designed, synthesized, and applied in an asymmetric Michael addition. With a 0.05 mol % PyBPI-Co(II) complex, ß,γ-unsaturated α-keto esters reacted with 4-hydroxycoumarin to give the adducts in 93-99% yields and 90-97% ee. Experiments and DFT calculations supported the dual activation manner, in which the tridentate ligand coordinated with Co(II) to activate the keto ester, and the hydroxyl and carbonyl groups in PyBPI interacted with 4-hydroxycoumarin via two different H bonds.

Beetleane A and Epicoane A: Two Carbon Skeletons Produced by Epicoccum nigrum.

Two novel natural products, beetleane A (1) and epicoane A (2), were obtained from the metabolites of an endophytic Epicoccum nigrum. Compound 1 has a unique beetlelike structure that is constructed by the fusion and further fold of an unusual [5.5.5.6]trioxafenestrane with a cycloheptane ring. Compound 2 possesses a compact cagelike structure with a unique 6/5/5/5/6/6/5 heptacyclic ring system. Both 1 and 2 showed strong antiliver fibrosis activity in vitro.

Mapping Intellectual Structures and Research Hotspots of Triple Negative Breast Cancer: A Bibliometric Analysis.

BACKGROUND: Triple negative breast cancer (TNBC) is a highly heterogeneous breast cancer subtype with a poor prognosis due to its extremely aggressive nature and lack of effective treatment options. This study aims to summarize the current hotspots of TNBC research and evaluate the TNBC research trends, both qualitatively and quantitatively. METHODS: Scientific publications of TNBC-related studies from January 1, 2010 to October 17, 2020 were obtained from the Web of Science database. The BICOMB software was used to obtain the high-frequency keywords layout. The gCLUTO was used to produce a biclustering analysis on the binary matrix of word-paper. The co-occurrence and collaboration analysis between authors, countries, institutions, and keywords were performed by VOSviewer software. Keyword burst detection was performed by CiteSpace. RESULTS: A total of 12,429 articles related to TNBC were identified. During 2010-2020, the most productive country/region and institution in TNBC field was the USA and The University of Texas MD Anderson Cancer Center, respectively. Cancer Research, Journal of Clinical Oncology, and Annals of Oncology were the first three periodicals with maximum publications in TNBC research. Eight research hotspots of TNBC were identified by co-word analysis. In the core hotspots, research on neoadjuvant chemotherapy, paclitaxel therapy, and molecular typing of TNBC is relatively mature. Research on immunotherapy and PARP inhibitor for TNBC is not yet mature but is the current focus of this field. Burst detection of keywords showed that studies on TNBC proteins and receptors, immunotherapy, target, and tumor cell migration showed bursts in recent three years. CONCLUSION: The current study revealed that TNBC studies are growing. Attention should be paid to the latest hotspots, such as immunotherapy, PARP inhibitors, target, and TNBC proteins and receptors.

Two novel diterpenes from the stems and leaves of tropical seagrass Enhalus acoroides in the South China sea.

Two novel diterpenes Enhoidin A (1) and Enhoidin B (2) featuring an unusual gibberellane skeleton were isolated from the stems and leaves of Enhalus acoroides. Their structures were elucidated on the basis of spectroscopic analysis including 1D and 2D NMR techniques and HR-ESI-MS. This is the first time that this type of lactone ring between C-18 and C-20 has been found among gibberellanes from the tropical seagrasses. Evaluation of the all compounds for cytotoxicity against four human cancer cell lines (MCF-7, HCT-116, HepG-2 and HeLa), and showed moderate cytotoxic activities.

The Characteristics and Mortality of Osteoporosis, Osteomyelitis, or Rheumatoid Arthritis in the Diabetes Population: A Retrospective Study.

