Crosstalk of methylglyoxal and calcium signaling in maize (Zea mays L.) thermotolerance through methylglyoxal-scavenging system.

Methylglyoxal (MG) and calcium ion (Ca2+) can increase multiple-stress tolerance including plant thermotolerance. However, whether crosstalk of MG and Ca2+ exists in the formation of maize thermotolerance and underlying mechanism still remain elusive. In this paper, maize seedlings were irrigated with MG and calcium chloride alone or in combination, and then exposed to heat stress (HS). The results manifested that, compared with the survival percentage (SP, 45.3%) of the control seedlings, the SP of MG and Ca2+ alone or in combination was increased to 72.4%, 74.2%, and 83.4% under HS conditions, indicating that Ca2+ and MG alone or in combination could upraise seedling thermotolerance. Also, the MG-upraised SP was separately weakened to 42.2%, 40.3%, 52.1%, and 39.4% by Ca2+ chelator (ethylene glycol tetraacetic acid, EGTA), plasma membrane Ca2+ channel blocker (lanthanum chloride, LaCl3), intracellular Ca2+ channel blocker (neomycin, NEC), and calmodulin (CaM) antagonist (trifluoperazine, TFP). However, significant effect of MG scavengers N-acetylcysteine (NAC) and aminoguanidine (AG) on Ca2+-induced thermotolerance was not observed. Similarly, an endogenous Ca2+ level in seedlings was increased by exogenous MG under non-HS and HS conditions, while exogenous Ca2+ had no significant effect on endogenous MG. These data implied that Ca2+ signaling, at least partly, mediated MG-upraised thermotolerance in maize seedlings. Moreover, the activity and gene expression of glyoxalase system (glyoxalase I, glyoxalase II, and glyoxalase III) and non-glyoxalase system (MG reductase, aldehyde reductase, aldo-keto reductase, and lactate dehydrogenase) were up-regulated to a certain extent by Ca2+ and MG alone in seedlings under non-HS and HS conditions. The up-regulated MG-scavenging system by MG was enhanced by Ca2+, while impaired by EGTA, LaCl3, NEC, or TFP. These data suggest that the crosstalk of MG and Ca2+ signaling in maize thermotolerance through MG-scavenging system. These findings provided a theoretical basis for breeding climate-resilient maize crop and developing smart agriculture.

[Analysis of Spatial Distribution of Ecosystem Services and Driving Factors in Northeast China].

Northeast China is an important ecological barrier in China, and an in-depth understanding of the spatial distribution in ecosystem services （ESs）, and the driving factors is crucial for realizing the subsequent management and protection of ESs. In the study, we quantitatively assessed the characteristics of spatial distribution in ESs in Northeastern China using the InVEST, RWEQ, and RUSLE models and identified the driving factors of ESs spatial distribution in conjunction with the geodetector based on meteorological data, remote sensing data, and socio-economic data. The results showed that the spatial distribution of ESs in Northeast China had obvious spatial heterogeneity. The high values of habitat quality （HQ）, carbon sequestration （CS） services, and soil conservation （SC） services were mainly distributed in the northern part of the four eastern leagues of the Inner Mongolia Autonomous Region, the northern part of Heilongjiang Province, and the eastern part of Northeast China, which were high in fraction vegetation cover, and low values were mainly found in southwestern and eastern Heilongjiang Province, western Jilin Province, and western Liaoning Province. The high values of the water yield （WY） service and wind prevention and sand fixation （WPSF） service were distributed in the east of the Inner Mongolia Autonomous Region and the east of Liaoning Province. The high values of WY services and WPSF services were distributed in the eastern part of Northeast China and the four eastern provinces of the Inner Mongolia Autonomous Region. According to the geodetector results, slope had the strongest explanatory power for the spatial distribution of SC services with a q-value of 0.31, land use/cover change had the strongest explanatory power for the spatial distribution of HQ and CS services with q-values of 0.64 and 0.52, respectively, and fraction vegetation coverage and annual precipitation had the strongest explanatory power for the spatial distribution of WPSF and WY services with q-values of 0.24 and 0.64, respectively, and there were interactions among all the driving factors. The spatial distribution of ESs in Northeast China was mainly influenced by natural factors. The results will provide a scientific basis for subsequent management and enhancement of ESs in Northeast China.

