Evaluation of the effectiveness and safety of sequential vaccination with inactivated SARS-CoV-2 vaccine and Ad5-nCoV booster in pediatric liver transplant recipients.

Amidst the COVID-19 pandemic, uncertainty persists among caregivers regarding the vaccination of pediatric liver transplant recipients (PLTRs). This study evaluates the immunogenicity and safety of COVID-19 vaccination in this vulnerable population. A cohort of 30 PLTRs underwent sequential vaccinations with an inactivated SARS-CoV-2 vaccine followed by an Ad5-nCoV booster. We collected and analyzed blood samples pre-vaccination and four weeks post-vaccination to quantify antibody and IGRA (IFN-γ Release Assay) levels. We also documented any adverse reactions occurring within seven days post-vaccination and monitored participants for infections over six months post-vaccination, culminating in a comprehensive statistical analysis. The Ad5-nCoV booster substantially elevated IgG (T1: 18.01, 20%; T2: 66.61, 55%) and nAb (T1: 119.29, 8%; T2: 3799.75, 80%) levels, as well as T-cell responses, in comparison to the initial dose. The first dose was associated with some common adverse reactions, such as injection site pain (13.3%) and fever (16.6%), but a low rate of systemic reactions (16.0%). There was no significant difference in Omicron infection rates or RTPCR conversion times between vaccinated and unvaccinated groups. Notably, following Omicron infection, vaccinated individuals exhibited significantly higher SARS-CoV-2 IgG and nAb titers (average IgG: 231.21 vs. 62.09 S/CO, p = 0.0003; nAb: 5246.11 vs. 2592.07 IU/mL, p = 0.0002). The use of inactivated vaccines followed by an Ad5-nCoV booster in PLTRs is generally safe and elicits a robust humoral response, albeit with limited T-cell responses.

The major histocompatibility complex participates in Parkinson's disease.

Parkinson's disease (PD) is a common neurodegenerative disease characterized by progressive loss of dopaminergic neurons in the substantia nigra and the aggregation of alpha-synuclein (α-syn). The central nervous system (CNS) has previously been considered as an immune-privileged area. However, studies have shown that the immune responses are involved in PD. The major histocompatibility complex (MHC) presents antigens from antigen-presenting cells (APCs) to T lymphocytes, immune responses will be induced. MHCs are expressed in microglia, astrocytes, and dopaminergic neurons. Single nucleotide polymorphisms in MHC are related to the risk of PD. The aggregated α-syn triggers the expression of MHCs by activating glia cells. CD4+ and CD8+ T lymphocytes responses and microglia activation are detected in brains of PD patients. In addiction immune responses further increase blood-brain barrier (BBB) permeability and T cell infiltration in PD. Thus, MHCs are involved in PD through participating in immune and inflammatory responses.

Novel superhard semiconducting structures of C8B2N2 predicted using the first-principles approach.

Using first-principles calculations, we predicted three novel superhard semiconducting structures of C8B2N2 with a space group of P3m1. We investigated their mechanical properties and electronic structures up to 100 GPa. These three structures were successfully derived by substituting carbon (C) atoms with isoelectronic boron (B) and nitrogen (N) atoms in the P3m1 phase, which is the most stable structure of BCN and exhibits exceptional mechanical properties. Our results indicated that these structures had superior energy over previously reported t-C8B2N2, achieved by replacing C atoms in the diamond supercell with B and N atoms. To ensure their stable existence, we thoroughly examined their mechanical and dynamical stabilities, and we found that their hardness values reached 82.4, 83.1, and 82.0 GPa, which were considerably higher than that of t-C8B2N2 and even surpassing the hardness of c-BN. Calculations of the electron localization function revealed that the stronger carbon-carbon covalent bonds made them much harder than t-C8B2N2. Additionally, our further calculations of band structures revealed that these materials had indirect bandgaps of 4.164, 4.692, and 3.582 eV. These findings suggest that these materials have the potential to be used as superhard semiconductors, potentially surpassing conventional superhard materials.

Study of high-pressure thermophysical properties of orthocarbonate Sr3CO5 using deep learning molecular dynamics simulations.

