Advances in the composition, efficacy, and mimicking of human milk phospholipids.

Phospholipids are the essential components of human milk, contributing to the enhancement of cognitive development, regulation of immune functions, and mitigation of elevated cholesterol levels. Infant formulas supplemented with phospholipids can change the composition, content, and globule membrane structure of milk lipids, improving their digestive properties and nutritional value. However, mimicking phospholipids in infant formulas is currently limited, and the supplemented standards of phospholipid species and amounts in infant formulas are unknown. Consequently, there is a significant difference between the phospholipids in infant formulas and those in human milk. This article reviews the recent progress in human milk phospholipid research, aiming to describe the composition, content, and positive effects of human milk phospholipids, as well as summarises the dietary sources of phospholipid supplementation and the current state of human milk phospholipid mimicking in infant formulas. This review provides clear directions for research on mimicking human milk phospholipids and evaluating the nutritional functions of phospholipids in infants.

Electrophysiological evidence of lexical processing impacted by foreign language reading anxiety.

Extensive studies have been conducted on the impact of foreign language reading anxiety on reading, primarily focusing on pedagogy and behavior but lacking electrophysiological evidence. The current study aimed to investigate the influence of foreign language reading anxiety on reading and its underlying mechanisms. The results revealed a negative correlation between foreign language reading anxiety and foreign language reading performance, irrespective of the native language. Adults with low levels of foreign language reading anxiety (LFLRA) demonstrated a significant difference in early lexical component N170 amplitude between foreign and native languages. However, this effect was not observed in adults with high levels of foreign language reading anxiety (HFLRA). In terms of N170 latency, HFLRA showed a longer N170 for the foreign language compared to the native language. Furthermore, the N170 effects were predominantly localized over the left occipitotemporal electrodes. Regarding N400 latency, a significant difference was found in LFLRA individuals between foreign and native language processing, while HFLRA individuals did not exhibit this difference. These findings suggest that HFLRA individuals experience inefficient lexical processing (such as orthography or semantics) during reading in foreign language.

Progress in triacylglycerol isomer detection in milk lipids.

In triacylglycerols (TAGs), position differences of fatty acids on the glycerol skeleton produce various TAG isomers. These TAG isomers have different pathways of digestion, absorption, and utilization in infants, thereby affecting TAG nutritional properties of TAGs. Here, we review the progress of research on methods for detecting TAG isomers, and identify direction and thought for improving these methods, including novel chromatographic combinations, perfect algorithm, and improved equipment. The ensuing optimization of these methods is expected to provide robust guarantee for the gradual improvement of milk-derived TAG isomer detection, and is an important prerequisite for infant formula to mimic the structured lipids of human milk.

Treatment Strategy for Splenic Artery Aneurysms and Novel Classification Based on Imaging.

OBJECTIVE: The incidence of splenic artery aneurysms (SAAs) has increased with advancements in imaging techniques, necessitating a comprehensive classification to guide treatment strategies. This study aims to propose a novel classification system for SAAs based on aneurysm characteristics and to review treatment outcomes at our center. METHODS: This retrospective study included 113 SAAs patients admitted at Peking Union Medical College Hospital from January 2019 to December 2023, assessed using computed tomography angiography (CTA) or digital subtraction angiography (DSA). A new classification system was devised based on the aneurysms' location, morphology, integrity, and parent artery anatomy. Treatment strategies were determined based on these characteristics, with interventions ranging from endovascular therapy to laparoscopic and open surgery. Patients were followed up post-intervention to assess mortality, complications, reinterventions, and aneurysm-related outcomes. RESULTS: The study cohort of 113 patients with 127 SAAs had a predominance of female patients (63.7%) and a mean age of 52.7 years. The SAAs were classified into five types, with Type I being the most common. The intervention techniques varied across types, with sac embolization, covered stent implantation, and artery embolization being the most frequently employed. The overall technical success rate was 94.7%, with perioperative complication and reintervention rates of 25% and 0.9%, respectively, and no deaths within 30 days post-intervention. The median follow-up duration was 21 months, with overall complications rate of 3.5% and no aneurysm-related complications or deaths. CONCLUSIONS: The proposed classification system effectively guides the selection of treatment strategies for SAAs, incorporating key anatomical and morphological features. This system facilitated high technical success and low complication rates, underscoring the importance of tailored techniques in managing SAAs. Further research is necessary to validate this classification system and optimize treatment algorithms.

