Cortical atrophy in early-stage patients with anti-NMDA receptor encephalitis: a machine-learning MRI study with various feature extraction.

Conventional brain magnetic resonance imaging (MRI) of anti-N-methyl-D-aspartate-receptor encephalitis (NMDARE) is non-specific, thus showing little differential diagnostic value, especially for MRI-negative patients. To characterize patterns of structural alterations and facilitate the diagnosis of MRI-negative NMDARE patients, we build two support vector machine models (NMDARE versus healthy controls [HC] model and NMDARE versus viral encephalitis [VE] model) based on radiomics features extracted from brain MRI. A total of 109 MRI-negative NMDARE patients in the acute phase, 108 HCs and 84 acute MRI-negative VE cases were included for training. Another 29 NMDARE patients, 28 HCs and 26 VE cases were included for validation. Eighty features discriminated NMDARE patients from HCs, with area under the receiver operating characteristic curve (AUC) of 0.963 in validation set. NMDARE patients presented with significantly lower thickness, area, and volume and higher mean curvature than HCs. Potential atrophy predominately presented in the frontal lobe (cumulative weight = 4.3725, contribution rate of 29.86%), and temporal lobe (cumulative weight = 2.573, contribution rate of 17.57%). The NMDARE versus VE model achieved certain diagnostic power, with AUC of 0.879 in validation set. Our research shows potential atrophy across the entire cerebral cortex in acute NMDARE patients, and MRI machine learning model has a potential to facilitate the diagnosis MRI-negative NMDARE.

HOIP modulates the stability of GPx4 by linear ubiquitination.

LUBAC-mediated linear ubiquitination plays a pivotal role in regulation of cell death and inflammatory pathways. Genetic deficiency in LUBAC components leads to severe immune dysfunction or embryonic lethality. LUBAC has been extensively studied for its role in mediating TNF signaling. However, Tnfr1 knockout is not able to fully rescue the embryonic lethality of LUBAC deficiency, suggesting that LUBAC may modify additional key cellular substrates in promoting cell survival. GPx4 is an important selenoprotein involved in regulating cellular redox homeostasis in defense against lipid peroxidation-mediated cell death known as ferroptosis. Here we demonstrate that LUBAC deficiency sensitizes to ferroptosis by promoting GPx4 degradation and downstream lipid peroxidation. LUBAC binds and stabilizes GPx4 by modulating its linear ubiquitination both in normal condition and under oxidative stress. Our findings identify GPx4 as a key substrate of LUBAC and a previously unrecognized role of LUBAC-mediated linear ubiquitination in regulating cellular redox status and cell death.

SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination.

Stimulation of cells with TNFα leads to the formation of the TNF-R1 signaling complex (TNF-RSC) to mediate downstream cellular fate decision. Activation of the TNF-RSC is modulated by different types of ubiquitination and may lead to cell death, including apoptosis and necroptosis, in both RIPK1-dependent and RIPK1-independent manners. Spata2 (spermatogenesis-associated 2) is an adaptor protein recruited into the TNF-RSC to modulate the interaction between the linear ubiquitin chain assembly complex (LUBAC) and the deubiquitinase CYLD (cylindromatosis). However, the mechanism by which Spata2 regulates the activation of RIPK1 is unclear. Here, we report that Spata2-deficient cells show resistance to RIPK1-dependent apoptosis and necroptosis and are also partially protected against RIPK1-independent apoptosis. Spata2 deficiency promotes M1 ubiquitination of RIPK1 to inhibit RIPK1 kinase activity. Furthermore, we provide biochemical evidence for the USP domain of CYLD and the PUB domain of the SPATA2 complex preferentially deubiquitinating the M1 ubiquitin chain in vitro. Spata2 deficiency also promotes the activation of MKK4 and JNK and cytokine production independently of RIPK1 kinase activity. Spata2 deficiency sensitizes mice to systemic inflammatory response syndrome (SIRS) induced by TNFα, which can be suppressed by RIPK1 inhibitor Nec-1s. Thus, Spata2 can regulate inflammatory response and cell death in both RIPK1-dependent and RIPK1-independent manners.

