O-GlcNAcylation promotes tumor immune evasion by inhibiting PD-L1 lysosomal degradation.

Programmed-death ligand 1 (PD-L1) and its receptor programmed cell death 1 (PD-1) mediate T cell-dependent immunity against tumors. The abundance of cell surface PD-L1 is a key determinant of the efficacy of immune checkpoint blockade therapy targeting PD-L1. However, the regulation of cell surface PD-L1 is still poorly understood. Here, we show that lysosomal degradation of PD-L1 is regulated by O-linked N-acetylglucosamine (O-GlcNAc) during the intracellular trafficking pathway. O-GlcNAc modifies the hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), a key component of the endosomal sorting machinery, and subsequently inhibits its interaction with intracellular PD-L1, leading to impaired lysosomal degradation of PD-L1. O-GlcNAc inhibition activates T cell-mediated antitumor immunity in vitro and in immune-competent mice in a manner dependent on HGS glycosylation. Combination of O-GlcNAc inhibition with PD-L1 antibody synergistically promotes antitumor immune response. We also designed a competitive peptide inhibitor of HGS glycosylation that decreases PD-L1 expression and enhances T cell-mediated immunity against tumor cells. Collectively, our study reveals a link between O-GlcNAc and tumor immune evasion, and suggests strategies for improving PD-L1-mediated immune checkpoint blockade therapy.

O-GlcNAcylation regulates epidermal growth factor receptor intracellular trafficking and signaling.

SignificanceEpidermal growth factor receptor (EGFR) is one of the most important membrane receptors that transduce growth signals into cells to sustain cell growth, proliferation, and survival. EGFR signal termination is initiated by EGFR internalization, followed by trafficking through endosomes, and degradation in lysosomes. How this process is regulated is still poorly understood. Here, we show that hepatocyte growth factor regulated tyrosine kinase substrate (HGS), a key protein in the EGFR trafficking pathway, is dynamically modified by a single sugar N-acetylglucosamine. This modification inhibits EGFR trafficking from endosomes to lysosomes, leading to the accumulation of EGFR and prolonged signaling. This study provides an important insight into diseases with aberrant growth factor signaling, such as cancer, obesity, and diabetes.

Theoretical Prediction of Monolayer BeP2O4H4 with Excellent Nonlinear-Optical Properties in Deep-Ultraviolet Range.

Most 2D nonlinear optical (NLO) materials do not have an ultrawide bandgap, therefore, they are unsuitable for working in the deep-ultraviolet spectral range (< 200 nm). Herein, the theoretical prediction of an excellent monolayer BeP2O4H4 (ML-BPOH) is reported. DFT analyses suggest a low cleavage energy (≈45 meV per atom) from a naturally existed bulk-BPOH material, indicating feasible exfoliation. This novel 2D material exhibits excellent properties including an ultrawide bandgap (Eg) of 7.84 eV, and a strong second-order nonlinear susceptibility ( d b u l k e f f $d_{bulk}^{eff}$ = 0.43 pm V-1), which is comparable to that of benchmark bulk-KBBF crystal (d16 = 0.45 pm V-1). The wide bandgap and large SHG effect of ML-BPOH are mainly derived from the (PO2H2)- tetrahedron. Notably, ML-BPOH exhibits an outstanding 50% variation in dsheet under minor stress stimuli (±3%) due to rotation of structurally rigid (PO2H2)- tetrahedron. This indicates significant potential for application in material deformation monitoring.

O-GlcNAcylation promotes pancreatic tumor growth by regulating malate dehydrogenase 1.

Oncogenic Kras-activated pancreatic ductal adenocarcinoma (PDAC) cells highly rely on an unconventional glutamine catabolic pathway to sustain cell growth. However, little is known about how this pathway is regulated. Here we demonstrate that Kras mutation induces cellular O-linked ß-N-acetylglucosamine (O-GlcNAc), a prevalent form of protein glycosylation. Malate dehydrogenase 1 (MDH1), a key enzyme in the glutamine catabolic pathway, is positively regulated by O-GlcNAcylation on serine 189 (S189). Molecular dynamics simulations suggest that S189 glycosylation on monomeric MDH1 enhances the stability of the substrate-binding pocket and strengthens the substrate interactions by serving as a molecular glue. Depletion of O-GlcNAcylation reduces MDH1 activity, impairs glutamine metabolism, sensitizes PDAC cells to oxidative stress, decreases cell proliferation and inhibits tumor growth in nude mice. Furthermore, O-GlcNAcylation levels of MDH1 are elevated in clinical PDAC samples. Our study reveals that O-GlcNAcylation contributes to pancreatic cancer growth by regulating the metabolic activity of MDH1.