Effects of a therapeutic lifestyle modification intervention on cardiometabolic health, sexual functioning and health-related quality of life in perimenopausal Chinese women: protocol for a randomised controlled trial.

INTRODUCTION: Perimenopause is a critical transitional period in reproductive ageing. A set of physiological and psychological changes can affect perimenopausal women's quality of life and further threaten their older adult health conditions. In China, less than one-third of midlife women with menopausal symptoms have actively sought professional healthcare. Regarding the public health significance of comprehensive menopause management, the current study aims to investigate the effects of a therapeutic lifestyle modification (TLM) intervention on cardiometabolic health, sexual functioning and health-related quality of life among perimenopausal Chinese women. METHOD AND ANALYSIS: A randomised controlled trial with two parallel arms will be conducted at the gynaecology outpatient department of Yunnan Provincial Hospital of Traditional Chinese Medicine in China. 94 eligible perimenopausal women aged between 40 and 55 years will be recruited for the study. The TLM intervention consists of four elements: menopause-related health education, dietary guidance, pelvic floor muscle training and Bafa Wubu Tai Chi exercise. Participants will be randomly assigned (1:1) to receive either the 12-week TLM intervention or routine care via stratified blocked randomisation. The primary outcome is quality of life; secondary outcomes of interest include sexual functioning and cardiometabolic health. The outcome measures will be assessed at baseline and post-intervention. To explore the effects of the intervention, linear mixed models will be applied to test the changes between the two groups over time in each outcome based on an intention-to-treat analysis. ETHICS AND DISSEMINATION: The Research Ethics Review Committee of Chulalongkorn University (COA No 178/66) and the Medical Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (IRB-AF-027-2022/02-02) approved the study protocol. Written informed consent will be obtained from all participants. Results will be published in peer-reviewed journals and disseminated through conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300070648.

Altered Functional Connectivity of the Multisensory Vestibular Cortex in Patients with Chronic Unilateral Vestibulopathy.

Background: Chronic unilateral vestibulopathy (CUVP) is a common chronic vestibular syndrome; the mechanisms of central vestibular compensation in CUVP are rarely studied. Methods: This study analyzed the data of 18 patients with CUVP and 18 healthy controls (HCs) and used seed-based functional connectivity (FC) and voxel-mirrored homotopic connectivity (VMHC) analyses to explore the FC alterations. Results: Compared with HCs, patients with CUVP showed decreased FC between the left dorsolateral superior frontal gyrus and the right hippocampus; the left middle frontal gyrus and the right posterior cingulate gyrus, the right hippocampus, the right parahippocampal gyrus. There is also a reduction in FC between the left and right insula. There was enhanced FC between the left supplementary motor area (SMA) and the bilateral superior occipital gyrus, the left hippocampus and the left posterior cingulate gyrus, as well as a the left middle temporal gyrus (p = 0.03). Additionally,VMHC was decreased between the bilateral medial superior frontal gyrus, the bilateral precentral gyrus, and the bilateral postcentral gyrus (p = 0.001). The zVMHC values in the bilateral superior frontal gyrus and the precentral gyrus were both negatively corrected with the Dizziness Handicap Inventory (DHI) score.well as Conclusions: Altered FC in regions of bilateral multisensory vestibular cortex existed in patients with CUVP. Decreased FC and VMHC in the bilateral multisensory vestibular cortex may affect vestibular information integration, thus affecting self-motion perception, spatial orientation, and postural control.