The exploration of the physical attributes of the recently discovered orthocarbonate Sr3CO5 is significant for comprehending the carbon cycle and storage mechanisms within the Earth's interior. In this study, first-principles calculations are initially used to examine the structural phase transitions of Sr3CO5 polymorphs within the range of lower mantle pressures. The results suggest that Sr3CO5 with the Cmcm phase exhibits a minimal enthalpy between 8.3 and 30.3 GPa. As the pressure exceeds 30.3 GPa, the Cmcm phase undergoes a transition to the I4/mcm phase, while the experimentally observed Pnma phase remains metastable under our studied pressure. Furthermore, the structural data of SrO, SrCO3, and Sr3CO5 polymorphs are utilized to develop a deep learning potential model suitable for the Sr-C-O system, and the pressure-volume relationship and elastic constants calculated using the potential model are in line with the available results. Subsequently, the elastic properties of Cmcm and I4/mcm phases in Sr3CO5 at high temperature and pressure are calculated using the molecular dynamics method. The results indicate that the I4/mcm phase exhibits higher temperature sensitivity in terms of elastic moduli and wave velocities compared to the Cmcm phase. Finally, the thermodynamic properties of the Cmcm and I4/mcm phases are predicted in the range of 0-2000 K and 10-120 GPa, revealing that the heat capacity and bulk thermal expansion coefficient of both phases increase with temperature, with the constant volume heat capacity gradually approaching the Dulong-Petit limit as the temperature rises.

The association between air pollutant exposure and cerebral small vessel disease imaging markers with modifying effects of PRS-defined genetic susceptibility.

Studies have highlighted a possible link between air pollution and cerebral small vessel disease (CSVD) imaging markers. However, the exact association and effects of polygenic risk score (PRS) defined genetic susceptibility remains unclear. This cross-sectional study used data from the UK Biobank. Participants aged 40-69 years were recruited between the year 2006 and 2010. The annual average concentrations of NOX, NO2, PM2.5, PM2.5-10, PM2.5 absorbance, and PM10, were estimated, and joint exposure to multiple air pollutants was reflected in the air pollution index (APEX). Air pollutant exposure was classified into the low (T1), intermediate (T2), and high (T3) tertiles. Three CSVD markers were used: white matter hyper-intensity (WMH), mean diffusivity (MD), and fractional anisotropy (FA). The first principal components of the MD and FA measures in the 48 white matter tracts were analysed. The sample consisted of 44,470 participants from the UK Biobank. The median (T1-T3) concentrations of pollutants were as follows: NO2, 25.5 (22.4-28.7) µg/m3; NOx, 41.3 (36.2-46.7) µg/m3; PM10, 15.9 (15.4-16.4) µg/m3; PM2.5, 9.9 (9.5-10.3) µg/m3; PM2.5 absorbance, 1.1 (1.0-1.2) per metre; and PM2.5-10, 6.1 (5.9-6.3) µg/m3. Compared with the low group, the high group's APEX, NOX, and PM2.5 levels were associated with increased WMH volumes, and the estimates (95 %CI) were 0.024 (0.003, 0.044), 0.030 (0.010, 0.050), and 0.032 (0.011, 0.053), respectively, after adjusting for potential confounders. APEX, PM10, PM2.5 absorbance, and PM2.5-10 exposure in the high group were associated with increased FA values compared to that in the low group. Sex-specific analyses revealed associations only in females. Regarding the combined associations of air pollutant exposure and PRS-defined genetic susceptibility with CSVD markers, the associations of NO2, NOX, PM2.5, and PM2.5-10 with WMH were more profound in females with low PRS-defined genetic susceptibility, and the associations of PM10, PM2.5, and PM2.5 absorbance with FA were more profound in females with higher PRS-defined genetic susceptibility. Our study demonstrated that air pollutant exposure may be associated with CSVD imaging markers, with females being more susceptible, and that PRS-defined genetic susceptibility may modify the associations of air pollutants.

Identification of circular dorsal ruffles as signal platforms for the AKT pathway in glomerular podocytes.