Probing Homogeneous Catalysts and Precatalysts in Solution by Exchange-Mediated Overhauser Dynamic Nuclear Polarization NMR.

Triphenylphosphine (PPh3) is a ubiquitous ligand in organometallic chemistry that has been shown to give enhanced 31P NMR signals at high magnetic field via a scalar-dominated Overhauser effect dynamic nuclear polarization (OE DNP). However, PPh3 can only be polarized via DNP in the free form, while the coordinated form is DNP-inactive. Here, we demonstrate the possibility of enhancing the 31P NMR signals of coordinated PPh3 in metal complexes in solution at room temperature by combining Overhauser effect DNP and chemical exchange between the free and coordinated PPh3 forms. With this method, we successfully obtain 31P DNP enhancements of up to 2 orders of magnitude for the PPh3 ligands in Rh(I), Ru(II), Pd(II), and Pt(II) complexes, and we show that the DNP enhancements can be used to determine the activation energy of the ligand exchange reaction.

Enlarged tumour-draining lymph node with immune-activated profile predict favourable survival in non-metastatic colorectal cancer.

BACKGROUND: The tumour-draining lymph node (TDLN) plays a pivotal role in the suppression of malignant tumour, however, the immunological profile and prognostic differences between large TDLN (L-TDLN) and small TDLN (S-TDLN) in colorectal cancer (CRC) remain unclear. METHODS: We conducted a study using data from the Chinese National Cancer Center (CNCC) database, identifying 837 CRC patients with non-metastatic TDLN, and categorised them into L-TDLN and S-TDLN groups. The long-term survival outcomes and adjuvant therapy efficacy were compared between the two groups. Furthermore, we evaluated the differences in immune activation status and immune cell subsets between patients in L-TDLN and S-TDLN groups by RNA sequencing and immunohistochemical (IHC) staining. RESULTS: Patients with L-TDLN demonstrated better long-term outcomes compared to those with S-TDLN. Among patients with L-TDLN, there was no significant difference in long-term outcomes between those who received adjuvant chemotherapy and those who did not. The RNA sequencing data revealed a wealth of immune-activating pathways explored in L-TDLN. Furthermore, IHC analysis demonstrated higher numbers of CD3+ and CD8 + T cells in L-TDLN and the corresponding CRC lesions, as compared to patients with S-TDLN. CONCLUSION: Enlarged TDLN exhibited an activated anti-tumour immune profile and may serve as an indicator for favourable survival in non-metastatic CRC.

Machine learning-based decision support model for selecting intra-arterial therapies for unresectable hepatocellular carcinoma: A national real-world evidence-based study.

IMPORTANCE: Intra-arterial therapies(IATs) are promising options for unresectable hepatocellular carcinoma(HCC). Stratifying the prognostic risk before administering IAT is important for clinical decision-making and for designing future clinical trials. OBJECTIVE: To develop and validate a machine learning(ML)-based decision support model(MLDSM) for recommending IAT modalities for unresectable HCC. DESIGN, SETTING, AND PARTICIPANTS: Between October 2014 and October 2022, a total of 2,959 patients with HCC who underwent initial IATs were enroled retrospectively from 13 tertiary hospitals. These patients were divided into the training cohort (n = 1700), validation cohort (n = 428), and test cohort (n = 200). MAIN OUTCOMES AND MEASURES: Thirty-two clinical variables were input, and five supervised ML algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBM) and Random Forest (RF), were compared using the areas under the receiver operating characteristic curve (AUC) with the DeLong test. RESULTS: A total of 1856 patients were assigned to the IAT alone Group(I-A), and 1103 patients were assigned to the IAT combination Group(I-C). The 12-month death rates were 31.9% (352/1103) in the I-A group and 50.4% (936/1856) in the I-C group. For the test cohort, in the I-C group, the CatBoost model achieved the best discrimination when 30 variables were input, with an AUC of 0.776 (95% confidence intervals [CI], 0.833-0.868). In the I-A group, the LGBM model achieved the best discrimination when 24 variables were input, with an AUC of 0.776 (95% CI, 0.833-0.868). According to the decision trees, BCLC grade, local therapy, and diameter as top three variables were used to guide clinical decisions between IAT modalities. CONCLUSIONS AND RELEVANCE: The MLDSM can accurately stratify prognostic risk for HCC patients who received IATs, thus helping physicians to make decisions about IAT and providing guidance for surveillance strategies in clinical practice.