Fangji Huangqi Decoction alleviates rheumatoid arthritis through regulating HIF-1α mediated the angiogenesis and the balance between autophagy and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Fangji Huangqi Decoction (FHD) is frequently prescribed for the clinical treatment of wind-cold and wind-dampness pathogenic superficial deficiency syndrome. It also has a notable curative effect on rheumatoid arthritis (RA). AIM OF THE STUDY: The study aimed to explore the possible mechanism of FHD against RA and provided a theoretical basis for alternative therapies for RA. MATERIALS AND METHODS: We used UPLC-Q-TOF-MS to analysis the ingredients and absorbed blood components of FHD. At the same time, the collagen-induced arthritis (CIA) rat model was established to estimate the therapeutic effects on FHD by considering body weight, arthritis score, paw swelling, autonomous movement ability, and synovial microvessel counts. Subsequently, immunofluorescence, immunohistochemistry, and Western blot were employed to detect the anti-angiogenic capacity of FHD in vivo, as well as the levels of apoptosis and autophagy in the synovial tissue. In addition, flow cytometry and Western blot were used to assess the effects of FHD on apoptosis and autophagy in MH7A cells. The effects of FHD on the proliferation and migration of MH7A cells were measured by CCK8 assay, cell migration and, invasion experiments. Finally, a tube formation assay was performed to evaluate the angiogenic capacity of FHD in co-cultures of MH7A cells and HUVEC cells. RESULTS: Through testing of FHD's original formula, a total of 26 active ingredients have been identified, with 17 of them being absorbed into the bloodstream. FHD significantly improved the pathological symptoms and synovial hyperplasia of CIA rats. FHD could suppress the expression of HIF-1α, promote apoptosis in CIA rat synovial tissue, and suppress autophagy and angiogenesis. In vitro experiments showed that serum containing FHD inhibited the proliferation, migration, and invasion of MH7A cells, and also suppressed the expression of autophagy-related proteins while promoting apoptosis. FHD markedly repressed the expression of HIF-1α protein in TNF-α-stimulated MH7A cells and inhibited the tube formation capacity induced by MH7A cells in HUVEC cells. CONCLUSIONS: The study had proven that FHD played an excellent anti-RA role, which may be attributed to its potential mechanism of regulating the balance between autophagy and apoptosis in RA FLS by suppressing the HIF-1α, thus contributing to its anti-angiogenic activities.

In situ SERS imaging of protein-specific glycan oxidation on living cells to quantitatively visualize pathogen-cell interactions.

Glycan oxidation on the cell surface occurs in many specific life processes including pathogen-cell interactions. This work develops a surface-enhanced Raman scattering (SERS) imaging strategy for in situ quantitative monitoring of protein-specific glycan oxidation mediated pathogen-cell interactions by utilizing Raman reporter DTNB and aptamer co-assembled platinum shelled gold nanoparticles (Au@Pt-DTNB/Apt). Using Fusarium graminearum (FG) and MCF-7 cells as models, Au@Pt-DTNB/Apt can specifically bind to MUC1 protein on the cell surface containing heavy galactose (Gal) and N-acetylgalactosamine (GalNAc) modification. When FG interacts with cells, the secreted galactose oxidase (GO) can oxidize Gal/GalNAc, and the generated reactive oxygen species (ROS) further oxidizes DTNB to produce TNB for greatly enhancing the SERS signal. This strategy can quantitatively visualize for the first time both the protein-specific glycan oxidation and the mediated pathogen-cell interactions, thus providing key quantitative information to distinguish and explore the pathogen-resistance and pharmacological mechanisms of different drugs.

Glyphosate hormesis stimulates tomato (Solanum lycopersicum L.) plant growth and enhances tolerance against environmental abiotic stress by triggering nonphotochemical quenching.

