Antimicrobial peptide-producing dermal preadipocytes defend against Candida albicans skin infection via the FGFR-MEK-ERK pathway.

Dermal fibroblasts (dFBs) defend against deep bacterial skin infections by differentiating into preadipocytes (pAds) that produce the antimicrobial peptide cathelicidin; this differentiation is known as the dermal reactive adipogenesis response. However, the role of dFBs in fungal infection remains unknown. Here, we found that cathelicidin-producing pAds were present in high numbers in skin lesions from patients with cutaneous Candida granulomas. Second, we showed that dermal Candida albicans (C. albicans) infection in mice robustly triggered the dermal reactive adipogenesis response and induced cathelicidin expression, and inhibition of adipogenesis with pharmacological inhibitors of peroxisome proliferator-activated receptor γ (PPARγ) impaired skin resistance to C. albicans. In vitro, C. albicans products induced cathelicidin expression in pAds, and differentiating pAds markedly suppressed the growth of C. albicans by producing cathelicidin. Finally, we showed that C. albicans induced an antimicrobial response in pAds through the FGFR-MEK-ERK pathway. Together, our data reveal a previously unknown role of dFBs in the defense against skin infection caused by C. albicans.

The transcription factor bZIP68 negatively regulates cold tolerance in maize.

Maize (Zea mays) originated in tropical areas and is thus susceptible to low temperatures, which pose a major threat to maize production. Our understanding of the molecular basis of cold tolerance in maize is limited. Here, we identified bZIP68, a basic leucine zipper (bZIP) transcription factor, as a negative regulator of cold tolerance in maize. Transcriptome analysis revealed that bZIP68 represses the cold-induced expression of DREB1 transcription factor genes. The stability and transcriptional activity of bZIP68 are controlled by its phosphorylation at the conserved Ser250 residue under cold stress. Furthermore, we demonstrated that the bZIP68 locus was a target of selection during early domestication. A 358-bp insertion/deletion (Indel-972) polymorphism in the bZIP68 promoter has a significant effect on the differential expression of bZIP68 between maize and its wild ancestor teosinte. This study thus uncovers an evolutionary cis-regulatory variant that could be used to improve cold tolerance in maize.

Off-target RNA mutation induced by DNA base editing and its elimination by mutagenesis.

Recently developed DNA base editing methods enable the direct generation of desired point mutations in genomic DNA without generating any double-strand breaks1-3, but the issue of off-target edits has limited the application of these methods. Although several previous studies have evaluated off-target mutations in genomic DNA4-8, it is now clear that the deaminases that are integral to commonly used DNA base editors often bind to RNA9-13. For example, the cytosine deaminase APOBEC1-which is used in cytosine base editors (CBEs)-targets both DNA and RNA12, and the adenine deaminase TadA-which is used in adenine base editors (ABEs)-induces site-specific inosine formation on RNA9,11. However, any potential RNA mutations caused by DNA base editors have not been evaluated. Adeno-associated viruses are the most common delivery system for gene therapies that involve DNA editing; these viruses can sustain long-term gene expression in vivo, so the extent of potential RNA mutations induced by DNA base editors is of great concern14-16. Here we quantitatively evaluated RNA single nucleotide variations (SNVs) that were induced by CBEs or ABEs. Both the cytosine base editor BE3 and the adenine base editor ABE7.10 generated tens of thousands of off-target RNA SNVs. Subsequently, by engineering deaminases, we found that three CBE variants and one ABE variant showed a reduction in off-target RNA SNVs to the baseline while maintaining efficient DNA on-target activity. This study reveals a previously overlooked aspect of off-target effects in DNA editing and also demonstrates that such effects can be eliminated by engineering deaminases.

Multi-omics analysis revealed that the protein kinase MoKin1 affected the cellular response to endoplasmic reticulum stress in the rice blast fungus, Magnaporthe oryzae.