Systematic evaluation of the effect of polyadenylation signal variants on the expression of disease-associated genes.

Single nucleotide variants (SNVs) within polyadenylation signals (PASs), a specific six-nucleotide sequence required for mRNA maturation, can impair RNA-level gene expression and cause human diseases. However, there is a lack of genome-wide investigation and systematic confirmation tools for identifying PAS variants. Here, we present a computational strategy to integrate the most reliable resources for discovering distinct genomic features of PAS variants and also develop a credible and convenient experimental tool to validate the effect of PAS variants on expression of disease-associated genes. This approach will greatly accelerate the deciphering of PAS variation-related human diseases.

Cancer-associated dynamics and potential regulators of intronic polyadenylation revealed by IPAFinder using standard RNA-seq data.

Intronic polyadenylation (IpA) usually leads to changes in the coding region of an mRNA, and its implication in diseases has been recognized, although at its very beginning status. Conveniently and accurately identifying IpA is of great importance for further evaluating its biological significance. Here, we developed IPAFinder, a bioinformatic method for the de novo identification of intronic poly(A) sites and their dynamic changes from standard RNA-seq data. Applying IPAFinder to 256 pan-cancer tumor/normal pairs across six tumor types, we discovered 490 recurrent dynamically changed IpA events, some of which are novel and derived from cancer-associated genes such as TSC1, SPERD2, and CCND2 Furthermore, IPAFinder revealed that IpA could be regulated by factors related to splicing and m6A modification. In summary, IPAFinder enables the global discovery and characterization of biologically regulated IpA with standard RNA-seq data and should reveal the biological significance of IpA in various processes.

Effects of acetazolamide combined with remote ischemic preconditioning on risk of acute mountain sickness: a randomized clinical trial.

BACKGROUND: We aimed to determine whether and how the combination of acetazolamide and remote ischemic preconditioning (RIPC) reduced the incidence and severity of acute mountain sickness (AMS). METHODS: This is a prospective, randomized, open-label, blinded endpoint (PROBE) study involving 250 healthy volunteers. Participants were randomized (1:1:1:1:1) to following five groups: Ripc (RIPC twice daily, 6 days), Rapid-Ripc (RIPC four times daily, 3 days), Acetazolamide (twice daily, 2 days), Combined (Acetazolamide plus Rapid-Ripc), and Control group. After interventions, participants entered a normobaric hypoxic chamber (equivalent to 4000 m) and stayed for 6 h. The primary outcomes included the incidence and severity of AMS, and SpO2 after hypoxic exposure. Secondary outcomes included systolic and diastolic blood pressure, and heart rate after hypoxic exposure. The mechanisms of the combined regime were investigated through exploratory outcomes, including analysis of venous blood gas, complete blood count, human cytokine antibody array, ELISA validation for PDGF-AB, and detection of PDGF gene polymorphisms. RESULTS: The combination of acetazolamide and RIPC exhibited powerful efficacy in preventing AMS, reducing the incidence of AMS from 26.0 to 6.0% (Combined vs Control: RR 0.23, 95% CI 0.07-0.70, P = 0.006), without significantly increasing the incidence of adverse reactions. Combined group also showed the lowest AMS score (0.92 ± 1.10). Mechanistically, acetazolamide induced a mild metabolic acidosis (pH 7.30 ~ 7.31; HCO3- 18.1 ~ 20.8 mmol/L) and improved SpO2 (89 ~ 91%) following hypoxic exposure. Additionally, thirty differentially expressed proteins (DEPs) related to immune-inflammatory process were identified after hypoxia, among which PDGF-AB was involved. Further validation of PDGF-AB in all individuals showed that both acetazolamide and RIPC downregulated PDGF-AB before hypoxic exposure, suggesting a possible protective mechanism. Furthermore, genetic analyses demonstrated that individuals carrying the PDGFA rs2070958 C allele, rs9690350 G allele, or rs1800814 G allele did not display a decrease in PDGF-AB levels after interventions, and were associated with a higher risk of AMS. CONCLUSIONS: The combination of acetazolamide and RIPC exerts a powerful anti-hypoxic effect and represents an innovative and promising strategy for rapid ascent to high altitudes. Acetazolamide improves oxygen saturation. RIPC further aids acetazolamide, which synergistically regulates PDGF-AB, potentially involved in the pathogenesis of AMS. TRIAL REGISTRATION: ClinicalTrials.gov NCT05023941.