BACKGROUND: Patients with diabetes mellitus are prone to develop osteoporosis, osteomyelitis, or rheumatoid arthritis (RA). Furthermore, the presence of these complications in those with diabetes may lead to higher mortality. The aim of our study was to assess characteristics and mortality of osteoporosis, osteomyelitis, or rheumatoid arthritis in individuals with diabetes. METHODS: We analyzed osteoporosis, osteomyelitis, and RA deaths associated with diabetes from 1999-2017 using the CDC WONDER system (CDC WONDER; https://wonder.cdc.gov). We used ICD-10 codes to categorize the underlying and contributing causes of death. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMR) per 1,000,000 person-years were calculated. RESULTS: The AAMR for osteoporosis in the population with diabetes was significantly higher in females (AAMR: 4.17, 95% CI: 4.10-4.24) than in males (AAMR: 1.12, 95% CI: 1.07-1.16). Deaths due to osteoporosis increased gradually from 1999, peaked in 2003 (AAMR: 3.78, 95% CI: 3.55-4.00), and reached a nadir in 2016 (AAMR: 2.32, 95% CI: 2.15-2.48). The AAMR for RA associated with diabetes was slightly higher in females (AAMR: 4.04, 95% CI: 3.98-4.11) than in males (AAMR: 2.45, 95% CI: 2.39-2.51). The mortality rate due to RA increased slightly from 1999 (AAMR: 3.18, 95% CI: 2.97-3.39) to 2017 (AAMR: 3.20, 95% CI: 3.02-3.38). The AAMR for osteomyelitis associated with diabetes was higher in males (AAMR: 4.36, 95% CI: 4.28-4.44) than in females (AAMR: 2.31, 95% CI: 2.26-2.36). From 1999 to 2017, the AAMR from osteomyelitis in this population was 2.63 (95% CI: 2.44-2.82) per 1,000,000 person-years in 1999 and 4.25 (95% CI: 4.05-4.46) per 1,000,000 person-years in 2017. CONCLUSIONS: We found an increase in the age-adjusted mortality rates of RA and osteomyelitis and a decrease of osteoporosis associated with diabetes from 1999 to 2017. We suggest that increased attention should therefore be given to these diseases in the population with diabetes, especially in efforts to develop preventative and treatment strategies.

Real-World Evidence in Prescription Medication Use Among U.S. Adults with Neck Pain.

INTRODUCTION: Neck pain is a common condition that leads to serious pain, disability, and increased healthcare costs worldwide. Pharmacotherapy is one of the most common strategies to reduce neck pain in patients. The aim of this study was to analyze the real-world pattern of drugs prescribed for patients with neck pain in the USA. METHODS: Data on individuals who reported current neck pain in the 2009-2010 US National Health and Nutrition Examination Survey (NHANES) and with a history of persistent pain for at least 6 weeks or 3 months were extracted from the NHANES database. Those included in the study were divided into three groups based on the duration of pain: the without neck pain group (Group A); subacute group (Group B) with a history of 6 weeks of neck pain; and the chronic neck pain group (Group C) with a history of 3 months of neck pain. The use and duration of medication prescribed for Group A, B, and C patients were compared. RESULTS: The analysis revealed that opioid use was significantly more prevalent in the subacute and chronic neck pain group than in the without neck pain group (Group A) (adjusted odds ratio [aOR] 4.20, 95% confidence interval [CI] 2.07-8.52 and aOR 7.00, 95% CI 4.32-11.33, respectively). The factors strongly associated with higher opioid use included older age, low education level, and low family income. In the chronic neck group, opioids, followed in decreasing order of frequency by acetaminophen and nonsteroidal anti-infammatory drugs, were the most common analgesics used in combination with other analgesics. CONCLUSION: Our analysis of the data shows that the long-term excessive use of opioids and the underutilization of other analgesics are two major issues in the treatment of neck pain in the USA. Possible improvements include improved education of patients by healthcare professionals on the use of opioids and more consideration given to non-pharmacotherapy options. Our results reveal the potential problem in pharmacotherapy choices for neck pain treatment and may help improve the current clinical practice in the USA and other countries.

Chromone and donepezil hybrids as new multipotent cholinesterase and monoamine oxidase inhibitors for the potential treatment of Alzheimer's disease.

A series of chromone and donepezil hybrids were designed, synthesized, and evaluated as multipotent cholinesterase (ChE) and monoamine oxidase (MAO) inhibitors for the potential therapy of Alzheimer's disease (AD). In vitro studies showed that the great majority of these compounds exhibited potent inhibitory activity toward BuChE and AChE and clearly selective inhibition for hMAO-B. In particular, compound 5c presented the most balanced potential for ChE inhibition (BuChE: IC50 = 5.24 µM; AChE: IC50 = 0.37 µM) and hMAO-B selectivity (IC50 = 0.272 µM, SI = 247). Molecular modeling and kinetic studies suggested that 5c was a mixed-type inhibitor, binding simultaneously to peripheral and active sites of AChE. It was also a competitive inhibitor, which occupied the substrate and entrance cavities of MAO-B. Moreover, compound 5c could penetrate the blood-brain barrier (BBB) and showed low toxicity to rat pheochromocytoma (PC12) cells. Altogether, these results indicated that compound 5c might be a hopeful multitarget drug candidate with possible impact on Alzheimer's disease therapy.

Usnic acid derivatives as tau-aggregation and neuroinflammation inhibitors.

Accumulation of tau protein aggregation plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). Uncontrollable neuroinflammation and tau pathology form a vicious circle that further aggravates AD progression. Herein, we reported the synthesis of usnic acid derivatives and evaluation of their inhibitory activities against tau-aggregation and neuroinflammation. The inhibitory activity of the derivatives against the self-fibrillation of the hexapeptide AcPHF6 was initially screened by ThT fluorescence assay. Using circular dichroism and transmission electron microscopy, compound 30 showed the most potent inhibitory activity against AcPHF6 self-fibrillation. Compound 30 was further confirmed to inhibit the aggregation of full-length 2N4R tau protein by a heparin-induced mechanism. In addition, we investigated the anti-inflammatory activity of compound 30, and showed that compared with sodium usnate, it reduced NO release in LPS-stimulated mouse microglia BV2 cells. More importantly, 30 showed significant protective effects against okadaic acid-induced memory impairment in rats. Thus, 30 was a novel tau-aggregation and neuroinflammation inhibitor that represented a potential therapeutic candidate for AD.