BACKGROUND: Previous studies have shown that protein kinase MoKin1 played an important role in the growth, conidiation, germination and pathogenicity in rice blast fungus, Magnaporthe oryzae. ΔMokin1 mutant showed significant phenotypic defects and significantly reduced pathogenicity. However, the internal mechanism of how MoKin1 affected the development of physiology and biochemistry remained unclear in M. oryzae. RESULT: This study adopted a multi-omics approach to comprehensively analyze MoKin1 function, and the results showed that MoKin1 affected the cellular response to endoplasmic reticulum stress (ER stress). Proteomic analysis revealed that the downregulated proteins in ΔMokin1 mutant were enriched mainly in the response to ER stress triggered by the unfolded protein. Loss of MoKin1 prevented the ER stress signal from reaching the nucleus. Therefore, the phosphorylation of various proteins regulating the transcription of ER stress-related genes and mRNA translation was significantly downregulated. The insensitivity to ER stress led to metabolic disorders, resulting in a significant shortage of carbohydrates and a low energy supply, which also resulted in severe phenotypic defects in ΔMokin1 mutant. Analysis of MoKin1-interacting proteins indicated that MoKin1 really took participate in the response to ER stress. CONCLUSION: Our results showed the important role of protein kinase MoKin1 in regulating cellular response to ER stress, providing a new research direction to reveal the mechanism of MoKin1 affecting pathogenic formation, and to provide theoretical support for the new biological target sites searching and bio-pesticides developing.

Genetic variation in the aquaporin TONOPLAST INTRINSIC PROTEIN 4;3 modulates maize cold tolerance.

Cold stress is a major abiotic stress that threatens maize (Zea mays L.) production worldwide. Understanding the molecular mechanisms underlying cold tolerance is crucial for breeding resilient maize varieties. Tonoplast intrinsic proteins (TIPs) are a subfamily of aquaporins in plants. Here, we report that TIP family proteins are involved in maize cold tolerance. The expression of most TIP genes was responsive to cold stress. Overexpressing TIP2;1, TIP3;2 or TIP4;3 reduced the cold tolerance of maize seedlings, while loss-of-function mutants of TIP4;3 exhibited enhanced cold tolerance. Candidate gene-based association analysis revealed that a 328-bp transposon insertion in the promoter region of TIP4;3 was strongly associated with maize cold tolerance. This transposon insertion conferred cold tolerance by repressing TIP4;3 expression through increased methylation of its promoter region. Moreover, TIP4;3 was found to suppress stomatal closure and facilitate reactive oxygen species (ROS) accumulation under cold stress, thereby inhibiting the expression of cold-responsive genes, including DEHYDRATION-RESPONSIVE ELEMENT BINDING FACTOR 1 (DREB1) genes and a subset of peroxidase genes, ultimately attenuating maize cold tolerance. This study thus elucidates the mechanism underlying TIP-mediated cold tolerance and identifies a favourable TIP4;3 allele as a potential genetic resource for breeding cold-tolerant maize varieties.

Outcomes of endovascular therapy for Stanford type B aortic dissection in patients with sleep apnea syndrome.

OBJECTIVE: This study aimed to determine the influences of varying severity of sleep apnea syndrome (SAS) on the outcomes after thoracic endovascular aorta repair (TEVAR) in patients with Stanford type B aortic dissection (TBAD). METHODS: This observational study focused on individuals with TBAD plus SAS who received TEVAR between January 2018 and December 2022. Patients were divided into groups according to the results of the portable sleep-breathing monitoring systems: mild SAS (MSAS) and moderate-to-severe SAS (MSSAS). Clinical profiles were collected and analyzed. RESULTS: A total of 121 cases with TBAD plus SAS who underwent TEVAR were enrolled in this study. Two groups were formed by stratifying these cases: MSAS (74 cases) and MSSAS (47 cases). The MSSAS cases were found to be older relative to MSAS cases (51.7 ± 8.3 years vs 57.1 ± 12.8 years; P = .012) and had a higher body mass index (BMI; 25.7 ± 2.3 kg/m2vs 27.0 ± 2.3 kg/m2; P = .038). The investigation did not find any appreciable differences between the MSAS and MSSAS groups in terms of complications (endoleak, P = .403; stent-induced new entry, P >.999; and stent displacement: P >.999). However, the MSSAS group exhibited a significantly higher overall mortality rate compared with the MSAS group (log-rank P = .027). The tendency continued when examining cases with Marfan syndrome combined with MSSAS, where the overall mortality rate was significantly greater compared with Marfan syndrome cases with MSAS (log-rank P = .037). The absence of a significant difference was noteworthy in the freedom from reintervention between the MSAS and MSSAS groups (log-rank P = .278). The overall mortality rate was significantly higher in MSSAS group even after adjusting for varying potential confounders in the multivariate cox regression analysis (hazard ratio [HR], 1.875; 95% confidence interval [CI], 1.238-2.586; P = .012). A markedly higher rate of distal stent dilation in the MSSAS group was also observed compared with the MSAS group (HR, 2.5 mm/year [95% CI, 2-3 mm/year] vs HR, 4 mm/year [95% CI, 2.0-5.5 mm/year]; P = .029). CONCLUSIONS: MSSAS is associated with a significantly higher risk of overall mortality and dilation rate of the distal stent after TEVAR for TBAD patients. Hence, aggressive efforts to reverse the severity of SAS in time in these individuals seem to be necessary.