Sialic Acid-Modified O-GlcNAc Transferase Inhibitor Liposome Presents Antitumor Effect in Hepatocellular Carcinoma.

O-linked-N-acetylglucosaminylation (O-GlcNAcylation) plays a key role in hepatocellular carcinoma (HCC) development, and the inhibition of O-GlcNAcylation has therapeutic potential. To decrease the systemic adverse events and increase targeting, we used sialic acid (SA)-decorated liposomes loaded with OSMI-1, an inhibitor of the O-GlcNAcylation, to further improve the anti-HCC effect. Fifty pairs of HCC tissue samples and the cancer genome atlas database were used to analyze the expression of O-GlcNAc transferase (OGT) and its effects on prognosis and immune cell infiltration. OSMI-1 cells were treated with SA and liposomes. Western blotting, immunofluorescence, cell proliferation assay, flow cytometry, enzyme-linked immunosorbent assay, immunohistochemistry, and tumorigenicity assays were used to investigate the antitumor effect of SA-modified OSMI-1 liposomes in vitro and in vivo. OGT was highly expressed in HCC tissues, negatively correlated with the degree of tumor infiltration of CD8+ and CD4+T cells and prognosis, and positively correlated with the degree of Treg cell infiltration. SA-modified OSMI-1 liposome (OSMI-1-SAL) was synthesized with stable hydrodynamic size distribution. Both in vitro and in vivo, OSMI-1-SAL exhibited satisfactory biosafety and rapid uptake by HCC cells. Compared to free OSMI-1, OSMI-1-SAL had a stronger capacity for suppressing the proliferation and promoting the apoptosis of HCC cells. Moreover, OSMI-1-SAL effectively inhibited tumor initiation and development in mice. OSMI-1-SAL also promoted the release of damage-associated molecular patterns, including anticalreticulin, high-mobility-group protein B1, and adenosine triphosphate, from HCC cells and further promoted the activation and proliferation of the CD8+ and CD4+T cells. In conclusion, the OSMI-1-SAL synthesized in this study can target HCC cells, inhibit tumor proliferation, induce tumor immunogenic cell death, enhance tumor immunogenicity, and promote antitumor immune responses, which has the potential for clinical application in the future.

The protein phosphatase PPM1A dephosphorylates and activates YAP to govern mammalian intestinal and liver regeneration.

The Hippo-YAP pathway responds to diverse environmental cues to manage tissue homeostasis, organ regeneration, tumorigenesis, and immunity. However, how phosphatase(s) directly target Yes-associated protein (YAP) and determine its physiological activity are still inconclusive. Here, we utilized an unbiased phosphatome screening and identified protein phosphatase magnesium-dependent 1A (PPM1A/PP2Cα) as the bona fide and physiological YAP phosphatase. We found that PPM1A was associated with YAP/TAZ in both the cytoplasm and the nucleus to directly eliminate phospho-S127 on YAP, which conferring YAP the nuclear distribution and transcription potency. Accordingly, genetic ablation or depletion of PPM1A in cells, organoids, and mice elicited an enhanced YAP/TAZ cytoplasmic retention and resulted in the diminished cell proliferation, severe gut regeneration defects in colitis, and impeded liver regeneration upon injury. These regeneration defects in murine model were largely rescued via a genetic large tumor suppressor kinase 1 (LATS1) deficiency or the pharmacological inhibition of Hippo-YAP signaling. Therefore, we identify a physiological phosphatase of YAP/TAZ, describe its critical effects in YAP/TAZ cellular distribution, and demonstrate its physiological roles in mammalian organ regeneration.

Sb4O5I2: Enhancing Birefringence through Optimization of Sb/I Ratio for Alignment of Stereochemically Active Lone Pairs.