BACKGROUND: Glyphosate is the most widely applied herbicide in the world. Hormesis caused by low glyphosate doses has been widely documented in many plant species. However, the specific adaptative mechanism of plants responding to glyphosate hormesis stimulation remains unclear. This study focused on the biphasic relationship between glyphosate dose and tomato plant growth, and how glyphosate hormesis stimulates plant growth and enhances tolerance to environmental stress. RESULTS: We constructed a hormesis model to describe the biphasic relationship with a maximal stimulation (MAX) of 162% above control by glyphosate at 0.063 g ha-1 . Low-dose glyphosate increased photosynthetic pigment contents and improve photosynthetic efficiency, leading to plant growth stimulation. We also found that glyphosate hormesis enhanced plant tolerance to diuron (DCMU; a representative photosynthesis inhibitor) by triggering the nonphotochemical chlorophyll fluorescence quenching (NPQ) reaction to dissipate excess energy stress from photosystem II (PSII). Transcriptomic analysis and quantitative real-time polymerase chain reaction results revealed that the photosynthesis-antenna proteins pathway was the most sensitive to glyphosate hormesis, and PsbS (encoding photosystem II subunit S), ZEP (encoding zeaxanthin epoxidase) and VDE (encoding violaxanthin de-epoxidase) involved in NPQ played crucial roles in the plant response to glyphosate hormesis. CONCLUSION: These results provide novel insights into the mechanisms of plant hormesis and is meaningful to the application of glyphosate hormesis in agriculture. © 2024 Society of Chemical Industry.

Ultra-Galactocation to Sialic Acid on Tumor Cells with A Penta-Functional Dendritic Probe for Enhanced Immune-Killing.

Glycans on tumor cell surface have significant impacts in the immune-killing process. Here an ultra-galactocation to sialic acid (Sia) strategy is designed to hugely introduce galactose (Gal) to Sia and on tumor cells in vivo by using a penta-functional dendritic probe (Den@5F), which efficiently enhances the immune-killing of tumor cells. The Den@5F contains five different kinds of functional groups, including Gal, Cy5, amino, phenylboronic acid (PBA) and 4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butanoate (mNB), which can be conveniently prepared through a two-step reaction. After injecting into the tumor-bearing mouse, Den@5F can efficiently block Sia through the specific recognition between PBA and Sia on tumor cells and hugely introduce Gal through the subsequent photo-crosslinking between mNB and amino groups to multiply conjugate excessive Den@5Fs. The comprehensively blocked Sia can prevent the immune escape, and the hugely introduced Gal can promote the immune stimulation of the immune cells, which lead to an efficient enhancement of the immune-killing. The proposed strategy provides a significant and promising tool to promote the clinical immunotherapy of tumor.

Portable, and ultrasensitive HR-HPV tests based on nucleic acid biosensors.

Cervical cancer is the third most common cancer threatening women's health globally, and high-risk human papillomavirus (HR-HPV) infection is the main cause of cervical cancer worldwide. Given the recurrent nature of HR-HPV infection, accurate screening is essential for its control. Since the commonly used polymerase chain reaction (PCR) technique is limited by professional equipment and personnel, convenient and ultrasensitive detection methods for HR-HPV are still highly needed. As new molecular detection methods, nucleic acid amplification-based biosensors have the advantages of high sensitivity, rapid operation, and portability, which are helpful for point-of-care testing in rural and remote areas. This review summarized nucleic acid biosensors for HR-HPV screening based on a variety of nucleic acid amplification strategies involved in improved PCR, loop-mediated isothermal amplification, recombinase polymerase amplification, hybridization chain reaction, catalyzed hairpin assembly, and CRISPR/Cas systems. In combination with microfluidic technology, lateral flow assays, electrochemical analysis and other sensing technologies, HR-HPV nucleic acid biosensors have the advantages of high throughput, short response time, high sensitivity and easy operation in the field. Although there are still shortcomings, such as high cost and poor reproducibility, this approach will be suitable for on-site screening of HR-HPV infection or cervical cancer and for auxiliary clinical diagnosis in complex environments and poor areas in the future.

Etiologic distribution of dizziness/vertigo in a neurological outpatient clinic according to the criteria of the international classification of vestibular disorders: a single-center study.