Comparison of robotic or computer-assisted navigation versus fluoroscopic freehand techniques in the accuracy of posterior cervical screw placement during cervical spine surgery: a meta-analysis.

OBJECTIVE: Robot guidance (RG) and computer-assisted navigation (CAN) have been increasingly utilized for posterior cervical screw placement in cervical spine surgery, and cervical screw malposition may contribute to catastrophic complications. However, the superiority of the navigation using RG or CAN compared with conventional freehand (FH) techniques remains controversial, and no meta-analysis comparing the two methods in cervical spine surgery has been performed. METHODS: The PubMed, Embase, Web of Science, Cochrane, China National Knowledge Infrastructure, and Wanfang databases were searched for eligible literature. Studies reporting the primary outcomes of the accuracy of cervical screw placement using RG or CAN compared with FH techniques were included. Bias was evaluated using the Cochrane risk of bias criteria and the Newcastle-Ottawa Scale. The outcomes were evaluated in terms of odds ratio or standardized mean difference and corresponding 95% confidence interval. RESULTS: One randomized controlled trial and 18 comparative cohort studies published between 2012 and 2023 consisting of 946 patients and 4163 cervical screws were included in this meta-analysis. The RG and CAN techniques were associated with a substantially higher rate of optimal and clinically acceptable cervical screw accuracy than FH techniques. Furthermore, compared with the FH group, the navigation group showed fewer postoperative adverse events, less blood loss, shorter hospital lengths of stay, and lower postoperative Neck Disability Index scores. However, the navigation and FH groups had equivalent intraoperative times and postoperative visual analog scale and Japanese Orthopaedic Association scores at the final follow-up. CONCLUSIONS: Both RG and CAN are superior to FH techniques in terms of the accuracy of cervical screw placement. Navigation techniques, including RG and CAN methods, are accurate, safe, and feasible in cervical spine surgery.

Characteristics of psychrophilic bacterial communities and associated metabolism pathways in different environments by a metagenomic analysis.

Psychrophilic bacteria, the dominant spoilage organisms in raw milk, secrete heat-stable extracellular proteases and lipases that lead to the decomposition of milk and dairy products. In this study, we investigated psychrophilic bacteria in 165 raw milk samples collected across four seasons and six regions in China using shotgun metagenomic sequencing and traditional culture methods. The isolated psychrophilic bacteria were classified into 40 genera and 185 species. Pseudomonas was the most prevalent, accounting for 51.13 % of the genera, while Lactococcus and Chryseobacterium were also notably abundant (> 6.0 %). Metagenomic sequencing revealed that Pseudomonas (47.9 %), Stenotrophomonas (9.75 %), Sphingomonas (6.73 %), Latilactobacillus (6.38 %) and Lactococcus (5.16 %) were the dominant genera in the raw milk samples. The diversity of psychrophilic bacteria in raw milk was strongly influenced by seasonal variations, with the sampling region being a less significant factor. KEGG annotation indicated that carbohydrate and amino acid metabolism were the primary metabolic pathways in these bacteria. Metagenomic sequencing not only accurately identifies species but also provides functional insights into psychrophilic bacteria in raw milk, aiding in understanding their activities, promoting their control on farms, and ultimately improving raw milk quality.

Biomechanical changes of oblique lumbar interbody fusion with different fixation techniques in degenerative spondylolisthesis lumbar spine: a finite element analysis.

OBJECTIVE: There is a dearth of comprehensive research on the stability of the spinal biomechanical structure when combining Oblique Lumbar Interbody Fusion (OLIF) with internal fixation methods. Hence, we have devised this experiment to meticulously examine and analyze the biomechanical changes that arise from combining OLIF surgery with different internal fixation techniques in patients diagnosed with degenerative lumbar spondylolisthesis. METHODS: Seven validated finite element models were reconstructed based on computed tomography scan images of the L3-L5 segment. These models included the intact model, a stand-alone (S-A) OLIF model, a lateral screw rod (LSR) OLIF model, a bilateral pedicle screw (BPS) OLIF model, an unilateral pedicle screw (UPS) OLIF model, a bilateral CBT (BCBT) OLIF model, and an unilateral CBT(UCBT) OLIF model. The range of motion (ROM), as well as stress levels in the cage, L4 lower endplate, L5 upper endplate, and fixation constructs were assessed across these different model configurations. RESULTS: S-A model had the highest average ROM of six motion modes, followed by LSR, UPS, UCBT, BPS and BCBT. The BCBT model had a relatively lower cage stress than the others. The maximum peak von Mises stress of the fixation constructs was found in the LSR model. The maximum peak von Mises stress of L4 lower endplate was found in the S-A model. The peak von Mises stress on the L4 lower endplate of the rest surgical models showed no significant difference. The maximum peak von Mises stress of the L5 upper endplate was found in the S-A model. The minimum peak von Mises stress of the L5 upper endplate was found in the BCBT model. No significant difference was found for the peak von Mises stress of the L5 upper endplate among LSR, BPS, UPS and UCBT models. CONCLUSION: Among the six different fixation techniques, BCBT exhibited superior biomechanical stability and minimal stress on the cage-endplate interface. It was followed by BPS, UCBT, UPS, and LSR in terms of effectiveness. Conversely, S-A OLIF demonstrated the least stability and resulted in increased stress on both the cage and endplates. Combining OLIF with BCBT fixation technique enhanced biomechanical stability compared to BPS and presented as a less invasive alternative treatment for patients with degenerative lumbar spondylolisthesis.

