Efficacy of robot-assisted thoracoscopic surgery in the treatment of pulmonary sequestration in children.

Objective: This study was performed to evaluate the efficacy of robot-assisted thoracoscopic surgery (RATS) in the treatment of pulmonary sequestration (PS) in children. Methods: All video-assisted thoracoscopic surgery (VATS) and RAST performed on patients with PS at a single center from May 2019 to July 2023 were identified. The χ 2 and Wilcoxon tests were used to compare the perioperative outcomes between VATS and RATS groups. Results: Ninety-three patients underwent RATS while 77 patients underwent VATS. In both two groups, one patient converted to thoracotomy and no surgical mortality case. The median operation time was longer for the RATS group compared with the VATS group (75 min vs. 60 min, p <0.001). A lower ratio of chest tube indwelling (61.3% vs. 90.9%, p <0.001), fewer drainage days (1.0 day vs. 2.0 days, p <0.001), and a shorter postoperative length of stay (5.0 days vs. 6.0 days, p <0.001) were found in the RATS group than that in the VATS group. No significant difference was found in the incidence of short-term postoperative complications (hydrothorax and pneumothorax) between two groups. Conclusions: RATS was safe and effective in children with PS over 6 months old and more than 7 kg. Furthermore, RATS led to better short-time postoperative outcome than VATS. Multi-institutional studies are warranted to compare differences in long-term outcomes between RATS and VATS.

Effect of mutation of phaC on carbon supply, extracellular polysaccharide production, and pathogenicity of Xanthomonas oryzae pv. oryzae.

Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight in rice. Polyhydroxyalkanoates (PHAs) consitute a diverse group of biopolyesters synthesized by bacteria under nutrient-limited conditions. The phaC gene is important for PHA polymerization. We investigated the effects of phaC gene mutagensis in Xoo strain PXO99A. The phaC gene knock-out mutant exhibited reduced swarming ability relative to that of the wild-type. Under conditions where glucose was the sole sugar source, extracellular polysaccharide (EPS) production by ΔphaC declined by 44.8%. ΔphaC showed weak hypersensitive response (HR) induction in the leaves of non-host Nicotiana tabacum, concomitant with downregulation of hpa1 gene expression. When inoculated in rice leaves by the leaf-clipping method, ΔphaC displayed reduced virulence in terms of lesion length compared with the wild-type strain. The complemented strain showed no significant difference from the wild-type strain, suggesting that the deletion of phaC in Xoo induces significant alterations in various physiological and biological processes. These include bacterial swarming ability, EPS production, transcription of hrp genes, and glucose metabolism. These changes are intricately linked to the energy utilization and virulence of Xoo during plant infection. These findings revealed involvement of phaC in Xoo is in the maintaining carbon metabolism by functioning in the PHA metabolic pathway.

Integrative analysis of bulk and single-cell RNA sequencing reveals the gene expression profile and the critical signaling pathways of type II CPAM.

BACKGROUD: Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets. METHODS: RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations. RESULTS: A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition. CONCLUSIONS: In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.

Concise synthesis of chiral γ-butenolides via an allylation/lactonization cascade reaction.

A highly enantioselective allylation/lactonization cascade was developed, which provides a concise and efficient route to chiral γ-butenolides under mild conditions. Most of the reaction examples can be completed in 10 minutes with high selectivity.

Disrupting TSLP-TSLP receptor interactions via putative small molecule inhibitors yields a novel and efficient treatment option for atopic diseases.

Thymic stromal lymphopoietin (TSLP) is a key player in atopic diseases, which has sparked great interest in therapeutically targeting TSLP. Yet, no small-molecule TSLP inhibitors exist due to the challenges of disrupting the protein-protein interaction between TSLP and its receptor. Here, we report the development of small-molecule TSLP receptor inhibitors using virtual screening and docking of >1,000,000 compounds followed by iterative chemical synthesis. BP79 emerged as our lead compound that effectively abrogates TSLP-triggered cytokines at low micromolar concentrations. For in-depth analysis, we developed a human atopic disease drug discovery platform using multi-organ chips. Here, topical application of BP79 onto atopic skin models that were co-cultivated with lung models and Th2 cells effectively suppressed immune cell infiltration and IL-13, IL-4, TSLP, and periostin secretion, while upregulating skin barrier proteins. RNA-Seq analysis corroborate these findings and indicate protective downstream effects on the lungs. To the best of our knowledge, this represents the first report of a potent putative small molecule TSLPR inhibitor which has the potential to expand the therapeutic and preventive options in atopic diseases.