Development of Injectable Thermosensitive Nanocomposite Hydrogel for Ratiometric Drug Delivery to Treat Drug Resistant Chondrosarcoma In Vivo.

Chondrosarcoma(CS), a prevalent primary malignant bone tumor, frequently exhibits chemotherapy resistance attributed to upregulated anti-apoptosis pathways such as the Bcl-2 family. In this manuscript, a new strategy is presented to augment chemosensitivity and mitigate systemic toxicity by harnessing a nano-enabled drug delivery hydrogel platform. The platform utilizes "PLGA-PEG-PLGA", an amphiphilic triblock copolymer combining hydrophilic polyethylene glycol (PEG) and hydrophobic polylactide glycolide (PLGA) blocks, renowned for its properties conducive to crafting a biodegradable, temperature-sensitive hydrogel. This platform is tailored to encapsulate a ratiometrically designed dual-loaded liposomes containing a first-line chemo option for CS, Doxorubicin (Dox), plus a calculated amount of small molecule inhibitor for anti-apoptotic Bcl-2 pathway, ABT-737. In vitro and in vivo evaluations demonstrate successful Bcl-2 suppression, resulting in the restoration of Dox sensitivity, evident through impeded tumor growth and amplified necrosis rates at the tumor site. This delivery system showcases remarkable thermal responsiveness, injectability, and biodegradability, all finely aligned with the clinical demands of CS treatment. Collectively, this study introduces a transformative avenue for tackling drug resistance in CS chemotherapy, offering significant clinical potential.

Simulation of gradient period polarization volume gratings for augmented reality displays.

Augmented reality (AR) displays are gaining attention as next-generation intelligent display technologies. Diffractive waveguide technologies are progressively becoming the AR display industry's preferred option. Gradient period polarization volume holographic gratings (PVGs), which are considered to have the potential to expand the field of view (FOV) of waveguide display systems due to their wide bandwidth diffraction characteristics, have been proposed as coupling elements for diffraction waveguide systems in recent years. Here, what we believe to be a novel modeling method for gradient period PVGs is proposed by incorporating grating stacking and scattering analysis utilizing rigorous coupled-wave analysis (RCWA) theory. The diffraction efficiency and polarization response were extensively explored using this simulation model. In addition, a dual-layer full-color diffractive waveguide imaging simulation using proposed gradient period PVGs is accomplished in Zemax software using a self-compiled dynamic link library (DLL), achieving a 53° diagonal FOV at a 16:9 aspect ratio. This work furthers the development of PVGs by providing unique ideas for the field of view design of AR display.

Simultaneous Rosiglitazone Release and Low-Density Lipoprotein Removal by Chondroitin Sodium Sulfate/Cyclodextrin/Poly(acrylic acid) Composite Adsorbents for Atherosclerosis Therapy.