Circular dorsal ruffles (CDRs) are rounded membrane ruffles induced by growth factors to function as precursors of the large-scale endocytosis called macropinocytosis. In addition to their role in cellular uptake, recent research using cell line systems has shown that CDRs/macropinocytosis regulate the canonical AKT-mTORC1 growth factor signaling pathway. However, as CDRs have not been observed in tissues, their physiological relevance has remained unclear. Here, utilizing ultrahigh-resolution scanning electron microscopy, we first report that CDRs are expressed in glomerular podocytes ex vivo and in vivo, and we visually captured the transformation process to macropinocytosis. Moreover, through biochemical and imaging analyses, we show that AKT phosphorylation localized to CDRs upstream of mTORC1 activation in podocyte cell lines and isolated glomeruli. These results demonstrate the physiological role of CDRs as signal platforms for the AKT-mTORC1 pathway in glomerular podocytes at the tissue level. As mTORC1 plays critical roles in podocyte metabolism, and aberrant activation of mTORC1 triggers podocytopathies, our results strongly suggest that targeting CDR formation could represent a potential therapeutic approach for these diseases.

Pharmacological suppression of NLRP3 inflammasome attenuated the development of autoimmune thyroiditis.

Autoimmune thyroiditis (AIT), characterized by an endless inflammatory process of self-destruction, ultimately leads to chronic swelling of the thyroid gland and its dysfunction. Here, we investigated the involvement of the NLR pyrin domain-containing 3 (NLRP3) inflammasome in AIT development. We found that NLRP3 is significantly upregulated in the thyroid of AIT patients and mice with experimental autoimmune thyroiditis (EAT). Pharmacological suppression of NLRP3 using its inhibitor MCC950 suppressed the progression of EAT in vivo. Furthermore, MCC950 treatment significantly reduced the numbers of infiltrating CD4+ and CD8+ T cells in the thyroid. Moreover, MCC950 significantly lowered the amounts of T helper 1 cells, T helper 17 cells, interferon gamma, and interleukin-17A; however, it significantly increased regulatory-T-cell numbers and interleukin-10 levels. These results suggest that suppression of NLRP3 inflammasome activation reverses AIT by inhibiting Th1- and Th17-cell responses and promoting Treg cell responses. Hence, the NLRP3 inflammasome is a promising therapeutic and theragnostic target in AIT. inhibits Th1- and Th17-cell responses and promotes Treg cell responses.

Associations between maternal urinary isoflavone concentrations and anogenital distance of offspring throughout infancy: a prospective cohort study.

STUDY QUESTION: Are maternal urinary isoflavone (ISO) concentrations during pregnancy associated with anogenital distance (AGD) in infants at birth, and at 6 and 12 months of age? SUMMARY ANSWER: Higher maternal urinary ISO concentrations during pregnancy were associated with longer AGD in infants of both sexes, and equol (EQU) and daidzein (DAD) were identified as the important ISO mixture components in the observed associations. WHAT IS KNOWN ALREADY: Evidence of the association of prenatal exposure to ISO with offspring's AGD is mainly derived from animal studies, which used different study designs and had inconsistent results. Only one human study has been reported and it found null associations between maternal ISO exposure during pregnancy and AGD among boys at birth, with a small sample size and a wide range of exposure windows. No human study on girls was found. STUDY DESIGN, SIZE, DURATION: Prospective cohort study (Shanghai-Minhang Birth Cohort Study), with pregnant women recruited at 12-16 weeks of gestation in Shanghai, China between April and December 2012. One thousand two hundred and twenty-five live singletons were left in the cohort at delivery of which 480 mother-infant pairs had data on both maternal urinary ISO concentrations and at least one AGD measurement and were included in the present study. Anopenile distance (AGDAP) and anoscrotal distance (AGDAS) of boys and anoclitoral distance (AGDAC) and anofourchette distance (AGDAF) of girls were measured at birth and at 6 and 12 months of age. PARTICIPANTS/MATERIALS, SETTING, METHODS: Multiple linear regression models were used to examine the associations between maternal ISO concentrations and AGD. Bayesian kernel machine regression (BKMR) was implemented to examine both the overall effects of ISO mixture and the single effect of each ISO and identify important components of ISO mixture. MAIN RESULTS AND THE ROLE OF CHANCE: A general profile of higher concentrations of maternal ISO associated with longer AGD in infants of both sexes was observed, when maternal education, parity, BMI before pregnancy (BMI, categorical variable), passive smoking during early pregnancy, age at delivery, gestational weeks and infant body size were adjusted for. Among boys, EQU was associated with increased AGDAS at birth and at 6 and 12 months, and DAD was associated with increased AGDAP at birth. Among girls, the associations of EQU and DAD with increased AGDAC and AGDAF at birth were found. When gestational weight gain and feeding patterns of infants in the first 6 months were additionally adjusted for, and maternal BMI was adjusted for as a continuous variable, more pronounced associations were observed, especially for associations of genistein (GEN), DAD and glycitein (GLY) with increased AGDAP and AGDAS at 6 months in boys. However, these associations were not always observed in the highest tertile group, and no consistent dose-response relationships were found. Similar results were observed in BKMR models, showing positive correlations of concentration of ISO mixture with increased AGDAS at both 6 and 12 months among boys, and increased AGDAC and AGDAF at birth among girls. Statistically significant increments of 4.96 mm (95% credible interval (CrI): 1.40, 8.52) and 1.07 mm (95% CrI: 0.02, 2.13) in AGDAS at 6 months among boys and AGDAC at birth among girls, respectively, were observed at the 75th percentile of ISO mixture, compared with 25th percentile. EQU and DAD were identified as the important components among ISO-AGD associations. LIMITATIONS, REASONS FOR CAUTION: First, due to the short half-lives of ISO, the accuracy of a single spot urine sample reflecting ISO exposure during pregnancy may be limited, and thus may cause non-differential misclassification. Second, despite the adjustments for several important covariates in the study, unmeasured and residual confounding factors may remain a concern. Third, false discovery due to multiple testing may remain. Finally, the reduced sample sizes attributed to the loss of follow-up and missing data of confounders may limit our ability to detect an association, if any existed. WIDER IMPLICATIONS OF THE FINDINGS: Prenatal ISO exposure may affect the reproductive development of offspring. As ISO can be widely detected in pregnant women, especially in Eastern countries, more studies are warranted to provide evidence of the effects of prenatal ISO exposure on long-term reproductive outcomes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the National Key Research and Development Program of China (2021YFC2701003), the National Natural Science Foundation of China (22076123), the Science and Technology Commission of Shanghai Municipality (21ZR1454700 and 20ZR1448000), the Shanghai Municipal Health Commission (20194Y0160) and Innovation-oriented Science and Technology Grant from NHC Key Laboratory of Reproduction Regulation (CX2022-04). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Lactate and Lactylation in the Brain: Current Progress and Perspectives.