Birefringent crystals are the key components of functional optics, contributing significantly to scientific and technological advancements. To enhance birefringence, the presence of stereochemically active lone pairs offers a unique opportunity. In fact, strengthening the stereochemical activity and aligning uniformly lone pairs face tough challenges. Herein, an anisotropic layered crystal, Sb4O5I2, is discovered to exhibit enhanced birefringence. The influence of crystal symmetry on the birefringence of Sb4O5X2 (X = Cl, Br, or I) is found to be minor. Instead, the asymmetric nature of ABUCBs (i.e., cis-X3[SbO3]6- and cis-X3[SbO4]8-) plays a crucial role in enhancing the optical anisotropy. And the orientation of these ABUCBs is equally important. We demonstrate that by adjusting the Sb/I ratio from 5:1 to 2:1, all of the intralayer Sb atoms in Sb5O7I-P63 are forced onto the surface position. This structural adjustment leads to strengthened ionic bonding interactions, enhanced activity of the lone pairs, and uniform alignments of the ABUCBs in Sb4O5I2. Consequently, this results in a 6-fold increase in birefringence.

Novel Fluorinated Anion Exchange Membranes Based on Poly(Pentafluorophenyl-Carbazole) with High Ionic Conductivity and Alkaline Stability for Fuel Cell Applications.

Constructing good microphase separation structures by designing different polymer backbones and ion-conducting groups is an effective strategy for improving the ionic conductivity and chemical stability of anion exchange membranes (AEMs). In this study, a series of AEMs based on the poly(pentafluorophenylcarbazole) backbone grafted with different cationic groups are designed and prepared to construct well-defined microphase separation morphology and improve the trade-off between the properties of AEMs. Highly hydrophobic fluorinated backbone and alkyl spaces enhance phase separation and construct interconnected hydrophilic channels for anion transport. The ionic conductivity of the PC-PF-QA membrane is 123 mS cm-1 at 80 °C, and the ionic conductivity of the PC-PF-QA membrane decreased by only 6% after 960 h of immersion at 60 °C in 1 M NaOH aqueous solution. The maximum peak power density of the single cell based on PC-PF-QA is 214 mW cm-2 at 60 °C.

Analysis of the Effects of Evidence-Based Nursing Interventions on Promoting Functional Recovery in Neurology and General Surgery Intensive Care Patients.

Objective: The study aimed to examine how evidence-based nursing contributes to enhancing recovery among patients in the neurology and general surgery departments of intensive care units. Methods: A retrospective analysis was conducted on clinical data of 97 neurology and general surgery patients of Xi'shan People's Hospital in Wuxi, China, who were assigned to control group (n=48, received standard nursing interventions) and observation group (n=48, received evidence-based nursing interventions). The outcomes include treatment compliance, recovery, psychological status, self-perception, and nursing satisfaction. Results: In the observation group, treatment compliance significantly surpassed the control group (97.73% vs. 80.95%, P < .05). Post-intervention, the observation group exhibited lower National Institutes of Health Stroke Scale (NIHSS) scores and higher Barthel scores than controls, showed improved SAS and SDS, and had shorter mobilization time and hospital stay compared to controls (all P < .05). Conclusion: Compared to traditional approaches, evidence-based interventions enhance treatment compliance, self-perception, reduce negative emotions, and facilitate recovery.

Anisotropic structure building unit involving diverse chemical bonds: a new opportunity for high-performance second-order NLO materials.

We define the anisotropic structure building unit that encompasses diverse chemical bonds (ABUCB). The ABUCB is highly likely to cause anisotropy in both crystallographic structure and spatial electron distribution, ultimately resulting in enhanced macroscopic optical anisotropy. Accordingly, the (PO3F)2- or (SO3F)- tetrahedron involving the unique P-F or S-F bond serves as such an ABUCB. The distinct chemical bond effectively alters the microscopic nature of the structure building unit, such as polarizability anisotropy, hyperpolarizability, and geometry distortion; this consequently changes the macroscopic second-order nonlinear optical (2nd-NLO) properties of the materials. In this review, we summarize both typical and newly emerged compounds containing ABUCBs. These compounds encompass approximately 90 examples representing six distinct categories, including phosphates, borates, sulfates, silicates, chalcogenides and oxyhalides. Furthermore, we demonstrate that the presence of ABUCBs in DUV/UV NLO compounds contributes to an increase in birefringence and retention of a large band gap, facilitating phase matching in high-energy short-wavelength spectral ranges. On the other hand, the inclusion of ABUCBs in IR NLO compounds offers a feasible method for increasing the band gap and consequently enhancing the larger laser-induced damage threshold. This review consolidates various trial-and-error explorations and presents a novel strategy for designing 2nd-NLO compounds, potentially offering an opportunity for the development of high-performance 2nd-NLO materials.