Atherosclerosis (AS) is characterized by the accumulation of substantial low-density lipoprotein (LDL) and inflammatory response. Hemoperfusion is commonly employed for the selective removal of LDL from the body. However, conventional hemoperfusion merely focuses on LDL removal and does not address the symptom of plaque associated with AS. Based on the LDL binding properties of acrylated chondroitin sodium sulfate (CSA), acrylated beta-cyclodextrin (CD) and acrylic acid (AA), along with the anti-inflammatory property of rosiglitazone (R), the fabricated AA-CSA-CD-R microspheres could simultaneously release R and facilitate LDL removal for hemoperfusion. The AA and CSA offer electrostatic adsorption sites for LDL, while the CD provides hydrophobic adsorption sites for LDL and weak binding sites for R. According to the Sips model, the maximum static LDL adsorption capacity of AA-CSA-CD-R is determined to be 614.73 mg/g. In dynamic simulated perfusion experiments, AA-CSA-CD-R exhibits an initial cycle LDL adsorption capacity of 150.97 mg/g. The study suggests that the weakened inflammatory response favors plaque stabilization. The anti-inflammatory property of the microspheres is verified through an inflammation model, wherein the microsphere extracts are cocultured with mouse macrophages. Both qualitative analysis of iNOS\TNF-α and quantitative analysis of IL-6\TNF-α collectively demonstrate the remarkable anti-inflammatory effect of the microspheres. Therefore, the current study presents a novel blood purification treatment of eliminating pathogenic factors and introducing therapeutic factors to stabilize AS plaque.

'Out of Africa' origin of the pantropical staghorn fern genus Platycerium (Polypodiaceae) supported by plastid phylogenomics and biogeographical analysis.

BACKGROUND AND AIMS: The staghorn fern genus Platycerium is one of the most commonly grown ornamental ferns, and it evolved to occupy a typical pantropical intercontinental disjunction. However, species-level relationships in the genus have not been well resolved, and the spatiotemporal evolutionary history of the genus also needs to be explored. METHODS: Plastomes of all the 18 Platycerium species were newly sequenced. Using plastome data, we reconstructed the phylogenetic relationships among Polypodiaceae members with a focus on Platycerium species, and further conducted molecular dating and biogeographical analyses of the genus. KEY RESULTS: The present analyses yielded a robustly supported phylogenetic hypothesis of Platycerium. Molecular dating results showed that Platycerium split from its sister genus Hovenkampia ~35.2 million years ago (Ma) near the Eocene-Oligocene boundary and began to diverge ~26.3 Ma during the late Oligocene, while multiple speciation events within Platycerium occurred during the middle to late Miocene. Biogeographical analysis suggested that Platycerium originated in tropical Africa and then dispersed eastward to southeast Asia-Australasia and westward to neotropical areas. CONCLUSIONS: Our analyses using a plastid phylogenomic approach improved our understanding of the species-level relationships within Platycerium. The global climate changes of both the Late Oligocene Warming and the cooling following the mid-Miocene Climate Optimum may have promoted the speciation of Platycerium, and transoceanic long-distance dispersal is the most plausible explanation for the pantropical distribution of the genus today. Our study investigating the biogeographical history of Platycerium provides a case study not only for the formation of the pantropical intercontinental disjunction of this fern genus but also the 'out of Africa' origin of plant lineages.

Prognosis prediction and risk stratification of transarterial chemoembolization or intraarterial chemotherapy for unresectable hepatocellular carcinoma based on machine learning.