Sepsis Biomarkers: Advancements and Clinical Applications-A Narrative Review.

Sepsis is now defined as a life-threatening syndrome of organ dysfunction triggered by a dysregulated host response to infection, posing significant challenges in critical care. The main objective of this review is to evaluate the potential of emerging biomarkers for early diagnosis and accurate prognosis in sepsis management, which are pivotal for enhancing patient outcomes. Despite advances in supportive care, traditional biomarkers like C-reactive protein and procalcitonin have limitations, and recent studies have identified novel biomarkers with increased sensitivity and specificity, including circular RNAs, HOXA distal transcript antisense RNA, microRNA-486-5p, protein C, triiodothyronine, and prokineticin 2. These emerging biomarkers hold promising potential for the early detection and prognostication of sepsis. They play a crucial role not only in diagnosis but also in guiding antibiotic therapy and evaluating treatment effectiveness. The introduction of point-of-care testing technologies has brought about a paradigm shift in biomarker application, enabling swift and real-time patient evaluation. Despite these advancements, challenges persist, notably concerning biomarker variability and the lack of standardized thresholds. This review summarizes the latest advancements in sepsis biomarker research, spotlighting the progress and clinical implications. It emphasizes the significance of multi-biomarker strategies and the feasibility of personalized medicine in sepsis management. Further verification of biomarkers on a large scale and their integration into clinical practice are advocated to maximize their efficacy in future sepsis treatment.

A Coupling-Induced Assembly Strategy for Constructing Artificial Shell on Mitochondria in Living Cells.

The strategy of in vivo self-assembly has been developed for improved enrichment and long-term retention of anticancer drug in tumor tissues. However, most self-assemblies with non-covalent bonding interactions are susceptible to complex physiological environments, leading to weak stability and loss of biological function. Here, we develop a coupling-induced assembly (CIA) strategy to generate covalently crosslinked nanofibers, which is applied for in situ constructing artificial shell on mitochondria. The oxidation-responsive peptide-porphyrin conjugate P1 is synthesized, which self-assemble into nanoparticles. Under the oxidative microenvironment of mitochondria, the coupling of thiols in P1 causes the formation of dimers, which is further ordered and stacked into crosslinked nanofibers. As a result, the artificial shell is constructed on the mitochondria efficiently through multivalent cooperative interactions due to the increased binding sites. Under ultrasound (US) irradiation, the porphyrin molecules in the shell produce a large amount of reactive oxygen species (ROS) that act on the adjacent mitochondrial membrane, exhibiting ~2-fold higher antitumor activity than nanoparticles in vitro and in vivo. Therefore, the mitochondria-targeted CIA strategy provides a novel perspective on improved sonodynamic therapy (SDT) and shows potential applications in antitumor therapies.

Electro-optically tunable optical delay on a lithium niobate photonic chip.

An approach for continuous tuning of on-chip optical delay with a microring resonator is proposed and demonstrated. By introducing an electro-optically tunable waveguide coupler, the bus waveguide to the resonance coupling can be effectively tuned from the under-coupling regime to the over-coupling regime. The optical delay is experimentally characterized by measuring the relative phase shift between lasers and shows a large dynamic range of delay from -600 to 600 ps and an efficient tuning of delay from -430 to -180 ps and from 40 to 240 ps by only a 5 V voltage.