As the final product of glycolysis, lactate features not only as an energy substrate, a metabolite, and a signaling molecule in a variety of diseases-such as cancer, inflammation, and sepsis-but also as a regulator of protein lactylation; this is a newly proposed epigenetic modification that is considered to be crucial for energy metabolism and signaling in brain tissues under both physiological and pathological conditions. In this review, evidence on lactylation from studies on lactate metabolism and disease has been summarized, revealing the function of lactate and its receptors in the regulation of brain function and summarizing the levels of lactylation expression in various brain diseases. Finally, the function of lactate and lactylation in the brain and the potential mechanisms of intervention in brain diseases are presented and discussed, providing optimal perspectives for future research on the role of lactylation in the brain.

MDM2-mediated ubiquitination of LKB1 contributes to the development of diabetic cataract.

Diabetic cataract (DC) is a common complication of diabetes mellitus. The epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is a crucial event in the development of DC. Murine double minute 2 (MDM2) is an E3 ubiquitin ligase that promotes EMT by regulating diverse targets. However, little is known about how MDM2 is involved in the pathogenesis of DC. We found the mRNA and protein levels of MDM2 were up-regulated in the lens of DC patients and rats. Thus, high glucose (HG)-induced human lens epithelial cells (HLECs) were constructed for further investigation. The results showed that the level of MDM2 was increased in HG-cultured HLECs, and the MDM2 knockdown alleviated HG-induced abnormal migration, EMT, and oxidative stress damage. Moreover, co-immunoprecipitation and ubiquitination assays demonstrated that MDM2 down-regulated LKB1 expression by ubiquitination degradation. LKB1 was found to be lower expressed in human and rat DC lenses, and HG-stimulated HLECs. Also, LKB1 overexpression mitigated HG-induced dysfunction of HLECs. Finally, our data showed that the changes related to EMT and oxidative stress induced by MDM2 knockdown were restored by down-regulation of LKB1. Together, MDM2 may involve in the pathogenesis of DC through down-regulating LKB1. MDM2 might be an effective therapeutical target of DC.

Environmentally relevant concentrations of organic (benzophenone-3) and inorganic (titanium dioxide nanoparticles) UV filters co-exposure induced neurodevelopmental toxicity in zebrafish.