Relationship between remnant cholesterol and short-term prognosis in acute ischemic stroke patients.

OBJECTIVE: Several studies have illustrated that elevated RC levels are related to a heightened risk of acute ischemic stroke (AIS). Our research aimed to explore the correlation between RC levels and poor prognosis after a 90-day interval in AIS patients. METHODS: A total of 287 individuals were enrolled in the study, the primary outcome was defined as poor prognosis. RC was derived by the exclusion of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) from total cholesterol (TC). RESULTS: Following the screening process, 253 AIS patients were included in the study, presenting a median age of 66[57, 75] years. Upon stratifying RC levels into quartiles, those in the top quartile faced a greater likelihood of diabetes diagnosis (42.86%, p = .014) and experienced a higher rate of unfavorable outcomes after 90 days (36.51%, p = .001). After accounting for confounding factors, the correlation between the fourth quartile of RC levels and the amplified likelihood of poor prognosis remained significant (odds ratio (OR) 8.471, 95% confidence interval (CI) (1.841, 38.985); p = .006). Analysis of subgroups unveiled a notable correlation between higher RC levels and poor 90-day prognosis, particularly in individuals with elevated NIHSS scores (p = .044). A progressively increasing 90-day risk of poor prognosis after an RC greater than 0.38 mmol/L was visualized by restricted cubic spline plots (p-overall = .011). CONCLUSIONS: Including RC as a contributing element may refine the prediction of poor 90-day prognosis for AIS patients. Integrating RC with traditional risk factors can potentially enhance the predictive value for cerebrovascular disease.

Left ventricular systolic dysfunction predicts clinical prognosis in patients with acute ischemic stroke after intravenous thrombolysis.

BACKGROUND: Although intravenous recombinant tissue plasminogen activator (rt-PA) thrombolysis is the most effective early treatment for acute ischemic stroke (AIS), outcomes vary greatly among patients. Left ventricular systolic dysfunction (LVSD) is prone to distant organ ischemia and may be a predictor for poor prognosis in AIS patients undergoing intravenous thrombolysis (IVT). Our aim was to investigate the predictivity of LVSD diagnosis (as measured by left ventricular ejection fraction (LVEF)) on 90-day clinical outcomes in AIS patients undergoing thrombolysis. METHODS: The current prospective cohort study continuously enrolled 273 AIS patients from the National Stroke Prevention and Treatment Engineering Management Special Database who underwent IVT and completed echocardiography within 24 h of admission between 2021 and 2023. LVSD was examined by evaluation of the echocardiographic LVEF values using Simpson's biplane method of discs in line with international guidelines, and defined as a LVEF value < 50%. Multivariable ordinal logistic regression model was performed to analyze the association between LVEF and functional outcome at 3 months. Restricted cubic spline (RCS) was used to examine the shape of the dose-response association between reduced LVEF and poor functional outcomes. Subgroup analysis was also employed to further verify the reliability and practicability of the results. RESULTS: Baseline data analysis showed LVSD patients had more comorbidities including on multivariate analyses, LVSD (OR 2.78, 95% CI 1.23 to 6.24, P=0.014), pre-existing diabetes mellitus (OR 2.08, 95% CI 1.11 to 3.90, P=0.023) and NIHSS on arrival (OR 1.31, 95% CI 1.21 to 1.49, P<0.001) were independent predictors of poor functional outcomes (mRS ≥ 3) at 3 months. Multivariable-adjusted spline regression indicated a linear dose-response association between LVEF after IVT and poor functional outcomes (p for linearity < 0.001), with the optimal cutoff values of LVEF being 0.48. CONCLUSIONS: Our finding indicated that AIS patients with LVSD after IVT had poorer outcomes, suggesting the need to monitor and optimize LVEF in stroke management.

Active secretion of IL-33 from astrocytes is dependent on TMED10 and promotes central nervous system homeostasis.