Targeting lysyl oxidase like 2 attenuates OVA-induced airway remodeling partly via the AKT signaling pathway.

BACKGROUND: Airway epithelium is an important component of airway structure and the initiator of airway remodeling in asthma. The changes of extracellular matrix (ECM), such as collagen deposition and structural disturbance, are typical pathological features of airway remodeling. Thus, identifying key mediators that derived from airway epithelium and capable of modulating ECM may provide valuable insights for targeted therapy of asthma. METHODS: The datasets from Gene Expression Omnibus database were analyzed to screen differentially expressed genes in airway epithelium of asthma. We collected bronchoscopic biopsies and serum samples from asthmatic and healthy subjects to assess lysyl oxidase like 2 (LOXL2) expression. RNA sequencing and various experiments were performed to determine the influences of LOXL2 knockdown in ovalbumin (OVA)-induced mouse models. The roles and mechanisms of LOXL2 in bronchial epithelial cells were explored using LOXL2 small interfering RNA, overexpression plasmid and AKT inhibitor. RESULTS: Both bioinformatics analysis and further experiments revealed that LOXL2 is highly expressed in airway epithelium of asthmatics. In vivo, LOXL2 knockdown significantly inhibited OVA-induced ECM deposition and epithelial-mesenchymal transition (EMT) in mice. In vitro, the transfection experiments on 16HBE cells demonstrated that LOXL2 overexpression increases the expression of N-cadherin and fibronectin and reduces the expression of E-cadherin. Conversely, after silencing LOXL2, the expression of E-cadherin is up-regulated. In addition, the remodeling and EMT process that induced by transforming growth factor-ß1 could be enhanced and weakened after LOXL2 overexpression and silencing in 16HBE cells. Combining the RNA sequencing of mouse lung tissues and experiments in vitro, LOXL2 was involved in the regulation of AKT signaling pathway. Moreover, the treatment with AKT inhibitor in vitro partially alleviated the consequences associated with LOXL2 overexpression. CONCLUSIONS: Taken together, the results demonstrated that epithelial LOXL2 plays a role in asthmatic airway remodeling partly via the AKT signaling pathway and highlighted the potential of LOXL2 as a therapeutic target for airway remodeling in asthma.

Necroptosis plays a role in TL1A-induced airway inflammation and barrier damage in asthma.

BACKGROUND: Airway epithelial cell (AEC) necroptosis contributes to airway allergic inflammation and asthma exacerbation. Targeting the tumor necrosis factor-like ligand 1 A (TL1A)/death receptor 3 (DR3) axis has a therapeutic effect on asthmatic airway inflammation. The role of TL1A in mediating necroptosis of AECs challenged with ovalbumin (OVA) and its contribution to airway inflammation remains unclear. METHODS: We evaluated the expression of the receptor-interacting serine/threonine-protein kinase 3(RIPK3) and the mixed lineage kinase domain-like protein (MLKL) in human serum and lung, and histologically verified the level of MLKL phosphorylation in lung tissue from asthmatics and OVA-induced mice. Next, using MLKL knockout mice and the RIPK3 inhibitor GSK872, we investigated the effects of TL1A on airway inflammation and airway barrier function through the activation of necroptosis in experimental asthma. RESULTS: High expression of necroptosis marker proteins was observed in the serum of asthmatics, and necroptosis was activated in the airway epithelium of both asthmatics and OVA-induced mice. Blocking necroptosis through MLKL knockout or RIPK3 inhibition effectively attenuated parabronchial inflammation, mucus hypersecretion, and airway collagen fiber accumulation, while also suppressing type 2 inflammatory factors secretion. In addition, TL1A/ DR3 was shown to act as a death trigger for necroptosis in the absence of caspases by silencing or overexpressing TL1A in HBE cells. Furthermore, the recombinant TL1A protein was found to induce necroptosis in vivo, and knockout of MLKL partially reversed the pathological changes induced by TL1A. The necroptosis induced by TL1A disrupted the airway barrier function by decreasing the expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin, possibly through the activation of the NF-κB signaling pathway. CONCLUSIONS: TL1A-induced airway epithelial necroptosis plays a significant role in promoting airway inflammation and barrier dysfunction in asthma. Inhibition of the TL1A-induced necroptosis pathway could be a promising therapeutic strategy.