Remarkable Second Harmonic Generation Response in (C5H6NO)+(CH3SO3)-: Unraveling the Role of Hydrogen Bond in Thermal Driven Nonlinear Optical Switch.

Heat-activated second harmonic generation (SHG) switching materials are gaining interest for their ability to switch between SHG on and off states, offering potential in optoelectronic applications. The novel nonlinear optical (NLO) switch, (C5H6NO)+(CH3SO3)- (4-hydroxypyridinium methylsulfonate, 4HPMS), is a near-room-temperature thermal driven material with a strong SHG response (3.3 × KDP), making it one of the most potent heat-stimulated NLO switches. It offers excellent contrast of 13 and a high laser-induced damage threshold (2.5 × KDP), with reversibility > 5 cycles. At 73 °C, 4HPMS transitions from the noncentrosymmetric Pna21 room temperature phase (RTP) to the centrosymmetric P21/c phase, caused by the rotation of the (C5H6NO)+ and (CH3SO3)- due to partially thermal breaking of intermolecular hydrogen bonds. The reverse phase change exhibits a large 50 °C thermal hysteresis. Density functional theory (DFT) calculations show that (C5H6NO)+ primarily dictates both the SHG coefficient (dij) and birefringence (∆n(Zeiss) = 0.216 vs ∆n(cal.) = 0.202 at 546 nm; Δn(Immersion) = 0.210 vs ∆n(cal.) = 0.198 at 589.3 nm), while the band gap (Eg) is influenced synergistically by (C5H6NO)+ and (CH3SO3)-. Additionally, 4HPMS-RTP also exhibits mechanochromism upon grinding as well as an aggregation-enhanced emission in a mixture of acetone and water.

Overdamped Phonon Diffusion and Nontrivial Electronic Structure Leading to a High Thermoelectric Figure of Merit in KCu5Se3.

Thermoelectric copper selenides are highly attractive owing to not only their constituent nontoxic, abundant elements but also their ultralow liquid-like lattice thermal conductivity (κlat). For the first time, the promising thermoelectric properties of the new KCu5Se3 are reported herein, showing a high power factor (PF = 9.0 µWcm-1 K-2) and an intrinsically ultralow κlat = 0.48 Wm-1 K-1. The doped K1-xBaxCu5Se3 (x = 0.03) realizes a figure-of-merit ZT = 1.3 at 950 K. The crystallographic structure of KCu5Se3 allows complex lattice dynamics that obey a rare dual-phonon transport model well describing a high scattering rate and an extremely short phonon lifetime that are attributed to interband phonon tunneling, confinement of the transverse acoustic branches, and temperature-dependent anharmonic renormalization, all of which generate an unprecedently high contribution of the diffusive phonons (70% at 300 K). The overall weak chemical bonding feature of KCu5Se3 gives K+ cations a quiescence behavior that further blocks the heat flux transfer. In addition, the valence band edge energy dispersion of KCu5Se3 is quasilinear that allows a large Seebeck coefficient even at high hole concentrations. These in-depth understandings of the ultralow lattice thermal conductivity provide new insights into the property-oriented design and synthesis of advanced complex chalcogenide materials.

Temperature Effects on Electrochemical Energy-Storage Materials: A Case Study of Yttrium Niobate Porous Microspheres.

Lithium-ion batteries (LIBs) are very popular electrochemical energy-storage devices. However, their applications in extreme environments are hindered because their low- and high-temperature electrochemical performance is currently unsatisfactory. In order to build all-climate LIBs, it is highly desirable to fully understand the underlying temperature effects on electrode materials. Here, based on a novel porous-microspherical yttrium niobate (Y0.5 Nb24.5 O62 ) model material, this work demonstrates that the operation temperature plays vital roles in electrolyte decomposition on electrode-material surfaces, electrochemical kinetics, and crystal-structure evolution. When the operation temperature increases, the reaction between the electrolyte and the electrode material become more intensive, causing the formation of thicker solid electrolyte interface (SEI) films, which decreases the initial Coulombic efficiency. Meanwhile, the electrochemical kinetics becomes faster, leading to the larger reversible capacity, higher rate capability, and more suitable working potential (i.e., lower working potential for anodes and higher working potential for cathodes). Additionally, the maximum unit-cell-volume change becomes larger, resulting in poorer cyclic stability. The insight gains here can provide a universal guide for the exploration of all-climate electrode materials and their modification methods.