OBJECTIVE: To develop and validate a risk scoring scale model (RSSM) for stratifying prognostic risk after intra-arterial therapies (IATs) for hepatocellular carcinoma (HCC). METHODS: Between February 2014 and October 2022, 2338 patients with HCC who underwent initial IATs were consecutively enrolled. These patients were divided into training datasets (TD, n = 1700), internal validation datasets (ITD, n = 428), and external validation datasets (ETD, n = 200). Five-years death was used to predict outcome. Thirty-four clinical information were input and five supervised machine learning (ML) algorithms, including eXtreme Gradient Boosting (XGBoost), Categorical Gradient Boosting (CatBoost), Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LGBT), and Random Forest (RF), were compared using the areas under the receiver operating characteristic (AUC) with DeLong test. The variables with top important ML scores were used to build the RSSM by stepwise Cox regression. RESULTS: The CatBoost model achieved the best discrimination when 12 top variables were input, with the AUC of 0.851 (95% confidence intervals (CI), 0.833-0.868) for TD, 0.817 (95%CI, 0.759-0.857) for ITD, and 0.791 (95%CI, 0.748-0.834) for ETD. The RSSM was developed based on the immune checkpoint inhibitors (ICI) (hazard ratios (HR), 0.678; 95%CI 0.549, 0.837), tyrosine kinase inhibitors (TKI) (HR, 0.702; 95%CI 0.605, 0.814), local therapy (HR, 0.104; 95%CI 0.014, 0.747), response to the first IAT (HR, 4.221; 95%CI 2.229, 7.994), tumor size (HR, 1.054; 95%CI 1.038, 1.070), and BCLC grade (HR, 2.375; 95%CI 1.950, 2.894). Kaplan-Meier analysis confirmed the role of RSSM in risk stratification (p < 0.001). CONCLUSIONS: The RSSM can stratify accurately prognostic risk for HCC patients received IAT. On the basis, an online calculator permits easy implementation of this model. CLINICAL RELEVANCE STATEMENT: The risk scoring scale model could be easily implemented for physicians to stratify risk and predict prognosis quickly and accurately, thereby serving as a more favorable tool to strengthen individualized intra-arterial therapies and management in patients with unresectable hepatocellular carcinoma. KEY POINTS: • The Categorical Gradient Boosting (CatBoost) algorithm achieved the optimal and robust predictive ability (AUC, 0.851 (95%CI, 0.833-0.868) in training datasets, 0.817 (95%CI, 0.759-0.857) in internal validation datasets, and 0.791 (95%CI, 0.748-0.834) in external validation datasets) for prediction of 5-years death of hepatocellular carcinoma (HCC) after intra-arterial therapies (IATs) among five machine learning models. • We used the SHapley Additive exPlanations algorithms to explain the CatBoost model so as to resolve the black boxes of machine learning principles. • A simpler restricted variable, risk scoring scale model (RSSM), derived by stepwise Cox regression for risk stratification after intra-arterial therapies for hepatocellular carcinoma, provides the potential forewarning to adopt combination strategies for high-risk patients.

Parental communicative input as a protective factor in Bangladeshi families living in poverty: A multi-dimensional perspective.

Studies from high-income populations have shown that stimulating, supportive communicative input from parents promote children's cognitive and language development. However, fewer studies have identified specific features of input supporting the healthy development of children growing up in low- or middle-income countries. The current study proposes and tests a multi-dimensional framework for understanding whether and how caregiver communicative input mediates the associations between socio-economic conditions and early development. We also examine how caregiver conceptual scaffolding and autonomy support uniquely and synergistically explain variation in child outcomes. Participants were 71 Bangladeshi families with five-year-olds who were exposed to a range of biological and psychosocial hazards from birth. Caregiver-child interactions during snack sharing and semi-structured play were coded for caregiver conceptual scaffolding, autonomy support, and child engagement. Findings indicate that the two dimensions of input were correlated, suggesting that caregivers who provided richer conceptual scaffolds were simultaneously more supportive of children's autonomy. Notably, conceptual scaffolding and autonomy support each mediated associations between maternal education and child verbal intelligence quotient (IQ) scores. Further, caregivers who supported greater autonomy in their children had children who participated in conversations more actively, and these children in turn had higher performance IQ scores. When considered simultaneously, conceptual scaffolding was associated with verbal IQ over and above autonomy support, whereas autonomy support related to child engagement, controlling for conceptual scaffolding. These findings shed new light on how environmental factors may support early development, contributing to the design of family-centered, culturally authentic interventions. A video abstract of this article can be viewed at https://youtu.be/9v_8sIv7ako RESEARCH HIGHLIGHTS: Studies from high-income countries have identified factors mitigating the impacts of socio-economic risks on development. Such research is scarce in low- and middle-income countries. The present study conceptualized and evaluated caregiver communicative input in Bangladeshi families along two interrelated yet distinct dimensions: conceptual scaffolding and autonomy support. Conceptual scaffolding and autonomy support individually mediated associations between maternal education and child verbal IQ, shedding light on protective factors in families living in poverty. Parents providing richer conceptual scaffolds were simultaneously more supportive of children's autonomy. However, the two dimensions each related to cognition and language through unique pathways.

The influence of heteroatoms on the circularly polarized luminescence performance of [7]helicene derivatives: aromatic vs. non-aromatic five-membered rings.