Analysis of the Variation in Antioxidant Activity and Chemical Composition upon the Repeated Thermal Treatment of the By-Product of the Red Ginseng Manufacturing Process.

Steamed ginseng water (SGW) is a by-product of the repeated thermal processing of red ginseng, which is characterized by a high bioactive content, better skin care activity, and a large output. However, its value has been ignored, resulting in environmental pollution and resource waste. In this study, UHPLC-Q-Exactive-MS/MS liquid chromatography-mass spectrometry and multivariate statistical analysis were conducted to characterize the compositional features of the repeated thermal-treated SGW. The antioxidant activity (DPPH, ABTS, FRAP, and OH) and chemical composition (total sugars, total saponins, and reducing and non-reducing sugars) were comprehensively evaluated based on the entropy weighting method. Four comparison groups (groups 1 and 3, groups 1 and 5, groups 1 and 7, and groups 1 and 9) were screened for 37 important common difference markers using OPLS-DA analysis. The entropy weight method was used to analyze the weights of the indicators; the seventh SGW sample was reported to have a significant weight. The results of this study suggest that heat treatment time and frequency can be an important indicator value for the quality control of SGW cycling operations, which have great potential in antioxidant products.

Integrating Polyoxometalates and Silver Clusters into Atomically Precise Molecular Heterojunction.

The Ag cluster-POM assemblies have been shown to possess interesting and potentially useful properties. However, there is no precedent example of atomically precise Ag cluster-POM assemblies showing heterojunction effects in photocatalysis. Herein, the synthesis and total structure determination of the periodically distributed molecular heterojunction [Ag12(SCy)6(CH3CN)12(PW12O40)]n (Ag12-PW12) are reported. The assembly of Ag/W clusters into 3D network can endow the resulting binary structure with an aesthetic topology and unique physicochemical properties. More remarkably, the incorporation of Ag12 cluster with PW12 can efficiently facilitate the separation of photogenerated electrons and holes, thus significantly promoting the catalytic efficiency in selective oxidation of sulfides. The Ag12-PW12 heterojunction can be recovered and reused five times with no drastic change in the catalytic performance. This research is expected to assist in the rational design of cluster-based heterojunction catalysts. The increase of catalytic activity of the Ag12-PW12 assembly in comparison with the unassembled Ag12 and PW12 clusters is attributed to the synergistic effect of Ag12 and PW12 clusters, offering the splendid opportunity for deciphering structure-reactivity relationship of heterostructure-coupled photosystem.

Systolic blood pressure and early neurological deterioration in minor stroke: A post hoc analysis of ARAMIS trial.

BACKGROUND: Systolic blood pressure (SBP) was a predictor of early neurological deterioration (END) in stroke. We performed a secondary analysis of ARAMIS trial to investigate whether baseline SBP affects the effect of dual antiplatelet versus intravenous alteplase on END. METHODS: This post hoc analysis included patients in the as-treated analysis set. According to SBP at admission, patients were divided into SBP ≥140 mmHg and SBP <140 mmHg subgroups. In each subgroup, patients were further classified into dual antiplatelet and intravenous alteplase treatment groups based on study drug actually received. Primary outcome was END, defined as an increase of ≥2 in the NIHSS score from baseline within 24 h. We investigated effect of dual antiplatelet vs intravenous alteplase on END in SBP subgroups and their interaction effect with subgroups. RESULTS: A total of 723 patients from as-treated analysis set were included: 344 were assigned into dual antiplatelet group and 379 into intravenous alteplase group. For primary outcome, there was more treatment effect of dual antiplatelet in SBP ≥140 mmHg subgroup (adjusted RD, -5.2%; 95% CI, -8.2% to -2.3%; p < 0.001) and no effect in SBP <140 mmHg subgroup (adjusted RD, -0.1%; 95% CI, -8.0% to 7.7%; p = 0.97), but no significant interaction between subgroups was found (adjusted p = 0.20). CONCLUSIONS: Among patients with minor nondisabling acute ischemic stroke, dual antiplatelet may be better than alteplase with respect to preventing END within 24 h when baseline SBP ≥140 mmHg.

Research progress of acupuncture and moxibustion for the enhanced synergism of chemotherapy. / é’ˆç¸ååŒåŒ–ç–—å®žçŽ°å¢žæ•ˆçš„ç ”ç©¶è¿›å±•.