Interleukin-33 (IL-33), secreted by astrocytes, regulates the synapse development in the spinal cord and hippocampus and suppresses autoimmune disease in the central nervous system (CNS). However, the mechanism of unconventional protein secretion of this cytokine remains unclear. In this study, we found that IFN-γ promotes the active secretion of IL-33 from astrocytes, and the active secretion of IL-33 from cytoplasm to extracellular space was dependent on interaction with transmembrane emp24 domain 10 (TMED10) via the IL-1 like cytokine domain in astrocytes. Knockout of Il-33 or its receptor St2 induced hippocampal astrocyte activation and depressive-like disorder in naive mice, as well as increased spinal cord astrocyte activation and polarization to a neurotoxic reactive subtype and aggravated passive experimental autoimmune encephalomyelitis (EAE). Our results have identified that IL-33 is actively secreted by astrocytes through the unconventional protein secretion pathway facilitated by TMED10 channels. This process helps maintain CNS homeostasis by inhibiting astrocyte activation.

Intranasal delivery of low-dose anti-CD124 antibody enhances treatment of chronic rhinosinusitis with nasal polyps.

Frequent injections of anti-CD124 monoclonal antibody (αCD124) over long periods of time are used to treat chronic rhinosinusitis with nasal polyps (CRSwNP). Needle-free, intranasal administration (i.n.) of αCD124 is expected to provide advantages of localized delivery, improved efficacy, and enhanced medication adherence. However, delivery barriers such as the mucus and epithelium in the nasal tissue impede penetration of αCD124. Herein, two novel protamine nanoconstructs: allyl glycidyl ether conjugated protamine (Nano-P) and polyamidoamine-linked protamine (Dendri-P) were synthesized and showed enhanced αCD124 penetration through multiple epithelial layers compared to protamine in mice. αCD124 was mixed with Nano-P or Dendri-P and then intranasally delivered for the treatment of severe CRSwNP in mice. Micro-CT and pathological changes in nasal turbinates showed that these two nano-formulations achieved ∼50 % and ∼40 % reductions in nasal polypoid lesions and eosinophil count, respectively. Both nano-formulations provided enhanced efficacy in suppressing nasal and systemic Immunoglobulin E (IgE) and nasal type 2 inflammatory biomarkers, such as interleukin 13 (IL-13) and IL-25. These effects were superior to those in the protamine formulation group and subcutaneous (s.c.) αCD124 given at a 12.5-fold higher dose. Intranasal delivery of protamine, Nano-P, or Dendri-P did not induce any measurable toxicities in mice.

Burst-Enhanced Super-Resolution Network (BESR).

Multi-frame super-resolution (MFSR) leverages complementary information between image sequences of the same scene to increase the resolution of the reconstructed image. As a branch of MFSR, burst super-resolution aims to restore image details by leveraging the complementary information between noisy sequences. In this paper, we propose an efficient burst-enhanced super-resolution network (BESR). Specifically, we introduce Geformer, a gate-enhanced transformer, and construct an enhanced CNN-Transformer block (ECTB) by combining convolutions to enhance local perception. ECTB efficiently aggregates intra-frame context and inter-frame correlation information, yielding an enhanced feature representation. Additionally, we leverage reference features to facilitate inter-frame communication, enhancing spatiotemporal coherence among multiple frames. To address the critical processes of inter-frame alignment and feature fusion, we propose optimized pyramid alignment (OPA) and hybrid feature fusion (HFF) modules to capture and utilize complementary information between multiple frames to recover more high-frequency details. Extensive experiments demonstrate that, compared to state-of-the-art methods, BESR achieves higher efficiency and competitively superior reconstruction results. On the synthetic dataset and real-world dataset of BurstSR, our BESR achieves PSNR values of 42.79 dB and 48.86 dB, respectively, outperforming other MFSR models significantly.

Dynamic flow for efficient partial decellularization of tracheal grafts: A preliminary rabbit study.

Objective: Bioengineered tracheal grafts are a potential solution for the repair of long-segment tracheal defects. A recent advancement is partially decellularized tracheal grafts (PDTGs) which enable regeneration of host epithelium and retain viable donor chondrocytes for hypothesized benefits to mechanical properties. We propose a novel and tunable 3D-printed bioreactor for creating large animal PDTG that brings this technology closer to the bedside. Methods: Conventional agitated immersion with surfactant and enzymatic activity was used to partially decellularize New Zealand white rabbit (Oryctolagus cuniculus) tracheal segments (n = 3). In parallel, tracheal segments (n = 3) were decellularized in the bioreactor with continuous extraluminal flow of medium and alternating intraluminal flow of surfactant and medium. Unprocessed tracheal segments (n = 3) were also collected as a control. The grafts were assessed using the H&E stain, tissue DNA content, live/dead assay, Masson's trichrome stain, and mechanical testing. Results: Conventional processing required 10 h to achieve decellularization of the epithelium and submucosa with poor chondrocyte viability and mechanical strength. Using the bioreactor reduced processing time by 6 h and resulted in chondrocyte viability and mechanical strength similar to that of native trachea. Conclusion: Large animal PDTG created using our novel 3D printed bioreactor is a promising approach to efficiently produce tracheal grafts. The bioreactor offers flexibility and adjustability favorable to creating PDTG for clinical research and use. Future research includes optimizing flow conditions and transplantation to assess post-implant regeneration and mechanical properties. Level of Evidence: NA.