Stress Response in the Honeybee (Apis mellifera L.) Gut Induced by Chlorinated Paraffins at Residue Levels Found in Bee Products.

Chlorinated paraffins (CPs) have become global pollutants and are of considerable concern as a result of their persistence and long-distance transmission in the environment and toxicity to mammals. However, their risks to pollinating insects are unknown. Honeybees are classical pollinators and sensitive indicators of environmental pollution. Herein, the effects of CPs on the gut microenvironment and underlying mechanisms were evaluated and explored using Apis mellifera L. Both short- and medium-chain CPs had significant sublethal effects on honeybees at a residue dose of 10 mg/L detected in bee products but did not significantly alter the composition or diversity of the gut microbiota. However, this concentration did induce significant immune, detoxification, and antioxidation responses and metabolic imbalances in the midgut. The mechanisms of CP toxicity in bees are complicated by the complex composition of these chemicals, but this study indicated that CPs could substantially affect intestinal physiology and metabolic homeostasis. Therefore, CPs in the environment could have long-lasting impacts on bee health. Future studies are encouraged to identify novel bioindicators of CP exposure to detect early contamination and uncover the detailed mechanisms underlying the adverse effects of CPs on living organisms, especially pollinating insects.

Up-regulation of CREB-1 regulates tendon adhesion in the injury tendon healing through the CREB-1/TGF-ß3 signaling pathway.

AIM: To explore the mechanism of the healing of tendon tissue and anti-adhesion, and to discuss the role of the transforming growth factor-ß3 (TGF-ß3)/cAMP response element binding protein-1 (CREB-1) signaling pathway in the healing process of tendons. METHOD: All mice were divided into four groups of 1, 2, 4, and 8 weeks respectively. Each time group was divided into four treatment groups: the amplification group, the inhibition group, the negative group, and the control group. When the tendon injury model was established, the CREB-1 virus was injected into the tendon injury parts. A series of methods such as gait behaviourism, anatomy, histological examination, immunohistochemical examination and collagen staining were employed to assess the tendon healing and the protein expression of TGF-ß3, CREB-1, Smad3/7 and type I/III collagen (COL-I/III). CREB-1 virus was sent to tendon stem cells to assess the protein expression of TGF-ß1, TGF-ß3, CREB-1, COL-I/III by methods such as immunohistochemistry and Western blot. RESULTS: The amplification group showed better gait behaviourism than the inhibition group in the healing process. The amplification group also had less adhesion than the negative group. Hematoxylin-eosin (HE) staining of tendon tissue sections showed that the number of fibroblasts in the amplification group was less than the inhibition group, and the immunohistochemical results indicated that the expression of TGF-ß3, CREB-1, and Smad7 at each time point was higher than the inhibition group. The expression of COL-I/III and Smad3 in the amplification group was lower than the inhibition group at all time points. The collagen staining indicated that the ratio of type I/III collagen in the amplification group was higher than the negative group at 2,4,8 week. The CREB-1 amplification virus could promote the protein expression of TGF-ß3, CREB-1 and inhibit the protein expression of TGF-ß1 and COL-I/III in the tendon stem cells. CONCLUSION: In the process of tendon injury healing, CREB-1 could promote the secretion of TGF-ß3, so as to promote the tendon healing and have the effect of anti-adhesion in tendons. It might provide new intervention targets for anti-adhesion treatment of tendon injuries.

Exploring RNA methylation as a promising biomarker for assessing sublethal effects of fipronil on honeybees (Apis mellifera L.).

Honeybees play a crucial role as pollinators for crops and are regarded as sensitive bioindicators of environmental health. The widespread use of pesticides poses a severe threat to honeybee survival. However, there is limited information available on the specific risks associated with fipronil exposure in honeybees, particularly concerning the impact on RNA methylation throughout their lifespan. This study aimed to evaluate the effects of sublethal concentrations of fipronil on RNA m6A and m5C methylations, along with the associated genes in honeybee larvae and newly emerged adults. LC-MS/MS analysis revealed a notable hypomethylation of m5C in larvae, while hypermethylation of m6A was observed in the adult brain. Significant changes in the expression of genes such as AmWTAP, AmYTHDF, AmALKBH4, AmALKBH6, AmALKBH8, AmNSUN5, AmNOP2, AmTET1, and AmYBX1 were observed in the adult brain, whereas alterations in the expression of AmNSUN2, AmMETTL14, AmALKBH1, AmALKBH4, AmALKBH6 AmALYREF, AmTET1, and AmYBX1 were observed in the larvae. Notably, the expression of AmALKBH1 was not detected in any fipronil-treated larvae, suggesting its potential as an early risk indicator for honeybee larvae in future assessments. This pioneering study provides insights into the effects of fipronil on RNA methylations in honeybees and explores the possibility of employing RNA methylation as a tool for assessing pesticide risks in this important pollinator species. These findings offer new perspectives on honeybee protection and the development of toxicity evaluation systems for pesticides.