The application of acupuncture and moxibustion in alleviating the adverse effects of chemotherapy drugs has been widely recognized at home and abroad, but the studies have been rarely summarized for the enhanced anti-tumor effect and its mechanism of acupuncture and moxibustion to synergize the chemotherapy drugs. This paper reviewed the clinical and basic studies on the synergism of chemotherapy with acupuncture and moxibustion in recent years. It was found that chemotherapy synergized with acupuncture and moxibustion can suppress cancer to a certain extent and improve the quality of life in patients. The effect mechanism of acupuncture and moxibustion combined with chemotherapy drugs is related to promoting tumor cell apoptosis, improving the immune and vascular microenvironment, and advancing chemotherapy drug enrichment on the affected area. It provides the evidences and ideas for enhancing the effect of chemotherapy by delivering acupuncture and moxibustion as an adjuvant therapy.

Design and radiological confirmation of 3-column cortical bone trajectory in the lumbar spine.

OBJECTIVE: The aim of this study was to design a novel lumbar cortical bone trajectory (CBT) penetrating the anterior, middle, and posterior vertebral area using imaging; measure the relevant parameters to find theoretical parameters and screw placement possibilities; and investigate the optimal implantation trajectory of the CBT in patients with osteoporosis. METHODS: Three types of CBTs with appropriate lengths were selected to simulate screw placement using Mimics software. These CBTs were classified as the leading tip of the trajectory pointing to the posterior quarter area (original CBT [CBT-O]) and middle (novel CBT A [CBT-A]) and anterior quarter (novel CBT B [CBT-B]) of the superior endplate. The authors then measured the maximum screw diameter (MSD) and length (MSL), cephalad (CA) and lateral (LA) angles, and bone mineral density (Hounsfield unit [HU] values) of the planned novel 3-column CBT screw placements. The differences in the parameters of the novel CBTs, the percentages of successfully planned CBT screws, and the factors that influenced the successful planning of 3-column CBT screws were analyzed. RESULTS: Three-column CBT screws were successfully designed in all segments of the lumbar spine. The success rate of the 3-column CBT planned screws was 72.25% (83.25% for CBT-A and 61.25% for CBT-B). From the CBT-O type, to the CBT-A type, to the CBT-B type, the LA, CA, and MSD of the novel CBT screws decreased with increasing trajectory length. The HU values of the three types of trajectories were all significantly higher than that of the traditional pedicle screw trajectory (p < 0.001). The main factor affecting successful planning of the 3-column CBT screw was pedicle width. CONCLUSIONS: Moderating adjustment of the original screw parameters by reducing LAs and CAs to penetrate the anterior, middle, and posterior columns of the vertebral body using the 3-column CBT screw is feasible, especially in the lower lumbar spine.

Omics analysis revealed the intestinal toxicity induced by aflatoxin B1 and aflatoxin M1.

Aflatoxin B1 (AFB1), a common mycotoxin, can occur in agricultural products. As a metabolite of AFB1, aflatoxin M1 (AFM1) mainly exist in dairy products. These two mycotoxins threaten human health, although it is unclear how they affect the function of the intestinal barrier. In this study, mice were exposed to AFB1 (0.3 mg/kg body b.w.) and AFM1(3.0 mg/kg b.w.) either individually or in combination for 28 days to explore the main differentially expressed proteins (DEPs) and the associated enriched pathways. These findings were preliminarily verified by the transcriptomic and proteomic analyses in differentiated Caco-2 cells. The results revealed that AFB1 and AFM1 exposure in mice disrupted the function of the intestinal barrier, and the combined toxicity was greater than that of each toxin alone. Further proteomic analysis in mice demonstrated that the mechanisms underlying these differences could be explained as follows: (i) lipid metabolism was enriched by AFB1-induced DEPs. (ii) protein export pathway was stimulated by AFM1-induced DEPs. (iii) cell metabolic ability was inhibited (as evidenced by changes in UDP-GT1, UDP-GT2, and Gatm6), apoptosis was induced (MAP4K3), and epithelial cell integrity was disrupted (Claudin7 and IQGAP2), resulting in more extensive intestinal damage after combined treatment. In conclusion, the hazardous impact of co-exposure to AFB1 and AFM1 from proteomic perspectives was demonstrated in the present study.

Bispecific fibrous glue synergistically boosts vascular normalization and antitumor immunity for advanced renal carcinoma therapy.