UV filters, widely used in personal care products, are ubiquitous environmental pollutants detected and pose a significant public health concern. Benzophenone-3 (BP3) and titanium dioxide nanoparticles (nano-TiO2) are the predominant organic and inorganic UV filters in environmental media. However, few studies have explored the combined developmental neurotoxic (DNT) effects and the underlying mechanisms when co-exposed to BP3 and nano-TiO2. In the present study, zebrafish (Danio rerio) embryos were exposed to environmentally relevant concentrations of BP3 (10 µg/L), nano-TiO2 (100 µg/L), and mixtures starting from 6 h post fertilization (hpf), respectively. Developmental indicators and motor behaviors were investigated at various developmental stages. Our results showed that BP3 alone or co-exposed with nano-TiO2 increased spontaneous movement at 24 hpf, co-exposure decreased touch response at 30 hpf and hatching rate at 60 hpf. Consistent with these motor deficits, co-exposure to BP3 and nano-TiO2 inhibited relative axon length of primary motor neuron during the early developmental stages, disturbed the expression of axonal growth-related genes at 30 and 48 hpf, increased cell apoptosis on the head region and mRNA levels of apoptosis-related genes, and also increased reactive oxygen species (ROS) levels in zebrafish, suggesting the functional relevance of structural changes. Taken together, our findings demonstrated that BP3 alone or in combination with nano-TiO2 at environmentally relevant concentrations induced evident neurotoxic effects on the developing embryos in zebrafish.

Prenatal exposure to ambient PM2.5 and its chemical constituents and child intelligence quotient at 6 years of age.

There are limited studies on the associations between prenatal exposure to constituents of fine particulate matter (PM2.5) and children's intelligence quotient (IQ). Our study aimed to explore the associations between prenatal PM2.5 and its six constituents and the IQ levels of 6-year-old children. We included 512 mother-child pairs. We used a satellite-based modelling framework to estimate prenatal PM2.5 and its six constituents (ammonium, sulfate, nitrate, organic carbon, soil dust, and black carbon). We assessed the children's IQ using the short form of the Wechsler Intelligence Scale. Perceptual Reasoning Index (PRI), Verbal Comprehension Index (VCI), and Full Scale IQ (FSIQ) scores were computed. The multiple informant model (MIM) was applied to explore the trimester specific effects of PM2.5 and its six constituents' exposure on children's PRI, VCI, and FSIQ. To examine whether the duration of breastfeeding and physical activity (PA) could modify the effects of PM2.5 on children's IQ, we stratified the analyses according to the duration of breastfeeding (≤6 and >6 months) and time of outdoor activities after school (≤2 and >2 h/week). The first trimester PM2.5 and its five constituents' exposures were inversely associated with FSIQ [ß = -1.34, 95 % confidence interval [CI] (-2.71, 0.04) for PM2.5] and PRI [ß = -2.18, 95 %CI (-3.80, -0.57) for PM2.5] in children. The associations were magnified among boys and those with less outdoor activities or shorter breastfeeding duration. Our results indicate that prenatal PM2.5 and several of its main constituents' exposure may disrupt cognitive development in children aged 6 years. More PA and longer breastfeeding duration may alleviate the detrimental effects of prenatal PM2.5 exposure on children's cognitive function.

Gap balance difference of unicompartmental knee arthroplasty between hanging leg and supine leg position: a prospective cohort study.