Efficacy of Da Vinci Robot-assisted Thoracoscopic Surgery in Children With Congenital Cystic Adenomatiod Malformation.

BACKGROUND: Surgical intervention is advisable for both asymptomatic and symptomatic CCAM children. This study aims to compare and analyze the efficacy of thoracoscopic and Da Vinci robot-assisted procedures in the management of CCAM among pediatric patients. METHODS: The clinical data of 188 pediatric patients diagnosed with CCAM and admitted to the Children's Hospital, Zhejiang University School of Medicine, from April 2019 to April 2023 were retrospectively analyzed. The Clavien-Dindo classification was employed for the systematic categorization of postoperative complications. RESULTS: The demographic and clinical characteristics of the patients were comparable between the two groups. Postoperative outcomes, such as the chest tube indwelling rate (92.6% vs 36.2%, p < 0.001∗), chest tube duration (2.0 (2.0-3.0) days vs 1.0 (1.0-2.0) days, p < 0.001∗), and length of postoperative hospital stay (6.0 (5.0-7.0) days vs 5.0 (5.0-6.0) days, p < 0.001∗), favored RATS over VATS. Additionally, there was no significant difference in complications between the two group, but the p-value is in a critical state. Ⅲa complications (mainly composed of postoperative thoracentesis procedures) manifesting as a higher rate in the RATS, nearly double that observed in the VATS. CONCLUSIONS: Robot-assisted thoracoscopic lung resection is demonstrated to be safe and feasible, with notable advantages in short-term postoperative clinical outcomes. Nevertheless, the practicality and long-term benefits of this technique necessitate further refinement and dedicated study. LEVEL OF EVIDENCE: LEVEL III.

Relation between frailty and adverse outcomes in elderly patients with gastric cancer: a scoping review.

Background: Playing an exemplary role, frailty have crucial effect on the preoperative evaluation of elderly patients. Previous studies have shown that frailty is associated with complications and mortality in patients with gastric cancer (GC). However, with the development of the concept of "patient-centered", the range of health-related outcomes is broad. The differences in relation between frailty and various adverse outcomes will be further explored. Method: The PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wan Fang, and Chinese Biomedical Literature databases were searched for keywords, including frailty (such as frail) and gastric cancer (such as stomach neoplasms or stomach cancer or gastrectomy or gastric surgery). The search period is until August 2023. The included studies were observational or cohort studies with postoperative related adverse outcomes as primary or secondary outcome measures. Valid assessment tools were used. The Quality Assessment Tool for Observational Cohort and Cross-sectional Studies was used to assess methodological quality in the included literature. Result: Fifteen studies were included, including 4 cross-sectional studies, 8 retrospective cohort studies, and 3 prospective cohort studies. Among them, 6 studies were rated as "Good" and 9 studies were rated as "Fair," indicating that the quality of the literature was high. Then, 10 frailty assessment tools were summarized and classified into two broad categories in accordance with frailty models. Results of the included studies indicated that frailty in elderly patients with GC was associated with postoperative complications, mortality, hospital days, readmissions, quality of life, non-home discharge, and admission to the intensive care unit. Conclusion: This scoping review concludes that high levels of preoperative frailty increase the risk of adverse outcomes in elderly patients with GC. Frailty will be widely used in the future clinical evaluation of elderly gastric cancer patients, precise risk stratification should be implemented for patients, and frailty management should be implemented well to reduce the occurrence of adverse treatment outcomes.

Bidirectional relationship between late-onset epilepsy (LOE) and dementia: A systematic review and meta-analysis of cohort studies.