Helicenes are promising candidates for circularly polarized luminescence (CPL) materials, although the performance is poor due to the unsatisfactory dissymmetric factor (glum) and fluorescence quantum efficiency (ΦF). Herein, the influence of heteroatoms (C, Si, Ge, O, S and Se) on the electronic structures and chiroptical properties of [7]helicene derivatives is systematically investigated using density functional theory (DFT) and time-dependent DFT calculations combined with the thermal vibration correlation function theory. The results reveal that the non-radiative energy consumption processes for helicene systems are closely related to the variation of bond length upon electronic excitation. Moreover, by introducing five-membered rings and heteroatoms, the dipole-forbidden S1 → S0 emission of [7]helicene changes to dipole-allowed transition due to the rearrangement of occupied orbitals and lifting of the nearly degenerate orbitals, resulting in an enhancement of ΦF. As the heteroatomic radius increases, ΦF decreases while the glum increases. Compared with the derivatives containing aromatic five-membered rings ([7]H-O, [7]H-S, and [7]H-Se), the non-aromatic counterparts ([7]H-C, [7]H-Si, and [7]H-Ge) exhibit a balance in ΦF and glum values. The present study helps to clarify the relationship between structures and chiroptical properties and offers a feasible strategy for the future design of helicene-based CPL materials.

Associations between bone mineral density and abdominal aortic calcification: Results of a nationwide survey.

BACKGROUND AND AIMS: Vascular calcification has been linked to bone mineral density (BMD). This study aimed to investigate the association between BMD and abdominal aortic calcification (AAC). METHODS AND RESULTS: Data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were utilized. Participants lacking BMD and AAC score data were excluded. BMD at the femoral neck was measured using dual-energy X-ray absorptiometry. AAC scores were assessed using the Kauppila scoring system, with AAC defined as a score greater than zero, and severe AAC defined as a score greater than six. Weighted multivariable regression analysis and subgroup analysis were conducted to examine the independent relationship between BMD and AAC score, AAC, and severe AAC. A total of 2965 participants were included. After adjusting for multiple covariates, BMD showed a negative association with higher AAC scores (ß = -0.17, 95% CI -0.29, -0.05, p = 0.0066). The odds of having AAC and severe AAC decreased by 9% and 16%, respectively, for every one-unit increase in BMD (AAC: odds ratio [OR] = 0.91, 95% CI 0.82, 1.00, p = 0.0431; severe AAC: OR = 0.84, 95% CI 0.71, 0.99, p = 0.0334). CONCLUSION: Low BMD is associated with higher AAC scores and an increased risk of AAC and severe AAC. Considering the detrimental impact of low BMD on cardiovascular health, individuals with AAC should be evaluated for osteopenia and osteoporosis in clinical settings.

Tumor-derived KLK8 predicts inferior survival and promotes an immune-suppressive tumor microenvironment in lung squamous cell carcinoma.

Lung squamous cell carcinoma (LUSC) is the second most common lung cancer worldwide, leading to millions of deaths annually. Although immunotherapy has expanded the therapeutic choices for LUSC and achieved considerable efficacy in a subset of patients, many patients could not benefit, and resistance was pervasive. Therefore, it is significant to investigate the mechanisms leading to patients' poor response to immunotherapies and explore novel therapeutic targets. Using multiple public LUSC datasets, we found that Kallikrein-8 (KLK8) expression was higher in tumor samples and was correlated with inferior survival. Using a LUSC cohort (n = 190) from our center, we validated the bioinformatic findings about KLK8 and identified high KLK8 expression as an independent risk factor for LUSC. Function enrichment showed that several immune signaling pathways were upregulated in the KLK8 low-expression group and downregulated in the KLK8 high-expression group. For patients with low KLK8 expression, they were with a more active TME, which was both observed in the TCGA database and immune marker immunohistochemistry, and they had extensive positive relations with immune cells with tumor-eliminating functions. This study identified KLK8 as a risk factor in LUSC and illustrated the associations between KLK8 and cancer immunity, suggesting the potentiality of KLK8 as a novel immune target in LUSC.