Utilizing Single-Branched Stent in Combination With Fenestration or Chimney for Endovascular Repair of Aortic Arch Lesions With Aberrant Subclavian Artery.

OBJECTIVE: The study was to figure out the feasibility, efficacy, and safety of a single-branched stent graft, namely Castor, in combination with fenestration or chimney in the context of aortic arch lesions presenting with aberrant subclavian artery (ASA) and/or Kommerell's diverticulum (KD). METHODS: All consecutive patients with aortic arch lesions and ASA and/or KD receiving Castor from June 2018 to June 2023 were investigated. RESULTS: Incorporating 18 patients, the study encompassed 11 cases with KD, 3 cases with dysphagia; 2 cases of right-sided aortic arch with left-sided aberrant left subclavian artery (ALSA), and 16 cases of left-sided aortic arch with right-sided aberrant right subclavian artery (ARSA). The mean operation time was 132±23 minutes. The mean measured proximal aortic diameter was 30.9±1.6 mm, and proximal diameter of Castor stent was 34 (32, 34.5) mm, with oversize of 9.1±1.6%; the mean measured branch diameter was 8.8±0.97 mm, and branch diameter of Castor stent was 10 (8, 10) mm, with oversize of 0.86±0.57 mm. Technical success rate was 100%, and no in-hospital mortality, no stroke, and no endoleak were identified. One (5.6%) case with spinal cord ischemia and one (5.6%) case with poor healing of operative site were identified. During the follow-up period, no aortic-related death or secondary intervention was recorded. The maximal aortic diameter was significantly reduced at the sixth postoperative month (padj=0.031); KD diameter was significantly reduced at the third (padj=0.001) and sixth (padj<0.001) postoperative month. CONCLUSION: Totally endovascular repair of aortic arch lesions with ASA and KD via Castor stent in combination with fenestration or chimney is feasible, effective, and safe, which can achieve an encouraging medium-term outcome and provide excellent remodeling at the lesions. CLINICAL IMPACT: Single branched stent in combination with fenestration or chimney achieved a sufficient proximal landing zone and provided an encouraging medium-term outcome in this retrospective review of 18 patients receiving endovascular treatment of pathological aortic arch with aberrant subclavian artery and/or Kommerell's diverticulum. The authors suggest this time-saving and efficient technique to establish systematic experience for the treatment in this kind of patients.

An Anatomic Classification Scheme for Surgical Planning of Renal Artery Aneurysms.

PURPOSE: Renal artery aneurysm (RAA) is a rare disease. This study proposed and evaluated a new classification for RAA to assist in surgical decision-making. MATERIALS AND METHODS: Single-center data of 105 patients with RAAs from the vascular department of vascular surgery were collected retrospectively. A new classification scheme was proposed. Type I aneurysms arise from the main trunk, accessory branch, or first-order branches away from any bifurcation. Type II aneurysms arise from the first bifurcation with narrow necks (defined as dome-to-neck ratio >2) or from intralobular branches. Type III aneurysms with a wide neck arise from the first bifurcation and affect 2 or more branches that cannot be sacrificed without significant infarction of the kidney. RESULTS: There was 50 (47.62%) type I, 33 (31.43%) type II, and 22 (20.95%) type III aneurysms. The classification assigned endovascular repair as first-line treatment (for type I or II), while open techniques were conducted if anatomically suitable (for type III). A kappa level of 0.752 was achieved by the classification compared with a level of 0.579 from the classic Rundback classification. Technical primary success was achieved in 100% and 96.05%, and symptoms were completely resolved in 100% and 84.85%, while hypertension was relieved in 84.21% and 72.92% of patients receiving open surgery or endovascular repair, respectively. No significant difference was observed for perioperative or long-term complications among the 3 classification types. CONCLUSION: The new classification proved to be a convenient and effective method for facilitating choice of intervention for RAAs. CLINICAL IMPACT: This study proposed and evaluated a new classification scheme for renal artery aneurysms, which proved to be a convenient and effective method for facilitating surgical decision-making. Coil embolization was the first-line treatment if suitable, while aneurysm resection and reconstruction with vein graft were conducted for some complex lesions. The safety and efficacy of both open and endovascular methods were validated.