Immune checkpoint blockade therapy represented by programmed cell death ligand 1 (PD-L1) inhibitor for advanced renal carcinoma with an objective response rate (ORR) in patients is less than 20%. It is attributed to abundant tumoral vasculature with abnormal structure limiting effector T cell infiltration and drug penetration. We propose a bispecific fibrous glue (BFG) to regulate tumor immune and vascular microenvironments simultaneously. The bispecific precursor glue peptide-1 (pre-GP1) can penetrate tumor tissue deeply and self-assemble into BFG in the presence of neuropilin-1 (NRP-1) and PD-L1. The resultant fibrous glue is capable of normalizing tumoral vasculature as well as restricting immune escape. The pre-GP1 retains a 6-fold higher penetration depth than that of antibody in the multicellular spheroids (MCSs) model. It also shows remarkable tumor growth inhibition (TGI) from 19% to 61% in a murine advanced large tumor model compared to the clinical combination therapy. In addition, in the orthotopic renal tumor preclinical model, the lung metastatic nodules are reduced by 64% compared to the clinically used combination. This pre-GP1 provides a promising strategy to control the progression and metastasis of advanced renal carcinoma.

[Characteristics of vegetation and soil in Caragana korshinskii plantations in the hilly and sandy areas of northwestern Shanxi Province, China]. / æ™‹è¥¿åŒ—ä¸˜é™µé£Žæ²™åŒºæŸ æ¡é”¦é¸¡å„¿äººå·¥æž—æ¤è¢«å’ŒåœŸå£¤éšæž—é¾„å˜åŒ–ç‰¹å¾.

We investigated the changes of soil nutrients and plant communities in the artificial sand fixation forests of Caragana korshinskii with different ages. The results showed that soil organic carbon and soil total nitrogen contents increased with the stand ages, and were significantly higher in 40 and 50 year-old than other ages. Soil organic carbon and total nitrogen contents recovered much faster in the surface layer (0-10 cm) than in others. Soil nutrient stoichiometric ratios (C:P, N:P) in the 0-10 cm soil layer differed significantly among different stand ages. With the increases of stand age, C and N contents in C. korshinskii leaves increased significantly, and reached the maximum at 50 year-old. Leaf P content increased first and then decreased, being maximum at 18 year-old. Leaf C:N first increased and then decreased, being maximum at 12 year-old. The contents of photosynthetic pigments and leaf C:P and N:P decreased first and then increased, being minimum at 18 year-old. C. korshinskii was mainly influenced by N availability before 40 year-old, but mainly limited by P after. The species number, density, and vegetation cover of annual and perennial herbaceous plants increased with stand ages, and the community shifted from a simple shrub plant community to a complex shrub-herb community. The biomass of C. korshinskii and herbaceous plants increased significantly with stand age, and had a significant positive correlation with the contents of soil organic carbon, total nitrogen and N:P.

Numerical analysis of on-chip acousto-optic modulators for visible wavelengths.

On-chip acousto-optic modulators that operate at an optical wavelength of 780 nm and a microwave frequency of 6.835 GHz are proposed. The modulators are based on a lithium-niobate-on-sapphire platform and efficiently excite surface acoustic waves and exhibit strong interactions with tightly confined optical modes in waveguides. In particular, a high-efficiency phase modulator and single-sideband mode converter are designed. We found that for both microwave and optical wavelengths below 1 µm, the interactions at the cross-sections of photonic waveguides are sensitive to the waveguide width and are significantly different from those in previous studies. Our designed devices have small footprints and high efficiencies, making them suitable for controlling rubidium atoms and realizing hybrid photonic-atomic chips. Furthermore, our devices have the potential to extend the acousto-optic modulators to other visible wavelengths for other atom transitions and for visible light applications, including imaging and sensing.

Bone metastases in oral squamous cell carcinoma: A real-world retrospective study based on the SEER database.