OBJECTIVE: To explore the bidirectional relationship of late-onset epilepsy (LOE) with dementia and Alzheimer's disease (AD). METHODS: Using the common electronic databases, including PubMed, Cochrane Library databases and EMBASE, we systematically reviewed published cohort studies that assessed the risk of LOE in individuals comorbid with dementia or AD, and those with dementia or AD comorbid with LOE that had been published up to 31 March 2023. The data extraction process was carried out independently by two authors. The summary adjusted relative ratio (aRR) was calculated by employing Rev Man 5.3 for the inclusion of studies. To investigate the origins of heterogeneity, we conducted both subgroup and sensitivity analyses. In the presence of heterogeneity, a random-effects model was employed. To evaluate potential publication bias, we utilized the funnel plot and conducted Begg's and Egger's tests. RESULTS: We included 20 eligible studies in the final analysis after a rigorous screening process. Pooled results indicated that LOE was association with an increased risk of all-cause dementia (aRR: 1.34, 95% confidence interval [CI]: 1.13-1.59) and AD (aRR: 2.49, 95% CI: 1.16-5.32). In addition, the pooled effect size for LOE associated with baseline AD and all-cause dementia were 3.51 (95% CI: 3.47-3.56) and 2.53 (95% CI: 2.39-2.67), respectively. Both sensitivity and subgroup analyses showed that these positive correlations persisted. According to the results of the Egger's and Begg's tests, as well as visual inspection of funnel plots, none of the studies appeared to be biased by publication. CONCLUSION: The findings suggested that LOE is a potential risk factor for dementia and AD, and vice versa, dementia and AD are both potential risk indicators for LOE. Since there is substantial heterogeneity among the cohorts analyzed and more cohort studies should be conducted to confirm the correlations found in the current study.

Prognostic Significance of Uric Acid Levels in Intracerebral Hemorrhage Patients.

Background and Purpose: The role of serum uric acid (UA) level in patients suffering from stroke remains controversial. Our aim was to investigate the effect of UA level on clinical outcomes in patients with intracerebral hemorrhage (ICH). Methods: In the retrospective cohort study, we analyzed data from 250 patients with intracerebral hemorrhage (85 women and 165 men) to investigate the difference in UA levels between patients with a good prognosis and those with a poor prognosis. Additionally, we analyzed the impact of UA levels on the risk of short-time prognosis of ICH patients. Results: Patients with a good prognosis presented with significantly lower levels of UA (348.71 ± 84.97 µmol/L) than those with poor prognosis (393.06 ± 148.46 µmol/L). Furthermore, multivariate logistic regression model demonstrated that a high UA level was a likely risk factor for worse prognosis among patients suffering in ICH (odds ratio [95% confidence interval], 1.006 [1.0012, 1.0108]; P = 0.015). Additionally, UA has a threshold effect value of 363.9 µmol/L and was presented in levels that were in a nonlinear relationship with incidence rate of short-time prognosis outcome of ICH patients. Conclusion: Our findings indicate that higher UA levels can increase the risk of poor clinical prognosis in patients with ICH and high UA levels are not conductive to the clinical prognosis of patients with ICH. These findings provide a new perspective on the treatment and prevention of ICH.

Perceptions of community care among nursing students: A cross-sectional study with implications to nursing workforce.

BACKGROUND: A shift of health care services towards community care has driven the need to develop the community care nursing workforce. However, challenges exist in attracting nursing graduates to a career in community care. AIM: To examine perceptions of community care and placement preference among undergraduate nursing students across different years of study in a Singapore university. METHODS: This study examined perceptions of community care and placement preference among undergraduate nursing students across different years of study. A cross-sectional study was conducted using the 'Scale on COmmunity care Perceptions' (SCOPE). RESULTS: Only 31.3 % of the 501 nursing students who completed the survey preferred community care placement. They rated opportunities for advancement, work status and enthusiastic colleagues in community care with relatively lower scores in the SCOPE. Students' placement preferences and year of study were predictive factors of their perceptions of community care nursing. Students who indicated their placement preference in home-based care (p < 0.001) and intermediate long-term care (p < 0.05) reported significantly positive perceptions towards community nursing as compared to students who indicated acute care as their preferred placement. Despite pre-perceived ideas among the year 1 cohort, the community care placement within their course curriculum had an impact on year 2 to 4 students' perceptions of community care. CONCLUSIONS: These findings identified key strategies to increase the community care nursing workforce which include promoting a better understanding of the role of a community nurse, providing quality community placement opportunities supported by preceptors who are good role models and fostering an optimistic career outlook and advancement in community nursing.

Enantioselective sulfonylation to construct 3-sulfonylated oxindoles.

