Clinical implications of hemodynamic analysis for the three-dimension iliac vein model with different stenosis.

Background: The aim of this study was to perform hemodynamic simulations of a three-dimension ideal inferior vena cava-iliac vein model with artificial stenosis to determine the degree of stenosis that requires clinical intervention. Methods: Four three-dimension stenosis models (30%, 50%, 70%, and 90% stenosis) were constructed using commercial software (Solidworks). The inlet flow rates were acquired from previous literatures to perform the hemodynamic simulations. Changes in the old blood volume fraction, as well conventional hemodynamic parameters including pressure, differential pressure, wall shear stress, and flow patterns, over time were recorded. The pressure at the telecentric region of the stenosis increased with increasing degree of stenosis. Results: For the 70% stenosis model, the pressure at the telecentric region of the stenosis reached 341 Pa, and the differential pressure between the two ends of the stenosis was 363 Pa (approximately 2.7 mmHg). Moreover, in the 70% and 90% stenosis models, there was a marked change in wall shear stress in the stenosis and the proximal end region, and the flow patterns began to show the phenomenon of flow separation. Blood stasis analysis showed that the 70% stenosis model had the slowest decrease in old blood volume fraction, while the proximal end region had the largest blood residue (15%). Conclusion: Iliac vein stenosis of approximately 70% is associated with clinically relevant hemodynamic changes, and is more closely related to DVT than other degrees of stenosis.

[Knockdown of lncRNA CACNA1C-AS2 promotes epithelial-mesenchymal transition and enhances the proliferation, invasion and migration of human esophageal cancer cells].

Objective To investigate the effect of calcium voltage gated channel subunit α 1C antisense RNA2 (CACNA1C-AS2) on malignant biological characteristics of esophageal cancer cells by regulating epithelial mesenchymal transition (EMT). Methods CACNA1C-AS2 expression levels in paracancerous tissues and esophageal cancer tissues were analyzed by TCGA database. Real-time quantitative PCR was used to detect the expression of CACNA1C-AS2 mRNA in esophageal cancer cells. Following the knockdown and high expression of CACNA1C-AS2 in esophageal cancer cells, the viability of the cells was tested by MTT assay and cell colony formation assay. TranswellTM chamber method was used to measure the invasion and longitudinal migration of the cells. The horizontal migration ability of the cells was evaluated by wound healing test. The apoptosis rates of cells were detected by flow cytometry. Western blot analysis was used to detect the expressions of N-cadherin, vimentin and slug. Results CACNA1C-AS2 expression levels were low in esophageal cancer tissues and cell lines. After knocking down the expression of CACNA1C-AS2 in EC-9706 cells and Eca-109 cells, the ability of invasion and migration and viability of esophageal cancer cells were significantly enhanced, and the apoptosis rates were decreased, while the expressions of N-cadherin, vimentin and slug were up-regulated. However, the results are opposite via the over-expression of CACNA1C-AS2. Conclusion CACNA1C-AS2 enhances the proliferation, invasion and migration of esophageal cancer cells by promoting EMT.

TLR2-hif1α-mediated glycolysis contributes to pyroptosis and oxidative stress in allergic airway inflammation.

As a pattern recognition receptor which activates innate immune system, toll-like receptor 2 (TLR2) has been reportedly mediates allergic airway inflammation (AAI), yet the underlying mechanism remains elusive. Here, in a murine AAI model, TLR2-/- mice showed decreased airway inflammation, pyroptosis and oxidative stress. RNA-sequencing revealed that allergen-induced hif1 signaling pathway and glycolysis were significantly downregulated when TLR2 was deficient, which were confirmed by lung protein immunoblots. Glycolysis inhibitor 2-Deoxy-d-glucose (2-DG) inhibited allergen-induced airway inflammation, pyroptosis, oxidative stress and glycolysis in wild type (WT) mice, while hif1α stabilizer ethyl 3,4-dihydroxybenzoate (EDHB) restored theses allergen-induced changes in TLR2-/- mice, indicating TLR2-hif1α-mediated glycolysis contributes to pyroptosis and oxidative stress in AAI. Moreover, upon allergen challenge, lung macrophages were highly activated in WT mice but were less activated in TLR2-/- mice, 2-DG replicated while EDHB reversed such effect of TLR2 deficiency on lung macrophages. Likewise, both in vivo and ex vivo WT alveolar macrophages (AMs) exhibited higher TLR2/hif1α expression, glycolysis and polarization activation in response to ovalbumin (OVA), which were all inhibited in TLR2-/- AMs, suggesting AMs activation and metabolic switch are dependent on TLR2. Finally, depletion of resident AMs in TLR2-/- mice abolished while transfer of TLR2-/- resident AMs to WT mice replicated the protective effect of TLR2 deficiency on AAI when administered before allergen challenge. Collectively, we suggested that loss of TLR2-hif1α-mediated glycolysis in resident AMs ameliorates allergic airway inflammation that inhibits pyroptosis and oxidative stress, therefore the TLR2-hif1α-glycolysis axis in resident AMs may be a novel therapeutic target for AAI.