Treatment failure is a key factor in the development of Helicobacter pylori resistance.

BACKGROUND: Helicobacter pylori eradication failure influences its antibiotic resistance. AIMS: This study aimed to evaluate the effect of previous treatment failures on it, including the changes in the antibiotic resistance rates, minimal inhibitory concentration (MIC) distributions, and resistance patterns. MATERIALS AND METHODS: This single-center retrospective study included 860 primary isolates and 247 secondary isolates. Antibiotic susceptibility testing was performed for amoxicillin, metronidazole, clarithromycin, levofloxacin, furazolidone, tetracycline, and rifampicin. The demographic data and detailed regimens were collected. RESULTS: The primary resistance rates to amoxicillin, metronidazole, clarithromycin, levofloxacin, tetracycline, rifampin, and furazolidone were 5.93%, 83.84%, 28.82%, 26.28%, 0.35%, 1.16%, and 0%, while secondary were 25.10%, 92.31%, 79.76%, 63.16%, 1.06%, 3.19%, and 0%, respectively. The resistance rates to amoxicillin, metronidazole, clarithromycin, and levofloxacin increased significantly with the number of treatment failures accumulated, and showed a linear trend. The proportion of primary and secondary multidrug-resistant (MDR) isolates were 17.79% and 63.16%, respectively. The MIC values of amoxicillin, clarithromycin, and levofloxacin were elevated significantly with medication courses increased. CONCLUSION: The prevalence of amoxicillin, clarithromycin, levofloxacin, and metronidazole resistance would increase rapidly following first-line treatment failure, as well as the MIC values of them. Clinicians should pay great attention to the first-line treatment to cure H. pylori infection successfully.

Exposure levels and determinants of placental polybrominated diphenyl ethers in Chinese pregnant women.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are a group of widely used chemicals and humans are exposed to them in their daily life. PBDEs exposure during pregnancy may have adverse effects on pregnant women and their fetuses. Nevertheless, limited information is available on the levels and determinants of PBDEs exposure in Chinese pregnant women. METHODS: The internal exposure levels of eight PBDEs (BDE-28, 47, 99, 100, 153, 154, 183, and 209) in placental samples of 1280 pregnant women from Zunyi birth cohort were analyzed using gas chromatography tandem mass spectrometry. All PBDEs concentrations were lipid adjusted (ng/g lw). Determinants of exposure were assessed by multivariable logistic regression model. RESULTS: Eight PBDE homologues were quantifiable in more than 70% of the samples. The highest median concentrations were found for BDE-209 (2.78 ng/g lw), followed by BDE-153 (1.00 ng/g lw) and BDE-183 (0.93 ng/g lw). The level of ΣPBDEs ranged from 0.90 to 308.78 ng/g lw, with a median concentration of 10.02 ng/g lw. Multivariate logistic regression analysis showed that maternal age older than 30 years old (OR: 1.59; 95% CI: 1.14, 2.23), pre-pregnancy obesity (1.51; 1.08, 2.10), home renovation within 2 years (1.43; 1.08, 1.91), spending more time outdoors during pregnancy (0.70; 0.55, 0.89), high consumption of fish/seafood (1.46; 1.13, 1.90) and eggs (1.44; 1.04, 2.00), male infant sex (1.69; 1.18, 2.42) were associated with PBDEs exposure. CONCLUSION: The study population is generally exposed to PBDEs, of which BDE-209 is the dominant congener, indicating extensive application of products containing deca-BDE mixtures. Maternal age, pre-pregnancy BMI, home decoration, average outdoor time during pregnancy, fish, seafood, eggs consumption, and fetal sex were exposure-determinning factors. This study contributes to the knowledge on region-specific PBDEs contamination in pregnant women and related risk factors.

Recent advances in the treatment of acne using radiofrequency techniques.

Acne is a long-lasting inflammatory skin condition that impacts the sebaceous units of the hair follicles, affecting around 85-90% of the population. Due to the potential for permanent facial scarring and negative social consequences, as well as the limitations of conventional medications like drug resistance and difficulties following treatment plans, it's crucial to investigate non-pharmacological options for treating acne, among which radiofrequency(RF) shows distinct superiority. To assess the impact of RF in the management of acne vulgaris, we conducted a thorough examination of scientific literature (including clinical trials and scientific reviews) through electronic databases like MEDLINE and PubMed. Our analysis indicates that RF could be a viable substitute for acne treatment due to its notable effectiveness and minimal adverse effects.