PURPOSE: Gap balance is critical in Oxford unicompartmental knee arthroplasty (OUKA) surgery; the effect of lower limb positioning on gap balance judgements has not been reported. There are two mean operative positions for OUKA patients, the hanging leg (HL) and the supine leg (SL) position. This study aimed to investigate the gap balance achieved by current UKA surgical techniques by using a force sensor, to compare the differences in gap balance between the two different positions, and to test whether the difference in gap balance leads to different outcomes in terms of component alignment and early post-operative clinical outcomes. METHODS: This prospective study included 97 knees (76 patients), who underwent OUKA from June 1, 2020, to July 31, 2021, of which 67 knees underwent UKA in the supine leg position and the other 30 in the hanging leg position. When the operator was satisfied with the gap balance, the contact forces between the trial and the spacer block were measured at 90° of knee flexion (flexion gap) and 20° of knee flexion (extension gap) using a pre-developed matrix flexible force sensor. X-rays were reviewed three to five days after surgery. Knee Society Scores (KSS) were obtained at the six month follow-up. RESULTS: Compared to the HL group, the contact force at the flexion gap was higher in the SL group: 55.15N (SD 43.36N) vs. 34.25N (SD 27.56N) (p < 0.05), whereas in the extension gap, there was no significant difference, 90.19 N (SD 43.36N) in the SL group and 86.72N (SD 43.08N) in the HL group (ns.). The contact force was greater in the extension gap than in the flexion gap in both groups (p < 0.01). The gap balance difference in the HL group was 52.46N (SD 31.33N), which was greater than that of the SL group at 35.03N (SD 19.50N) (p < 0.05). There were no significant differences in component alignment or lower limb mechanical alignment between the two groups. There was no significant difference in pre-operative and post-operative KSS between the two groups, while post-operative KSS was significantly higher in both groups compared to the pre-operative period. CONCLUSION: The intra-operative contact forces between the flexion and extension gaps differed in the two groups; the hanging leg position appeared to produce a greater difference in the judgement of gap balance than the supine leg position, but this difference did not adversely affect the alignment of the component or the early post-operative clinical outcome.

Recent Advances in Nanoparticle-Mediated Co-Delivery System: A Promising Strategy in Medical and Agricultural Field.

Drug and gene delivery systems mediated by nanoparticles have been widely studied for life science in the past decade. The application of nano-delivery systems can dramatically improve the stability and delivery efficiency of carried ingredients, overcoming the defects of administration routes in cancer therapy, and possibly maintaining the sustainability of agricultural systems. However, delivery of a drug or gene alone sometimes cannot achieve a satisfactory effect. The nanoparticle-mediated co-delivery system can load multiple drugs and genes simultaneously, and improve the effectiveness of each component, thus amplifying efficacy and exhibiting synergistic effects in cancer therapy and pest management. The co-delivery system has been widely reported in the medical field, and studies on its application in the agricultural field have recently begun to emerge. In this progress report, we summarize recent progress in the preparation and application of drug and gene co-delivery systems and discuss the remaining challenges and future perspectives in the design and fabrication.

Development and validation of a nomogram for predicting pulmonary infections after Intracerebral hemorrhage in elderly people.

OBJECTIVES: The purpose of this study was to develop and validate a nomogram for the prediction of pulmonary infections in elderly patients with intracerebral hemorrhage (ICH) during hospitalization in the intensive care unit (ICU). METHODS: A total of 1183 elderly patients diagnosed with ICH were included from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and randomly grouped into training (n=831) and validation (n=352) cohorts. Candidate predictors were identified using the least absolute shrinkage and selection operator (LASSO) regression. Meanwhile, the variables derived from the LASSO regression were included in the multivariate logistic regression analysis, the variables with P < 0.05 were included in the final model and the nomogram was constructed. The discriminatory ability was assessed by plotting the receiver operating curve (ROC) and calculating the area under the curve (AUC). The Performance of the model was assessed by calibration plots and the Hosmer-Lemeshow goodness-of-fit test (HL test). In addition, clinical decision curves assess the net clinical benefit. RESULTS: The nomogram included chronic lung disease, dysphagia, mechanical ventilation, use of antibiotics, Glasgow Coma Scale (GCS), Logical Organ Dysfunction System (LODS), blood oxygen saturation (SpO2), white blood cell count (WBC) and prothrombin time (PT). The AUC of the predictive model was 0.905 (95 % CI: 0.877, 0.764) in the training cohort and 0.888 (95 % CI: 0.754, 0.838) in the validation cohort, which showed satisfactory discriminative ability. Second, the nomogram showed good calibration. Decision curve analysis showed that the predictive nomogram was clinically useful. CONCLUSION: A prediction model for predicting pulmonary infections in elderly ICH patients was constructed. The model can help clinicians to identify high-risk patients as soon as possible and prevent the occurrence of pulmonary infections.

Coronal tibiofemoral subluxation under valgus stress force radiography is useful for evaluating postoperative coronal tibiofemoral subluxation in mobile-bearing UKA.