Identification of QTL for reducing loss of grain yield under salt stress conditions in bi-parental populations derived from wheat landrace Hongmangmai.

KEY MESSAGE: A novel QTL (QSt.nftec-2BL) was mapped to a 0.7 cM interval on chromosome 2B. Plants carrying QSt.nftec-2BL produced higher grain yields by up to 21.4% than otherwise in salinized fields. Wheat yield has been limited by soil salinity in many wheat-growing areas globally. The wheat landrace Hongmangmai (HMM) possesses salt tolerance as it produced higher grain yields than other tested wheat varieties including Early Premium (EP) under salt stresses. To detect QTL underlying this tolerance, wheat cross EP × HMM was chosen to serve as mapping population that was homozygous at Ppd (photoperiod response gene), Rht (reduced plant height gene) and Vrn (vernalization gene); thus, interference with QTL detection by these loci could be minimized. QTL mapping was conducted firstly using 102 recombinant inbred lines (RILs) that were selected from the EP × HMM population (827 RILs) for similarity in grain yield under non-saline condition. Under salt stresses, however, the 102 RILs varied significantly in grain yield. These RILs were genotyped using a 90 K SNP (single nucleotide polymorphism) array; consequently, a QTL (QSt.nftec-2BL) was detected on chromosome 2B. Then, using 827 RILs and new simple sequence repeat (SSR) markers developed according to the reference sequence IWGSC RefSeq v1.0, location of QSt.nftec-2BL was refined to a 0.7 cM (6.9 Mb) interval flanked by SSR markers 2B-557.23 and 2B-564.09. Selection for QSt.nftec-2BL was performed based on the flanking markers using two bi-parental wheat populations. Trials for validating effectiveness of the selection were conducted in salinized fields in two geographical areas and two crop seasons, demonstrating that wheat plants with the salt-tolerant allele in homozygous status at QSt.nftec-2BL produced higher grain yields by up to 21.4% than otherwise.

Genome-Wide Analysis of the LATERAL ORGAN BOUNDARIES Domain (LBD) Members in Alfalfa and the Involvement of MsLBD48 in Nitrogen Assimilation.

The LATERAL ORGAN BOUNDARIES DOMAIN (LBD) proteins, a transcription factor family specific to the land plants, have been implicated in multiple biological processes including organ development, pathogen response and the uptake of inorganic nitrogen. The study focused on LBDs in legume forage Alfalfa. The genome-wide analysis revealed that in Alfalfa 178 loci across 31 allelic chromosomes encoded 48 unique LBDs (MsLBDs), and the genome of its diploid progenitor M. sativa spp. Caerulea encoded 46 LBDs. Synteny analysis indicated that the expansion of AlfalfaLBDs was attributed to the whole genome duplication event. The MsLBDs were divided into two major phylogenetic classes, and the LOB domain of the Class I members was highly conserved relative to that of the Class II. The transcriptomic data demonstrated that 87.5% of MsLBDs were expressed in at least one of the six test tissues, and Class II members were preferentially expressed in nodules. Moreover, the expression of Class II LBDs in roots was upregulated by the treatment of inorganic nitrogen such as KNO3 and NH4Cl (0.3 mM). The overexpression of MsLBD48, a Class II member, in Arabidopsis resulted in growth retardance with significantly declined biomass compared with the non-transgenic plants, and the transcription level of the genes involved in nitrogen uptake or assimilation, including NRT1.1, NRT2.1, NIA1 and NIA2 was repressed. Therefore, the LBDs in Alfalfa are highly conserved with their orthologs in embryophytes. Our observations that ectopic expression of MsLBD48 inhibited Arabidopsis growth by repressing nitrogen adaption suggest the negative role of the transcription factor in plant uptake of inorganic nitrogen. The findings imply the potential application of MsLBD48 in Alfalfa yield improvement via gene editing.

Exploring the Moderating Role of Ethnic Identity in the Relation Between Peer Stress and Life Satisfaction among Adolescents.

Objective: Ethnic identity is a crucial aspect of identity development during adolescence. This study aimed to examine the potential protective effect of ethnic identity in the relation between peer stress and global life satisfaction among adolescents. Method: Data were collected via self-report measures from 417 adolescents (ages 14 to 18, 63.0% girls; 32.6% African American, 32.1% European American, 15.0% Asian American, 10.5% Hispanic or Latinx, 6.6% Biracial or Multiracial, and 0.7% Other) at one public, urban high school. Results: The first model tested ethnic identity as the single moderator in the entire sample, and the moderation effect was not significant. The second model added ethnicity (African American vs. European American) as another moderator, and moderation effects were significant for both moderators. Furthermore, the negative effect of peer stress on life satisfaction was stronger for African American adolescents than European American counterparts. For both racial groups, the negative effect of peer stress on life satisfaction decreased as ethnic identity increased. The third model tested a three-way interaction across peer stress, ethnicity (African American vs. European American), and ethnic identity, which was not significant. Conclusions: The results supported the buffering effect of ethnic identity in the context of peer stress for both African American and European American adolescents, and such effect appears to be more important for protecting African American adolescents' life satisfaction, though these two moderators appear to work independently, rather than interact with each other and the peer stressor. Implications and future directions are discussed.