Comparison of the 1064-nm picosecond laser with fractionated microlens array and 1565-nm non-ablative fractional laser for the treatment of enlarged pores: a randomized, split-face, controlled trial.

PURPOSE: This split-face randomized study compared the efficacy and safety between 1064-nm picosecond laser with fractionated microlens array (MLA) and 1565-nm nonablative fractional laser to treat enlarged pores. METHODS: Participants with enlarged facial pores were enrolled and underwent three consecutive sessions at 2-week intervals with either a 1064-nm picosecond laser with MLA or a 1565-nm nonablative fractional laser. Images were captured at each visit. Objective (pore number) and subjective assessments, including patient self-evaluations and quartile improvement scales, were used to evaluate the treatment efficacy. The pain levels and adverse effects were recorded at each subsequent visit. RESULTS: The participants were 3 men and 22 women with enlarged facial pores. At the initial and 2-month checkups after the last treatment, the pore numbers were significantly decreased bilaterally for both lasers. The respective quartile improvement scale scores for the 1064-nm picosecond and 1565-nm fractional lasers were 2.22 ± 1.06 and 2.14 ± 1.11, while those for patient self-assessment were 3.72 ± 0.74 and 3.68 ± 0.75. The pore number, quartile improvement scale score, and patients' self-assessments did not differ significantly between the two lasers. Treatment with the 1064-nm picosecond laser better reduced pain compared with the 1565-nm nonablative fractional laser (4.11 ± 1.33 vs. 4.83 ± 1.17). The occurrence of pigmentation did not differ significantly between the lasers. CONCLUSION: Both the 1064-nm picosecond laser with MLA and the 1565-nm nonablative fractional laser are viable options for treating enlarged pores, and showed comparable respective efficacies; however, the former was less likely to cause hyperpigmentation and was better tolerated.

First Report of Black Leaf Spot Caused by Epicoccum latusicollum on Chinese Yam in China.

Chinese yam (Dioscorea polystachya Turczaninow cv. Tiegun), which belongs to the family Dioscoreaceae, is widely cultivated throughout China due to its high economic and medicinal value. In June 2023, black leaf spots on Chinese yam (cv. Purple 1) were observed in Nanchang city (28.45° N, 115.49° E) of Jiangxi province, southeastern China. The incidence of the disease ranged between 70 and 85% of plants, and up to 30% of the leaves per plant were affected in the field over a 2-week period of study. Infected foliage displayed brown necrotic lesions, elliptical or irregular, with yellow halo at the edge of the lesion (0.5 to 3 cm diam.). To identify the causal agent, 32 symptomatic leaves of eight symptomatic plants were collected. Small pieces from the margin of necrotic leaf tissue (about 3 x 3 mm) were surface sterilized in 75% ethanol for 30 s followed in 0.1% HgCl2 for 1 min, and washed three times with ddH2O. Then, the pieces were transferred onto potato dextrose agar (PDA) plates and incubated at 26°C for 3 days with a 12-h light-dark cycle. From the 32 isolates, 21 exhibited similar morphology after hyphal tipping resulting in an isolation frequency of 65.6%. Colonies on PDA were initially white aerial hyphae but became grayish with age, and a reddish orange pigment on the underside. After 16 days of incubation, pycnidia were observed, which were dark, spherical or flat spherical, and 64.1 to 172.5 µm (n = 25) in diameter. Conidia were ellipsoidal, aseptate, hyaline, and 4.1 to 5.6 × 1.8 to 2.7 µm (n = 80). In addition, a blackish green discoloration was produced on malt extract agar (MEA) using the NaOH spot test. The isolates were tentatively identified as Epicoccum spp. based on morphological characteristics (Chen et al. 2017). Isolate AYZ-1 was randomly selected for identification and pathogenicity testing. Genomic DNA of the isolate (AYZ-1) was extracted and amplified by polymerase chain reaction (PCR) using ITS1/ITS4 for the internal transcribed spacer (ITS) region (White et al. 1990), Btub2Fd/Btub4Rd for the ß-tubulin (TUB) region (Woudenberg et al. 2009), LROR/LR7 for the large ribosomal RNA gene (LSU) region (Rehner and Samuels 1994), and RPB2-5F2/fRPB2-7cR for RNA polymerase II second largest subunit (RPB2) region (Liu et al. 1999), respectively. The concatenated sequences (GenBank Accession No. OR574165, OR567827, OR574166, OR567828, respectively) shared 99.8 to 100% identity with Epicoccum latusicollum (OP788080, MN329871, OR428532, and OL422485, respectively). A neighbor-joining phylogenetic tree was generated based on the concatenated sequences in MEGA7, placed isolate (AYZ-1) within E. latusicollum. To fulfill Koch's postulates, healthy leaflets from three one-year-old Chinese yam (cv. Purple 1) were used as inoculation materials, using isolate AYZ-1. Two sites of each leaf were wounded with a sterile needle and covered with a piece of cotton drenched with 200 µL spore suspension (106 conidia/mL) on the left sides, while sterilized water served as the control on the right sides of leaves. All inoculated leaves were covered with clear polyethylene bags for 24 h. Plants were grown outdoors at a daily average temperature of 26°C with relative humidity over 45%. After 7 days of incubation, the leaves showed the same symptoms as the original diseased leaves. The E. latusicollum isolate was re-isolated from diseased leaves and confirmed by morphology and sequencing analysis, fulfilling Koch's postulates. E. latusicollum has been previously reported to cause black root on yam in China's south-western province of Sichuan (Han et al. 2019). Meanwhile, leaf spot have been reported on many plants by this genus, such as tobacco (Guo et al. 2020) and banana (Liu et al. 2023). According to our knowledge, this is the first report of E. latusicollum causing black leaf spot on Chinese yam in China. This finding will provide an important reference for understanding the biology of E. latusicollum and the distribution of the disease, but more research is needed to determine if management is warranted.