PURPOSE: Coronal tibiofemoral subluxation (CTFS) is considered a controversial and potential contraindication to unicompartmental knee arthroplasty (UKA) but is less discussed. The study aims to observe the CTFS in a cohort of patients before and after mobile-bearing UKA and to investigate the relationship between preoperative variables (preoperative CTFS and preoperative CTFS under valgus stress) and postoperative CTFS after mobile-bearing UKA. METHODS: The study retrospectively analyzed 181 patients (224 knees) undergoing mobile-bearing UKA from September 1 2019 to December 31 2021. By using hip-to-ankle anterior-posterior (AP) standing radiographs and valgus stress force radiographs, preoperative CTFS, preoperative CTFS under valgus stress, and postoperative CTFS were measured. CTFS was defined as the distance between the tangent line to the outermost joint edge of the lateral condyle of the femur and the tangent line of the lateral tibial plateau. All patients were divided into two groups based on postoperative CTFS, group A (postoperative CTFS ≤ 5 mm) and group B (postoperative CTFS > 5 mm). The Student's t-test, one-way ANOVA together with Tukey's post hoc test, the chi-square test, the Fisher's exact test, Pearson correlation analysis, simple and multiple linear regression, and univariate and multiple logistic regression were used in the analyses. RESULTS: The means ± standard deviations (SD) of preoperative CTFS, preoperative CTFS under valgus stress, and postoperative CTFS were 4.96 ± 1.82 mm, 3.06 ± 1.37 mm, and 3.19 ± 1.27 mm. The difference between preoperative CTFS and postoperative CTFS was statistically significant (p < 0.001). The preoperative CTFS (6.35 ± 1.34 mm) in Group B (n = 22) was significantly higher than that (4.81 ± 1.82 mm) in Group A (n = 202) (p < 0.001), so was the variable-preoperative CTFS under valgus stress (5.41 ± 1.00 mm (Group B) > 2.80 ± 1.14 mm (Group A), p < 0.001). In Pearson correlation analysis, there was a correlation between preoperative CTFS and postoperative CTFS (r = 0.493, p < 0.001), while the correlation between preoperative CTFS under valgus stress and postoperative CTFS was stronger (r = 0.842, p < 0.001). In multiple linear regression analysis, preoperative CTFS under valgus stress (ß = 0.798, 95% confidence interval (CI) = 0.714-0.883, p < 0.001) was significantly correlated with postoperative CTFS. In multiple logistic regression analysis, preoperative CTFS under valgus stress (OR = 12.412, 95% CI = 4.757-32.384, and p < 0.001) was expressed as the risk factor of postoperative CTFS (> 5 mm). CONCLUSION: Preoperative CTFS can be improved significantly after mobile-bearing UKA. In addition, postoperative CTFS is correlated with preoperative CTFS under valgus stress and a higher preoperative CTFS under valgus stress will increase the risk of higher postoperative CTFS (> 5 mm). LEVEL OF EVIDENCE: Level III.

Bioconjugation via Hetero-Selective Clamping of Two Different Amines with ortho-Phthalaldehyde.

Amino groups are common in both natural and synthetic compounds and offer a very attractive class of endogenous handles for bioconjugation. However, the ability to differentiate two types of amino groups and join them with high hetero-selectivity and efficiency in a complex setting remains elusive. Herein, we report a new method for bioconjugation via one-pot chemoselective clamping of two different amine nucleophiles using a simple ortho-phthalaldehyde (OPA) reagent. Various α-amino acids, aryl amines, and secondary amines can be crosslinked to the ϵ-amino side chain of lysine on peptides or proteins with high efficiency and hetero-selectivity. This method offers a simple and powerful means to crosslink small molecule drugs, imaging probes, peptides, proteins, carbohydrates, and even virus particles without any pre-functionalization.

Enhanced performance of an AlGaN-based deep ultraviolet light-emitting diode using a p+-GaN/SiO2/ITO tunnel junction.

In this work, a 280-nm-wavelength deep-ultraviolet light-emitting diode (DUV LED) with a p+-GaN/SiO2/ITO tunnel junction is fabricated and investigated. Due to the decreased tunnel region width and enhanced electric field intensity in the 1-nm-thick SiO2 layer, the interband tunneling efficiency and the corresponding hole injection efficiency are promoted. Therefore, the external quantum efficiency (EQE) for the proposed device is increased when compared with a traditional DUV LED. In addition, an improved current spreading effect is observed for our proposed device. As a result, improved wall-plug efficiency (WPE) is obtained owing to the increased optical power and decreased forward operating voltage. Meanwhile, the enhanced electric field intensity in the SiO2 layer reduces the voltage drop in the p-n junction region for the proposed device, and thus the leakage current is reduced.