First report of Neopestalotiopsis rosae causing leaf blight on Shatangju in southern China.

Shatangju (Citrus reticulata Blanco cv. Shatangju) belongs to genus Citrus and was cultivated extensively in southern China. In April 2022, a leaf blight-like symptom (firstly brown spots appeared on infecting leaves, then these brown spots extended, finally the whole leaves displayed blight-like symptom) was observed on 5%~10% of Shatangju seedlings (around five hundreds in total) in an orchard located in Wuhan city, Hubei, China. Diseased leaves from three seedlings were collected and cut into pieces (0.2 to 0.5 cm). These pieces were surface-sterilized using 75% ethanol for 3 min, rinsed with sterile distilled water for several times, then placed on potato dextrose agar (PDA) and incubated at 26°C with 12-h light/dark cycle. Over 20 pieces plated, wherein 30% were identified as Colletotrichum fructicola, 60% as Neopestalotiopsis spp., and 10% developed saprophytes. C. fructicola was a known pathogen on citrus, thus Neopestalotiopsis spp. was further investigated. Eight single-conidium colonies of the Neopestalotiopsis spp. were obtained, wherein STJ-8 was chosen as a representative for further study. The average growth rate of STJ-8 was 15.1±0.5 mm/day (n=5). Fungal colonies produced white cottony mycelium with abundant black acervuli distributed in concentric rings 6-8 days after planting, which ranged from 342.3 to 710.5 µm in diameter (n=100). Conidia were fusoid, five cells, four septa with average dimensions of 25.36×5.47 µm (n=100). Basal and apical cells were hyaline, wherein three middle cells were brown with darker septa. The apical cell was cylindrical with two to three transparent accessory filaments (13.7 to 30.5 µm in length, n=80). Basal cell was conic with an appendage (4.1 to 8.8 µm in length, n=40). Partial sequences of internal transcribed spacer (ITS), translation elongation factor 1-alpha (TEF-1α), and ß-tubulin (TUB2) were amplified with reported primers (White et al. 1990; Lee et al. 2006; Maharachchikumbura et al. 2014), sequenced, and submitted to GenBank (accession nos. ITS: OP236541; TEF-1α: OP250124; TUB2:OP263094). BLASTn results showed 100% identity with the corresponding sequences of Neopestalotiopsis rosae. A multilocus phylogenetic analysis showed STJ-8 was closest to N. rosae. Thus, STJ-8 was identified as N. rosae. Pathogenicity tests were performed on one-year-old Shatangju seedlings and detached primary leaves by inoculating needle-wounded leaves with seven days old 5-mm mycelial plugs/acervuli (about 5000 spores) of STJ-8. Control seedlings/leaves were inoculated with 5-mm PDA plugs/sterile water drops. All inoculated detached leaves were cultured at same the place with STJ-8 cultured, while inoculated seedlings were put in a growth chamber at 26°C under a 16-h light/dark cycle (60% humidity). Symptoms developed on all inoculated leaves (except healthy control) 2 and 4 days post-inoculation by mycelial plugs and acervuli, respectively. N. rosae was re-isolated from the inoculated leaves, confirming Koch's postulates. N. rosae has been reported to cause diseases on various plants worldwide (Rebollar-Alviter et al. 2020; Xavier et al. 2021; Lawrence et al. 2022). In China, N. rosae has been reported to cause leaf spot/blight on pecan and strawberry (Wu et al. 2021; Gao et al. 2022), which caused great loss on these crops. To our knowledge, this is the first report of N. rosae causing leaf disease on citrus. Our study is important for developing control strategies against N. rosae in future.

Comparisons of Different Bearing Surfaces in Cementless Total Hip Arthroplasty: A Systematic Review and Bayesian Network Analysis.