26SCS-Loaded SilMA/Col Composite Sponge with Well-Arranged Layers Promotes Angiogenesis-Based Diabetic Wound Repair by Mediating Macrophage Inflammatory Response.

Diabetic wound healing is a significant clinical challenge because abnormal immune cells in the wound cause chronic inflammation and impair tissue regeneration. Therefore, regulating the behavior and function of macrophages may be conducive to improving treatment outcomes in diabetic wounds. Herein, sulfated chitosan (26SCS)-containing composite sponges (26SCS-SilMA/Col-330) with well-arranged layers and high porosity were constructed based on collagen and silk fibroin, aiming to induce an appropriate inflammatory response and promote angiogenesis. The results indicated that the ordered topological structure of composite sponges could trigger the pro-inflammatory response of Mφs in the early stage, and rapid release of 26SCS in the early and middle stages (within the concentration range of 1-3 mg/mL) induced a positive inflammatory response; initiated the pro-inflammatory reaction of Mφs within 3 days; shifted M1 Mφs to the M2 phenotype within 3-7 days; and significantly up-regulated the expression of two typical angiogenic growth factors, namely VEGF and PDGF-BB, on day 7, leading to rapid HUVEC migration and angiogenesis. In vivo data also demonstrated that on the 14th day after surgery, the 26SCS-SilMA/Col-330-implanted areas exhibited less inflammation, faster re-epithelialization, more abundant collagen deposition and a greater number of blood vessels in the skin tissue. The composite sponges with higher 26SCS contents (the (5.0) 26SCS-SilMA/Col-330 and the (7.5) 26SCS-SilMA/Col-330) could better orchestrate the phenotype and function of Mφs and facilitate wound healing. These findings highlight that the 26SCS-SilMA/Col-330 sponges developed in this work might have great potential as a novel dressing for the treatment of diabetic wounds.

Repeat-Enhancing Featured Ion-Guided Stoichiometry for Identification and Quantification of Direct Infusion Proteome.

The direct infusion-shotgun proteome analysis (DI-SPA) alongside data-independent acquisition mass spectrometry achieved fast proteome identification and quantification without chromatographic separation. However, robust peptide identification and quantification (label and label-free) for the DI-SPA data is still insufficient. We find that in the absence of chromatography, the identification of DI-SPA can be boosted by extending acquisition cycles repeatedly and maximizing the utilization of the featured repetition characteristics, combined with the machine learning-based automatic peptide scoring strategy. Here, we present the repeat-enhancing featured ion-guided stoichiometry (RE-FIGS), a complete and compact solution to (repeated) DI-SPA data. Using our strategy, the peptide identification can be improved above 30% with high reproducibility (70.0%). Notably, the label-free quantification of repeated DI-SPA can be successfully obtained with high accuracy (mean median error, 0.108) and high reproducibility (median error, 0.001). We believe our RE-FIGS method could boost the broad application of the (repeated) DI-SPA method and offer a new choice for proteomic analysis.