Circular dorsal ruffles disturb the growth factor-induced PI3K-AKT pathway in hepatocellular carcinoma Hep3B cells.

BACKGROUND: Circular dorsal ruffles (CDRs) are rounded membrane ruffles induced on the dorsal surfaces of cells stimulated by growth factors (GF). They can serve as signal platforms to activate AKT protein kinase. After GF stimulation, phosphatidylinositol 3-kinase (PI3K) generates phosphatidylinositol (3,4,5)-triphosphate (PIP3) in the plasma membrane. PIP3 accumulates inside CDRs, recruits AKT into the structures, and phosphorylates them (pAKT). Given the importance of the PI3K-AKT pathway in GF signaling, CDRs are likely involved in cell growth. Interestingly, some cancer cell lines express CDRs. We hypothesized that CDRs contribute to carcinogenesis by modulating the AKT pathway. In the present study, we identified CDR-expressing cancer cell lines and investigated their cellular functions. METHODS: CDR formation was examined in six cancer cell lines in response to epidermal growth factor (EGF) and insulin. The morphology of the CDRs was characterized, and the related signaling molecules were observed using confocal and scanning electron microscopy. The role of CDRs in the AKT pathway was studied using biochemical analysis. The actin inhibitor cytochalasin D (Cyto D) and the PI3K inhibitor TGX221 were used to block CDRs. RESULTS: GF treatment induced CDRs in the hepatocellular carcinoma (HCC) Hep3B cell line, but not in others, including HCC cell lines HepG2 and Huh7, and the LO2 hepatocyte cell line. Confocal microscopy and western blot analysis showed that the PI3K-PIP3-AKT pathway was activated at the CDRs and that receptor proteins were recruited to the structures. Cyto D and TGX221 completely blocked CDRs and partially attenuated GF-induced pAKT. These results indicate that CDRs regulate the receptor-mediated PI3K-AKT pathway in Hep3B cells and the existence of CDR-independent pAKT mechanisms. CONCLUSIONS: Our results showed that CDRs modulate the AKT pathway in Hep3B cells. Since CDRs were not observed in other HCC and hepatocyte cell lines, we propose that CDRs in Hep3B would determine the carcinoma characteristic of the cell by aberrantly triggering the AKT pathway. Signaling molecules involved in CDR formation are promising therapeutic targets for some types of HCC. Video abstract.

An Investigation of 2D Spine Magnetic Resonance Imaging (MRI) with Compressed Sensing (CS).

OBJECTIVE: To investigate the feasibility of compressed sensing MRI (CS-MRI) in the application of 2D spinal imaging and compare its performance with conventional MR imaging (non-CS-MRI). METHODS: The CS imaging protocol was optimized on 5 volunteers. Non-CS-MRI and CS-MRI of 2D sagittal T1 weighted imaging (WI), Sag T2WI, and axial T2WI were performed for 71 patients (22 cervical, 8 thoracic, 41 lumbar MRI). Paired t tests were conducted to compare the total scan time. Three radiologists assessed image quality and lesion diagnosis independently. A Kendall W test was performed to assess interobserver agreement of the image quality scores and lesion diagnosis between readers. A nonparametric test (Wilcoxon test) was performed to compare the image quality. For lesion diagnosis, the interobserver and interstudy agreements were evaluated by kappa analysis. Paired t tests were conducted for SNR and CNR comparison. RESULTS: The mean scan time for spine CS-MRI (4 min 28.7 s ± 34.6 s) was significantly shorter than that with non-CS-MRI (7 min 21.3 s ± 38.7 s, t = - 47.464, P < 0.0001). CS-MRI achieved higher SNR and CNR than Non-CS-MRI in image quality assessment. Interobserver agreements of lesion diagnosis were excellent between non-CS-MRI and CS-MRI (kappa value from 0.913 to 1.000, P < 0.001). Interstudy agreements of lesion assessments were also excellent (kappa value = 1.000, with P < 0.001). CONCLUSION: CS-MRI spine imaging can significantly reduce the scan time, while maintaining comparable imaging quality to non-CS-MRI.