BACKGROUND: We aimed to make comparisons of different bearing surfaces in patients after cementless total hip arthroplasty. METHODS: The network meta-analysis was guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. The primary outcomes were implant survival and Harris hip score (HHS). Secondary outcomes included linear wear rates and serum level of metal ions. Subgroup analyses were performed by: (1) classifying head sizes as small and large; (2) femoral heads as ceramic and metal; and (3) liners as metal, ceramic, polyethylene, highly cross-linked polyethylene (HXP), or vitamin E-infused highly cross-linked polyethylene (HXPE). A total of 64 eligible RCTs with different bearings were assessed. Overall inconsistency and heterogeneity were acceptable. RESULTS: In the 10 years follow-up, metal-on-polythene and ceramic-on-polythene bearings with small heads showed higher risk for revisions compared with metal-on-HXP and ceramic-on-HXP bearings with small heads. Similarly, only metal or ceramic-on-polythene bearings with small heads showed inferiority in HHS compared with other bearings. Conventional polyethylene liners showed higher linear wear rates compared with HXP, HXPE, and ceramic liners at 5 and 10 years after surgery, while metal-on-metal and ceramic-on-metal bearings showed higher serum level of cobalt and chromium. CONCLUSION: Bearings containing HXP, HXPE, and ceramic liners showed comparable survivorship and hip function at follow-up of 5 and 10 years. Hard-on-hard bearings containing metal had higher serum level of metal ions than others. Bearings containing conventional polyethylene had worse performance in terms of implant survival, hip function, and wear rates. LEVEL OF EVIDENCE: Level I.

Poria cocos (Schw.) Wolf, a Traditional Chinese Edible Medicinal Herb, Promotes Neuronal Differentiation, and the Morphological Maturation of Newborn Neurons in Neural Stem/Progenitor Cells.

Neurogenesis in the adult brain comprises the entire set of events of neuronal development. It begins with the division of precursor cells to form a mature, integrated, and functioning neuronal network. Adult neurogenesis is believed to play an important role in animals' cognitive abilities, including learning and memory. In the present study, significant neuronal differentiation-promoting activity of 80% (v/v) ethanol extract of P. cocos (EEPC) was found in Neuro-2a cells and mouse cortical neural stem/progenitor cells (NSPCs). Subsequently, a total of 97 compounds in EEPC were identified by UHPLC-Q-Exactive-MS/MS. Among them, four major compounds-Adenosine; Choline; Ethyl palmitoleate; and L-(-)-arabinitol-were further studied for their neuronal differentiation-promoting activity. Of which, choline has the most significant neuronal differentiation-promoting activity, indicating that choline, as the main bioactive compound in P. cocos, may have a positive effect on learning and memory functions. Compared with similar research literature, this is the first time that the neuronal differentiation-promoting effects of P. cocos extract have been studied.

α-Dicarbonyl compounds in food products: Comprehensively understanding their occurrence, analysis, and control.

α-Dicarbonyl compounds (α-DCs) are readily produced during the heating and storage of foods, mainly through the Maillard reaction, caramelization, lipid-peroxidation, and enzymatic reaction. They contribute to both the organoleptic properties (i.e., aroma, taste, and color) and deterioration of foods and are potential indicators of food quality. α-DCs are also important precursors to hazardous substances, such as acrylamide, furan, advanced lipoxidation end products, and advanced glycation end products, which are genotoxic, neurotoxic, and linked to several diseases. Recent studies have indicated that dietary α-DCs can elevate plasma α-DC levels and lead to "dicarbonyl stress." To accurately assess their health risks, quantifying α-DCs in food products is crucial. Considering their low volatility, inability to absorb ultraviolet light, and high reactivity, the analysis of α-DCs in complex food systems is a challenge. In this review, we comprehensively cover the development of scientific approaches, from extraction, enrichment, and derivatization, to sophisticated detection techniques, which are necessary for quantifying α-DCs in different foods. Exposure to α-DCs is inevitable because they exist in most foods. Recently, novel strategies for reducing α-DC levels in foods have become a hot research topic. These strategies include the use of new processing technologies, formula modification, and supplementation with α-DC scavengers (e.g., phenolic compounds). For each strategy, it is important to consider the potential mechanisms underlying the formation and removal of process contaminants. Future studies are needed to develop techniques to control α-DC formation during food processing, and standardized approaches are needed to quantify and compare α-DCs in different foods.