Plasma TNFRSF11B as a New Predictive Inflammatory Marker of Sepsis-ARDS with Endothelial Dysfunction.

Inflammation plays an important role in the development of sepsis-acute respiratory distress syndrome (ARDS). Olink inflammation-related biomarker panels were used to analyze the levels of 92 inflammation-related proteins in plasma with sepsis-ARDS (n = 25) and healthy subjects (n = 25). There were significant differences in 64 inflammatory factors, including TNFRSF11B in sepsis-ARDS, which was significantly higher than that in controls. Functional analysis showed that TNFRSF11B was closely focused on signal transduction, immune response, and inflammatory response. The TNFRSF11B level in sepsis-ARDS plasma, LPS-induced mice, and LPS-stimulated HUVECs significantly increased. The highest plasma concentration of TNFRSF11B in patients with sepsis-ARDS was 10-20 ng/mL, and 10 ng/mL was selected to stimulate HUVECs. Western blot results demonstrated that the levels of syndecan-1, claudin-5, VE-cadherin, occludin, aquaporin-1, and caveolin-1 in TNFRSF11B-stimulated HUVECs decreased, whereas that of connexin-43 increased in TNFRSF11B-stimulated HUVECs. To the best of the authors' knowledge, this study was the first to reveal elevated TNFRSF11B in sepsis-ARDS associated with vascular endothelial dysfunction. In summary, TNFRSF11B may be a new potential predictive and diagnostic biomarker for vascular endothelium damage in sepsis-ARDS.

Controllable C-H Alkylation of Polyethers via Iron Photocatalysis.

The efficient conversion of a C-H bond in the polyether chain to other functional groups provides great opportunities for development of novel applications in many research fields. However, this field is quite underdeveloped due to the key challenge on controlling the selectivity of the C-H bond functionalization over the chain cleavage. In this work, we report a controllable C-H bond alkylation of polyethers under mild conditions via photoinduced iron catalysis. The level of functionalization could be controlled by using different amounts of alkenes and various reaction times, while the molecular weight distributions were maintained narrow. A broad scope of electron-deficient alkenes containing nitrile, ester, epoxide, terminal alkynyl, 2,5-dioxotetrafuranyl, and 2,5-dioxopyrrolidinyl groups could be utilized to functionalize the different polyethers with great efficiencies. The potential applications of the modified polyethylene glycols and polyethylene oxides were explored by the preparation of novel hydrogels and solid-state electrolytes with enhancement of lithium ion conductivities. Moreover, the density functional theory calculation disclosed the plausible mechanism and explained the high selectivity for the C-H alkylation.

Suppressor mutations in Mecp2-null mice implicate the DNA damage response in Rett syndrome pathology.

Mutations in X-linked methyl-CpG-binding protein 2 (MECP2) cause Rett syndrome (RTT). To identify functional pathways that could inform therapeutic entry points, we carried out a genetic screen for secondary mutations that improved phenotypes in Mecp2/Y mice after mutagenesis with N-ethyl-N-nitrosourea (ENU). Here, we report the isolation of 106 founder animals that show suppression of Mecp2-null traits from screening 3177 Mecp2/Y genomes. Whole-exome sequencing, genetic crosses, and association analysis identified 22 candidate genes. Additional lesions in these candidate genes or pathway components associate variant alleles with phenotypic improvement in 30 lines. A network analysis shows that 63% of the genes cluster into the functional categories of transcriptional repression, chromatin modification, or DNA repair, delineating a pathway relationship with MECP2. Many mutations lie in genes that modulate synaptic signaling or lipid homeostasis. Mutations in genes that function in the DNA damage response (DDR) also improve phenotypes in Mecp2/Y mice. Association analysis was successful in resolving combinatorial effects of multiple loci. One line, which carries a suppressor mutation in a gene required for cholesterol synthesis, Sqle, carries a second mutation in retinoblastoma binding protein 8, endonuclease (Rbbp8, also known as CtIP), which regulates a DDR choice in double-stranded break (DSB) repair. Cells from Mecp2/Y mice have increased DSBs, so this finding suggests that the balance between homology-directed repair and nonhomologous end joining is important for neuronal cells. In this and other lines, two suppressor mutations confer greater improvement than one alone, suggesting that combination therapies could be effective in RTT.