OBJECTIVE: The study aimed to determine the etiological characteristics of patients with dizziness/vertigo attending a neurological clinic according to the criteria of the International Classification of Vestibular Disorders (ICVD), hoping to provide a valuable reference for clinicians to diagnose and treat dizziness/vertigo. METHOD: A total of 638 consecutive patients with a chief complaint of dizziness/vertigo who attended the vertigo clinic of our neurology department from January 2019 to January 2020 were included. Clinical data of patients, including baseline data, medical history, neurological, neuro-otological, and auxiliary examination results were collected. The etiologic distribution of dizziness/vertigo was determined by analyzing the diagnoses of patients. RESULTS: Of the 638 patients with dizziness/vertigo, 38.8% were males, 61.2% were females, with a male: female ratio of 1:1.58 and a mean age of 52.9 ± 16.9 years. Benign paroxysmal positional vertigo (BPPV) was the most common cause of dizziness/vertigo in both female (38.9%) and male patients (25.5%). Subgroup analysis based on sex showed that vestibular migraine (VM) and probable autoimmune inner ear disease (p-AIED) were more prevalent in female patients (10.7% and 3.8%, respectively), while vascular vertigo/dizziness was more common in male patients (10.1%). Subgroup analysis based on age showed that the most common diseases were VM in patients aged 0-30 years (27.4%), BPPV in patients aged 31-60 years (27.1%) and 61-100 years (46.0%). Episodic vestibular syndrome (EVS) was the most commonly observed, accounting for up to 60.6% (389/638) of all patients, and the most common diagnoses were BPPV (55.3%, 215/389), VM (15.2%, 59/389), primary unilateral peripheral vestibular dysfunction (p-UPVD) of unknown etiology (11.8%, 46/389), p-AIED (4.4%, 17/389), and vascular vertigo/dizziness (2.8%, 11/389) in these patients. Chronic vestibular syndrome (CVS) was found in 14.0% (90/638) of the patients, and the most common diagnoses were persistent postural-perceptual dizziness (PPPD, 35.6%, 32/90), psychogenic dizziness (18.9%, 17/90), p-UPVD of unknown etiology (15.6%, 14/90), vascular vertigo/dizziness (15.6%, 14/90), and bilateral vestibulopathy (7.8%, 7/90). Acute vestibular syndrome (AVS) was observed in 8.4% (54/638) of the patients, and the most common diagnoses were p-UPVD of unknown etiology (31.5%, 17/54), vestibular neuritis (24.1%, 13/54), probable labyrinthine apoplexy (16.7%, 9/54), stroke (13.0%, 7/54), and psychogenic dizziness (11.1%, 6/54). 16.4% (105/638) of the patients were found to have other disorders, including 15.2% (16/105) of patients with internal diseases, and 84.8% (89/105) of patients with unknown causes. In terms of localization diagnosis, 56.1%, 17.0%, 10.0%, and 16.4% of the patients were diagnosed with peripheral vestibular disorder, central vestibular disorder, psychiatric and functional vestibular disorders, and other disorders, respectively. CONCLUSION: (1) Dizziness/vertigo was more common in females, which was frequently caused by damage to the vestibular system. Non-vestibular or unknown etiologies were also seen in some patients; (2) VM was more prevalent in women than in men, vascular vertigo/dizziness was more commonly observed in men; (3) EVS was more common in patients with dizziness/vertigo. The most common causes of dizziness/vertigo were peripheral vestibular disorders in patients with AVS and EVS, PPPD and psychogenic dizziness in patients with CVS. The most common causes were BPPV and p-UPVD of unknown etiology in patients with a peripheral vestibular disorder, VM and vascular vertigo/dizziness in patients with central vestibular disorder, PPPD and psychogenic dizziness in patients with psychiatric and functional vestibular disorders.

First report of Lasiodiplodia pseudotheobromae causing soft rot of plum in China.