Author Correction: De novo assembly of the Platycladus orientalis (L.) Franco transcriptome provides insight into the development and pollination mechanism of female cone based on RNA-Seq data.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Hyperberins A and B, Type B Polycyclic Polyprenylated Acylphloroglucinols with Bicyclo[5.3.1]hendecane Core from Hypericum beanii.

The first examples of type B polycyclic polyprenylated acylphloroglucinols with a bicyclo[5.3.1]hendecane core, hyperberins A (1) and B (2), were isolated from Hypericum beanii, together with three biosynthetic congeners. Their structures were established by a combination of NMR, electric circular dichroism (ECD), and X-ray diffraction analyses. These isolates indicated divergent cationic cyclization as key steps in the biosynthesis of PPAPs with diverse architectures. Compounds 1 and 2 were moderately cytotoxic and exhibited significant anti-inflammatory activities.

Treating aplasia cutis congenita in a newborn with the combination of ionic silver dressing and moist exposed burn ointment: A case report.

BACKGROUND: Aplasia cutis congenita (ACC) in newborns is a condition in which congenital defects or hypoplasia is present in part of the epidermis, dermis and even subcutaneous tissue (including muscle and bones). First reported by Cordon in 1767, ACC is a rare disease with a low incidence of 1/100000 to 3/10000. Currently, there are 500 cases reported worldwide. ACC can be accompanied by other malformations. The onset mechanism of the disease remains unknown but is thought to be correlated to factors such as genetics, narrow uterus, foetal skin and amniotic membrane adhesion, use of teratogenic drugs in early pregnancy and viral infection. CASE SUMMARY: In August 2018, we treated a newborn with ACC on the left lower limbs using a combination of ionic silver dressing and moist exposed burn ointment (MEBO) and achieved a satisfactory treatment outcome. The skin defects were observed on the external genitals and on areas from the left foot to 3/4 of the upper left side. Subcutaneous tissue and blood vessels were observed in the regions with skin defects. The following treatments were provided. First, the wound was rinsed with 0.9% sodium chloride solution followed by disinfection with povidone-iodine twice. And then MEBO was applied to the wound at a thickness of approximately 1 mm. After applying ionic silver dressing, the wound was covered with sterile gauze. The wound dressing was replaced every 2-3 d. At the 4-mo follow-up, the treatment outcome was satisfactory. There was minimal scar tissue formation, and limb function was not impaired. CONCLUSION: The combination of ionic silver dressing and MEBO to ACC is helpful.

De novo assembly of the Platycladus orientalis (L.) Franco transcriptome provides insight into the development and pollination mechanism of female cone based on RNA-Seq data.

For seed-bearing plants, the basis of seed and fruit formation is pollination. The normal progression of pollination is through advances in continuous signal exchange and material transfer, which occur mainly in female reproductive organs; thus, the molecular mechanism of development in female reproductive organs is vital for understanding the principle of pollination. However, molecular biology studies on the development of female cones related to pollination are rare and unclear in gymnosperms, especially in Cupressaceae. In this study, Platycladus orientalis, a monotypic genus within Cupressaceae, was chosen to examine female cone transcriptomes at pre-pollination and pollination stages by Illumina paired-end sequencing technology to de novo sequence six libraries with 3 biological replicates. These libraries were used to construct a P. orientalis transcriptome database containing 71,669 unigenes (4,963 upregulated unigenes and 11,747 downregulated unigenes at the pollination stage) for subsequent analysis. Based on the annotations and expression levels, the functions of differentially expressed unigenes and enriched pathways between the developmental processes of female cones were analysed to detail the preliminary development and pollination mechanism of the female cone. Targeted investigations were specifically performed to determine the elementary mechanism of secretion and functioning of the pollination drop, a vital ovule secretion at the pollination stage. Ultimately, the expression of 15 unigenes selected between two stages were further assessed and confirmed using qRT-PCR, which demonstrated reliable data and significant differences in the expression profiles of key genes. As one of the largest available transcriptomic resources of this species, the database is constructed to prospectively adapt to the physiological and genomic data of woody plants. This work provided the first transcriptome profile of P. orientalis female cones at different developmental stages, and will promote the illumination of the pollination mechanism of P. orientalis, and will serve as the basis for in-depth genomic study in the Cupressaceae family. This initiative will arouse the interest and attention of scholars and pave the way for future studies.