Two-step osteotomy/discectomy through cannulated screw (TOCS) technique for en bloc resection of spine tumor: surgical technique and preliminary results.

PURPOSE: We have developed a novel technique for osteotomy/discectomy during en bloc resection of spine tumors named two-step osteotomy/discectomy through cannulated screw (TOCS). This study aims at describing the procedure of TOCS technique and assessing its efficiency and safety. METHODS: We retrospectively reviewed fourteen patients who underwent en bloc resection for spine tumors using TOCS technique in our center between August 2018 and September 2022. The technique was based on a specially designed "slotted" cannulated screw which was a cannulated screw with a longitudinal slot to provide the accessibility of T-saw. During osteotomy/discectomy, the "slotted" cannulated screw was inserted obliquely along the plane between the dura and the posterior wall of spine in light of the planned osteotomy/discectomy plane under routine fluoroscopic imaging guidance. The T-saw was introduced through the screw, and the osteotomy/discectomy was performed sequentially in two steps under the guidance of the screw by turning the slot away and toward the dura. The intra-/perioperative complication, neurological function (determined by Frankel grading), surgical margin (determined by a pathologist using AJCC R system), follow-up details were documented. RESULTS: The mean duration of surgery was 599.3 (360-890) min with a mean volume of intra-operative hemorrhage of 2021.4 (800-5000) mL. The intra-/perioperative complications were found in four patients (28.6%). R0 and R1 resections were achieved in nine and five patients, respectively. There was no R2 resection. After a mean follow-up period of 30.6 (10-67) months, all patients were alive except one patient died ten months after surgery due to unrelated cause. No recurrence and implant failure were found. Thirteen patients (92.9%) exhibited completely normal neurological function same as their preoperative neurological status. CONCLUSION: Using TOCS technique can facilitate a precise, complete and safe osteotomy/discectomy procedure during en bloc resection for spine tumor without the aid of intra-operative navigation.

Prognostic and predictive value of examined lymph node count in stage III colorectal cancer: a population based study.

BACKGROUND: The role of tumor-draining lymph nodes in the progression of malignant tumors, including stage III colorectal cancer (CRC), is critical. However, the prognostic and predictive value of the number of examined lymph nodes (ELNs) are not fully understood. METHODS: This population-based study retrospectively analyzed data from 106,843 patients with stage III CRC who underwent surgical treatment and registered in three databases from 2004 to 2021. The Surveillance, Epidemiology, and End Results (SEER) cohort was divided using into training and test cohorts at a ratio of 3:2. We employed restricted cubic spline (RCS) curves to explore nonlinear relationships between overall survival (OS) and ELNs counts and performed Cox regression to evaluate hazard ratios across different ELNs count subtypes. Additional validation cohorts were utilized from the First Affiliated Hospital, Sun Yat-sen University and The Cancer Genome Atlas (TCGA) under the same criteria. Outcomes measured included OS, cancer-specific survival (CSS), and progression-free survival (PFS). Molecular analyses involved differential gene expression using the "limma" package and immune profiling through CIBERSORT. Tissue microarray slides and multiplex immunofluorescence (MIF) were used to assess protein expression and immune cell infiltration. RESULTS: Patients with higher ELNs counts (≥ 17) demonstrated significantly better long-term survival outcomes across all cohorts. Enhanced OS, CSS, and PFS were notably evident in the LN-ELN group compared to those with fewer ELNs. Cox regression models underscored the prognostic value of higher ELNs counts across different patient subgroups by age, sex, tumor differentiation, and TNM stages. Subtype analysis based on ELNs count revealed a marked survival benefit in patients treated with adjuvant chemotherapy in the medium and large ELNs counts (≥ 12), whereas those with fewer ELNs showed negligible benefits. RNA sequencing and MIF indicated elevated immune activation in the LN-ELN group, characterized by increased CD3+, CD4+, and CD8 + T cells within the tumor microenvironment. CONCLUSIONS: The number of ELNs independently predicts survival and the immunological landscape at the tumor site in stage III CRC, underscoring its dual prognostic and predictive value.