Plum (Prunus salicina) is one of the most important fruit tree species worldwide (Valderrama-Soto et al. 2021). In June 2023, the postharvest soft rot symptoms were observed on plum fruits in several fruit markets of Guiyang city, Guizhou province, China. The disease incidence in these markets ranged from 20 to 25% with 70% disease severity. Plum fruits showed rotting, which was characterized by water soaked fruit tissue, softening and presence of whitish mycelia four days post inoculation. In severe conditions, whole fruits become rotted and were covered with white fungal mycelia. Small sections (5 × 3 mm) from 6 diseased plum fruits were surface sterilized by using 75% ethanol for 30 s followed by 0.1% mercuric chloride solution for 5 min, rinsed three times with ddH2O, and then transferred onto potato dextrose agar (PDA) and incubated at 25 ± 2°C for three days. Three pure cultures (GUCC23-0001 to GUCC23-0003) were obtained by transferring a single hyphal tip to new PDA plates. Colonies of these isolates were grayish-white initially, gradually turning to whitish brown with fluffy aerial mycelia and uneven edges and finally turned to a dark gray colony after five days of inoculation. The pseudoparaphyses were hyaline, cylindrical, aseptate, and rounded at apex. Conidia were ellipsoidal, hyaline, unicellular, and 24.2 to 28.6 × 12.3 to 15.5 µm in size (n = 30) (Fig. S1), which were similar to the morphology of Lasiodiplodia pseudotheobromae (Alves et al. 2008). Furthermore, fungal DNA was extracted from fresh mycelia of PDA after seven days by using fungus genomic DNA extraction kit (Biomiga, USA). Partial DNA sequences from four loci including internal transcribed spacer (ITS), translation elongation factor 1-alpha (tef1), beta-tubulin (tub2), and polymerase II second largest subunit (rpb2) were amplified with ITS1 and ITS4 (White et al. 1990), EF1-688F and EF1-1251R (Alves et al. 2008), Bt2a and Bt2b (Glass and Donaldson 1995), and RPB2-LasF and RPB2-LasR, respectively (Cruywagen et al. 2017). GenBank accession numbers are OR361680, OR361681, OR361682 for ITS, OR423394, OR423395, OR423396 for tef1, OR423397, OR423398, OR423399 for tub2, and OR423391, OR423392, OR423393 for rpb2, and gene sequencing showed 99.6 to 100% identity with ex-type strain of L. pseudotheobromae (CBS 116459). Phylogenetic analysis also placed our isolates in a highly supported clade with the reference isolate of L. pseudotheobromae (Fig. S2). Another experiment was designed to confirm the pathogenicity test for additional confirmation. Five mm mycelial plugs of L. pseudotheobromae from a three day old culture on PDA were placed on five surface-sterilized and non-wounded plum fruits for 12 hours and incubated at 25°C ± 2°C for four days. Sterilized fungus free PDA plugs were used as a negative control. Mycelial plugs were removed after 12 hours following which whole fruits were incubated in plastic boxes at 25°C ± 2°C. The experiment was repeated twice. The pathogenicity was evaluated under control conditions in laboratory (relative humidity, 70 ± 5% and temperature 25 ± 5˚C). Plum fruits showed rotting, which was characterized by water soaked fruit tissue, softening and presence of whitish mycelia four days post inoculation. These symptoms and signs were similar to the initially observed symptoms on plums in the markets. No disease symptoms were observed on the control fruits. The re-isolated fungus obtained from inoculated plum fruits was very similar to those isolated from diseased samples in morphology, fulfilling Koch's postulates. To the best of our knowledge, this is the first report of L. pseudotheobromae causing postharvest fruit rot of plum in China. In 2022, the total planting area of plum was 1946.5 thousand hectares, which produces approximately 6626300 tons of plum (Food and Agriculture Organization of the United Nations, 2022). Based on the disease incidence and severity reported in the current study, soft rot of plum may be responsible for nearly 35% of yield losses under severe. Therefore, our study laid a theoretical foundation for the prevention and control of this post-harvest disease of plum.

Controlled three-dimensional leaf-like NiCoO2@NiCo layered double hydroxide heterostructures for oxygen evolution electrocatalysts in rechargeable Zn-air batteries.