Asymmetric synthesis of 3-sulfonylated 3-substituted oxindoles through the addition of sodium sulfinate salts to 3-bromo-3-substituted oxindoles has been achieved using chiral nickel complexes of N,N'-dioxides. This method facilitates the creation of diverse chiral sulfonyl oxindoles, several of which display promising anticancer properties. Notably, the catalyst demonstrates remarkable tolerance to water, crucial for maintaining enantioselectivity. Furthermore, the utilization of topographic steric maps of the catalysts offers valuable insights into the mechanism underlying enantioselection reversal.

Fusarium graminearum rapid alkalinization factor peptide negatively regulates plant immunity and cell growth via the FERONIA receptor kinase.

The plant rapid alkalinization factor (RALF) peptides function as key regulators in cell growth and immune responses through the receptor kinase FERONIA (FER). In this study, we report that the transcription factor FgPacC binds directly to the promoter of FgRALF gene, which encodes a functional homologue of the plant RALF peptides from the wheat head blight fungus Fusarium graminearum (FgRALF). More importantly, FgPacC promotes fungal infection via host immune suppression by activating the expression of FgRALF. The FgRALF peptide also exhibited typical activities of plant RALF functions, such as inducing plant alkalinization and inhibiting cell growth, including wheat (Triticum aestivum), tomato (Solanum lycopersicum) and Arabidopsis thaliana. We further identified the wheat receptor kinase FERONIA (TaFER), which is capable of restoring the defects of the A. thaliana FER mutant. In addition, we found that FgRALF peptide binds to the extracellular malectin-like domain (ECD) of TaFER (TaFERECD) to suppress the PAMP-triggered immunity (PTI) and cell growth. Overexpression of TaFERECD in A. thaliana confers plant resistance to F. graminearum and protects from FgRALF-induced cell growth inhibition. Collectively, our results demonstrate that the fungal pathogen-secreted RALF mimic suppresses host immunity and inhibits cell growth via plant FER receptor. This establishes a novel pathway for the development of disease-resistant crops in the future without compromising their yield potential.

Systemic delivery of proteins using novel peptides via the sublingual route.

Therapeutic proteins often require needle-based injections, which compromise medication adherence especially for those with chronic diseases. Sublingual administration provides a simple and non-invasive alternative. Herein, two novel peptides (lipid-conjugated protamine and a protamine dimer) were synthesized to enable sublingual delivery of proteins through simple physical mixing with the payloads. It was found that the novel peptides promoted intracellular delivery of proteins via increased pore formation on the cell surface. Results from in vitro models of cell spheroids and human sublingual tissue substitute indicated that the novel peptides enhanced protein penetration through multiple cell layers compared to protamine. The novel peptides were mixed with insulin or semaglutide and sublingually delivered to mice for blood glucose (BG) control. The effects of these sublingual formulations were comparable to the subcutaneous preparations and superior to protamine. In addition to peptide drugs, the novel peptides were shown to enable sublingual absorption of larger proteins with molecular weights from 22 to 150 kDa in mice, including human recombinant growth hormone (rhGH), bovine serum albumin (BSA) and Immunoglobulin G (IgG). The novel peptides given sublingually did not induce any measurable toxicities in mice.

Simple Binding and Dissociation of a Sialoglycoprotein Using Boronic Acid-Modified Functional Interfaces on Microparticles.

An overexpression of sialic acid is an indicator of metastatic cancer, and selective detection of sialic acid shows potential for cancer diagnosis. Boronic acid is a promising candidate for this purpose because of its ability to specifically bind to sialic acid under acidic conditions. Notably, the binding strength can be easily modulated by adjusting the pH, which allows for a simple dissociation of the bound sialic acid. In this study, we developed 5-boronopicolinic acid (5-BPA)-modified magnetic particles (BMPs) to selectively capture sialic acid biomolecules. We successfully captured fetuin, a well-known sialoglycoprotein, on BMPs at >104 molecules/particle using an acetate buffer (pH 5.0). Facile dissociation then occurred when the system was changed to a pH 7.6 phosphate buffer. This capture-and-release process could be repeated at least five times. Moreover, this system could enrich fetuin by more than 20 times. In summary, BMPs are functional particles for facile purification and concentration through the selective capture of sialic acid proteins and can improve detection sensitivity compared with conventional methods. This technology shows potential for the detection of sialic acid overexpression by biological particles.