BACKGROUND: Bone metastases are rare in oral squamous cell carcinoma (OSCC). It has not been defined on the risk and prognosis of OSCC patients with bone metastases. The purpose of this study was to assess the factors associated with the development and prognosis of bone metastases among OSCC patients. METHODS: Demographic and clinicopathological characteristics of OSCC patients diagnosed between 2010 and 2019 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. To explore risk factors for developing bone metastases and prognosis, the univariate and multivariate logistic and Cox regression analysis were performed, further the predictive nomogram models were constructed. RESULTS: The incidence rate of bone metastases in newly diagnosed OSCC patients was 0.91 % (95 %CI 0.81% -1.02 %). Ultimately, 137 OSCC patients with bone metastases and 19,469 OSCC patients without bone metastases were included in the present study. Pathological grade, primary site, T/N stage and distant organ metastases (liver/lung/brain) were independently associated with the risk of developing bone metastases among OSCC patients. The C-index of a constructed risk-predicting nomogram was 0.86 (95 %CI 0.83-0.89). Multivariate Cox regression analysis indicated that lung metastases, the use of surgery as well as chemotherapy were three independent prognostic factors. The C-indexes of constructed risk-predicting nomograms were 0.70 (95 %CI 0.65-0.75), 0.68 (95 %CI 0.63-0.73) for OS and CSS, respectively. Calibration plots demonstrated an agreementbetween the established nomogram's predicted survival and actual survival. In addition, decision curve analysis (DCA) indicated these established nomograms had considerable net benefits and clinical utilities. CONCLUSION: This study defined the risk and prognostic factors for bone metastases among OSCC patients and the established nomograms were well calibrated for discrimination to predict bone metastasis development and prognosis.

Autophagy in Multiple Sclerosis: Phagocytosis and Autophagy of Oligodendrocyte Precursor Cells.

Multiple sclerosis (MS) is a leading cause of chronic neurological dysfunction in young to middle-aged adults, affecting approximately 2.5 million people worldwide. It is characterized by inflammation, multifocal demyelination, axonal loss, and white and gray matter gliosis. Autophagy is a highly conserved protein degradation pathway. Polymorphisms in autophagy-related genes have been implicated in a variety of autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, psoriasis and MS. However, the significance of autophagy in MS remains to be elucidated. This paper aims to explore the potential role of autophagy-related genes in MS diseases by using bioinformatics combined with machine learning methods. Finally, we obtained 9 autophagy genes with the highest correlation with MS, and further changes in these autophagy genes were verified in the experimental autoimmune encephalomyelitis (EAE) model and oligodendrocyte precursor cells (OPCs) engulfed myelin debris (MD). Combined with bioinformatic analysis and experimental data, Becn1 showed obvious expression abnormalities suggesting that this gene has vital functions in autophagy and MD engulfed by OPCs. This work will be of great significance for the further exploration of autophagy-related genes in demyelinating diseases.

Microinjection With Nanoparticles to Deliver Drugs in Prenatal Lung Explants - A Pilot Study for Prenatal Therapy in Congenital Diaphragmatic Hernia.

BACKGROUND: Fetoscopic endoluminal tracheal occlusion (FETO) improves the survival rate in fetuses with severe congenital diaphragmatic hernia (CDH). We hypothesize that prenatal therapies into the trachea during FETO can further improve outcomes. Here, we present an ex vivo microinjection technique with rat lung explants to study prenatal therapy with nanoparticles. METHODS: We used microsurgery to isolate lungs from rats on embryonic day 18. We injected chitosan nanoparticles loaded with fluorescein (FITC) into the trachea of the lung explants. We compared the difference in biodistribution of two types of nanoparticles, functionalized IgG-conjugated nanoparticles (IgG-nanoparticles) and bare nanoparticles after 24 h culture with immunofluorescence (IF). We used IF to mark lung epithelial cells with E-cadherin and to investigate an apoptosis (Active-caspase 3) and inflammatory marker (Interleukin, IL-6) and compared its abundance between the two experimental groups and control lung explants. RESULTS: We detected the presence of nanoparticles in the lung explants, and the relative number of nanoparticles to cells was 2.49 fold higher in IgG-nanoparticles than bare nanoparticles (p < 0.001). Active caspase-3 protein abundance was similar in the control, bare nanoparticles (1.20 fold higher), and IgG-nanoparticles (1.34 fold higher) groups (p = 0.34). Similarly, IL-6 protein abundance was not different in the control, bare nanoparticles (1.13 fold higher), and IgG-nanoparticles (1.12 fold higher) groups (p = 0.33). CONCLUSIONS: Functionalized nanoparticles had a higher presence in lung cells and this did not result in more apoptosis or inflammation. Our proof-of-principle study will guide future research with therapies to improve lung development prenatally. LEVELS OF EVIDENCE: N/A TYPE OF STUDY: Animal and laboratory study.