Rechargeable zinc-air batteries (ZABs) have garnered attention as a viable choice for large-scale energy storage due to their advantageous characteristics, such as high energy density and cost-effectiveness. Strategies aimed at improving the kinetics of the oxygen evolution reaction (OER) through advanced electrocatalytic materials or structural designs can significantly enhance the efficiency and longevity of ZABs. In this study, we introduce a three-dimensional (3D) leaf-vein system heterojunction architecture. In this structure, NiCoO2 nanowire arrays form the central vein, surrounded by an outer leaf composed of NiCo layered double hydroxide (LDH) nanosheets. All these components are integrated onto a substrate made of Ni foam. Notably, when tested in an alkaline environment, the NiCoO2@NiCo LDH exhibited an overpotential of 272 mV at a current density of 10 mA cm-2, and extended durability evaluations over 12 h underscored its robustness at 99.76 %. The rechargeable ZABs achieved a peak power density of 149 mW cm-2. Furthermore, the NiCoO2@NiCo LDH demonstrated stability by maintaining high round-trip efficiencies throughout more than 680 cycles (equivalent to 340 h) under galvanostatic charge-discharge cycling at 5 mA cm-2. The leaf-vein system heterojunction significantly increased the active sites of the catalysts, facilitating charge transport, improving electronic conductivity, and enhancing overall stability.

Triply Enhanced Immunotherapy via Dual Glycan Reforming Integrated with Perforation.

The enhancement of immunotherapy is an emerging direction to develop highly effective and practical cancer therapeutic methods. Here a triply enhanced immunotherapy drug (TEID) is designed for ingeniously integrating in situ dual glycan reforming with perforation on cell membrane. The TEID is composed of galactose and neuraminidase conjugated streptolysin O (SLO-Gal and SLO-NEU), which are encapsulated in a hyaluronic acid (HA) shell for targeted recognition to tumor tissue via cell surface CD44. After targeted delivery and HAase-mediated degradation in the tumor region, the TEID releases SLO-Gal and SLO-NEU, which can easily anchor Gal and NEU on the tumor cell membrane via the perforation of SLO to perform dual glycan reforming for the introduction of Gal and the cleavage of sialic acid. The former can activate immune cells to secret cytokines for immune-killing, and the latter can weaken the immune inhibition to improve the immunotherapeutic efficacy. Meanwhile, the perforation of SLO can promote the delivery of cytokines into the tumor cells to further enhance the efficacy. The designed triply enhanced immunotherapy strategy opens a significant and promising route to promote clinical immunotherapy of cancer.

Unveiling the Potential of Bacillus safensis Y246 for Enhanced Suppression of Rhizoctonia solani.

Rhizoctonia solani is a significant pathogen affecting various crops, including tobacco. In this study, a bacterial strain, namely Y246, was isolated from the soil of healthy plants and exhibited high antifungal activity. Based on morphological identification and DNA sequencing, this bacterial strain was identified as Bacillus safensis. The aim of this investigation was to explore the antifungal potential of strain Y246, to test the antifungal stability of Y246 by adjusting different cultivation conditions, and to utilize gas chromatography-mass spectrometry (GC-MS) to predict the volatile compounds related to antifungal activity in Y246. In vitro assays demonstrated that strain Y246 exhibited a high fungal inhibition rate of 76.3%. The fermentation broth and suspension of strain Y246 inhibited the mycelial growth of R. solani by 66.59% and 63.75%, respectively. Interestingly, treatment with volatile compounds derived from the fermentation broth of strain Y246 resulted in abnormal mycelial growth of R. solani. Scanning electron microscopy analysis revealed bent and deformed mycelium structures with a rough surface. Furthermore, the stability of antifungal activity of the fermentation broth of strain Y246 was assessed. Changes in temperature, pH value, and UV irradiation time had minimal impact on the antifungal activity, indicating the stability of the antifungal activity of strain Y246. A GC-MS analysis of the volatile organic compounds (VOCs) produced by strain Y246 identified a total of 34 compounds with inhibitory effects against different fungi. Notably, the strain demonstrated broad-spectrum activity, exhibiting varying degrees of inhibition against seven pathogens (Alternaria alternata, Phomopsis. sp., Gloeosporium musarum, Dwiroopa punicae, Colletotrichum karstii, Botryosphaeria auasmontanum, and Botrytis cinerea). In our extensive experiments, strain Y246 not only exhibited strong inhibition against R. solani but also demonstrated remarkable inhibitory effects on A. alternata-induced tobacco brown spot and kiwifruit black spot, with impressive inhibition rates of 62.96% and 46.23%, respectively. Overall, these findings highlight the significant antifungal activity of B. safensis Y246 against R. solani. In addition, Y246 has an excellent antifungal stability, with an inhibition rate > 30% under different treatments (temperature, pH, UV). The results showed that the VOCs of strain Y246 had a strong inhibitory effect on the colony growth of R. solani, and the volatile substances produced by strain Y246 had an inhibitory effect on R. solani at rate of 70.19%. Based on these results, we can conclude that Y246 inhibits the normal growth of R. solani. These findings can provide valuable insights for developing sustainable agricultural strategies.

Delayed step-by-step decompression with DSF alleviates skeletal muscle crush injury by inhibiting NLRP3/CASP-1/GSDMD pathway.

Crush injury (CI) is a common disease in earthquake and traffic accidents. It refers to long-term compression that induces ischemia and hypoxia injury of skeletal muscle rich parts, leading to rupture of muscle cells and release of contents into the blood circulation. Crush syndrome (CS) is the systemic manifestation of severe, traumatic muscle injury. CI rescue faces a dilemma. Ischemic reperfusion due to decompression is a double-edged sword for the injured. Death often occurs when the injured are glad to be rescued. Programmed cell death (PCD) predominates in muscle CI or ischemia-reperfusion injury. However, the function and mechanism of pyroptosis and apoptosis in the pathogenesis of skeletal muscle injury in CI remain elusive. Here, we identified that pyroptosis and apoptosis occur independently of each other and are regulated differently in the injured mice's skeletal muscle of CI. While in vitro model, we found that glucose-deprived ischemic myoblast cells could occur pyroptosis. However, the cell damage degree was reduced if the oxygen was further deprived. Then, we confirmed that delayed step-by-step decompression of CI mice could significantly reduce skeletal muscle injury by substantially inhibiting NLRP3/Casp-1/GSDMD pyroptosis pathway but not altering the Casp-3/PARP apoptosis pathway. Moreover, pyroptotic inhibitor DSF therapy alone, or the combination of delayed step-by-step decompression and pyroptotic inhibitor therapy, significantly alleviated muscle injury of CI mice. The new physical stress relief and drug intervention method proposed in this study put forward new ideas and directions for rescuing patients with CI, even CS-associated acute kidney injury (CS-AKI).

Comparison study on enhancement of phosphorus recovery from low-strength wastewater treated with different magnesium-based electrochemical constructed wetland.

Phosphorus (P) recovery from wastewaters treated with constructed wetlands (CWs) could alleviate the current global P crisis but has not received sufficient attention. In this study, P transformation in different magnesium-based electrochemical CWs, including micro-electrolysis CW (M-CW), primary battery CW (P-CW), and electrolysis CW (E-CW), was thoroughly examined. The results revealed that the P removal efficiency was 53.0%, 75.8%, and 61.9% in the M-CW, E-CW, and P-CW, respectively. P mass balance analysis showed that P electrode deposition was the main reason for the higher P removal in the E-CW and P-CW. Significant differences were found between the E-CW and P-CW, P was distributed primarily on the magnesium plate in the P-CW but was distributed on the carbon plate in the E-CW. The E-CW had excellent P recovery capacity, and struvite was the major P recovery product. More intense magnesium plate corrosion and alkaline environment increased struvite precipitation in the E-CW, with the proportion of 61.6%. The results of functional microbial community analysis revealed that the abundance of electroactive bacteria was positively correlated with the deposition of struvite. This study provided an essential reference for the targeted electrochemical regulation of electric field processes and microorganisms in CWs to enhance P recovery.