Itaconate Suppresses the Activation of Mitochondrial NLRP3 Inflammasome and Oxidative Stress in Allergic Airway Inflammation.

Itaconate has emerged as a novel anti-inflammatory and antioxidative endogenous metabolite, yet its role in allergic airway inflammation (AAI) and the underlying mechanism remains elusive. Here, the itaconate level in the lung was assessed by High Performance Liquid Chromatography (HPLC), and the effects of the Irg1/itaconate pathway on AAI and alveolar macrophage (AM) immune responses were evaluated using an ovalbumin (OVA)-induced AAI model established by wild type (WT) and Irg1-/- mice, while the mechanism of this process was investigated by metabolomics analysis, mitochondrial/cytosolic protein fractionation and transmission electron microscopy in the lung tissues. The results demonstrated that the Irg1 mRNA/protein expression and itaconate production in the lung were significantly induced by OVA. Itaconate ameliorated while Irg1 deficiency augmented AAI, and this may be attributed to the fact that itaconate suppressed mitochondrial events such as NLRP3 inflammasome activation, oxidative stress and metabolic dysfunction. Furthermore, we identified that the Irg1/itaconate pathway impacted the NLRP3 inflammasome activation and oxidative stress in AMs. Collectively, our findings provide evidence for the first time, supporting the conclusion that in the allergic lung, the itaconate level is markedly increased, which directly regulates AMs' immune responses. We therefore propose that the Irg1/itaconate pathway in AMs is a potential anti-inflammatory and anti-oxidative therapeutic target for AAI.

68Ga-FAPI PET/CT for Rheumatoid Arthritis: A Prospective Study.

Background In rheumatoid arthritis (RA), fibroblast-like synoviocyte cells, which are involved in inflammation of the articular cartilage and bone, overexpress fibroblast activation protein (FAP). This is a feature that could be leveraged to improve imaging assessment of disease. Purpose To determine the performance of gallium 68 (68Ga)-labeled FAP inhibitor (FAPI) in assessing joint disease activity of RA and to compare with fluorine 18 (18F) fluorodeoxyglucose (FDG) imaging. Materials and Methods Twenty participants with RA (15 women; mean age, 55 years ± 10 [SD]) were prospectively enrolled from September 2020 to December 2021 and underwent clinical and laboratory assessment of disease activity and dual-tracer PET/CT (68Ga-FAPI and 18F-FDG) imaging. Imaging-derived variables of PET joint count (the number of joints positive for RA at PET) and PET articular index (a sum of the points of the joints using a three-point scale) were correlated to clinical and laboratory variables of disease activity. Results The combined output of both PET/CT techniques helped detect 244 affected joints, all of which showed positive results at 68Ga-FAPI PET/CT. However, fifteen of 244 (6.1%) FAPI-avid joints in six of 20 (30%) participants were not detected at 18F-FDG PET/CT. The maximum standardized uptake value of the most affected joint in each participant was higher in 68Ga-FAPI than in 18F-FDG PET/CT (9.54 ± 4.92 vs 5.85 ± 2.81, respectively; P = .001). The maximum standardized uptake values of the joints at both 68Ga-FAPI and 18F-FDG PET/CT were positively correlated with laboratory evaluation of C-reactive protein levels (r = 0.49 [P = .03] and 0.54 [P = .01], respectively). The PET joint count and PET articular index scores at 68Ga-FAPI PET/CT were also positively correlated with most clinical disease activity variables and radiographic progression of joint damage (P < .05). Conclusion In participants with rheumatoid arthritis who underwent gallium 68 fibroblast activation protein inhibitor PET/CT, the extent of joint involvement correlated with clinical and laboratory variables of disease activity and showed a greater amount and degree of affected joints than at fluorine 18 fluorodeoxyglucose PET/CT. Clinical trial registration no. NCT04514614 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Williams and Ahlman in this issue.

A Non-Hydrolysis Reaction-Based Imine for Fluorescence Response toward Al3+ Ions with Extremely High Selectivity.

Designing an imine-based fluorescent probe capable of greatly suppressing the tendency of intrinsic hydrolysis reaction is an attractive topic in the field of chemo-/biosensing. In this work, hydrophobic 1,1'-binaphthyl-2,2'-diamine containing two amine groups was introduced to synthesize probe R-1 bearing two imine bonds linked by two salicylaldehyde (SAs). The hydrophobicity of binaphthyl moiety and the unique clamp-like structure formed from double imine bonds and from ortho-OH on SA part make probe R-1 is able to function as an ideal receptor to coordinate with Al3+ ions, leading to the fluorescence originated from the complex rather than from the assumed hydrolyzed fluorescent amine is turned on. Further study revealed that, when Al3+ ions were introduced, both the hydrophobic binaphthyl moiety and the clamp-like double imine structure in the designed imine-based probe showed important contributions to suppress the intrinsic hydrolysis reaction, resulting in generating a stable coordination complex with an extremely high selectivity in fluorescence response.

UPLC-MS based serum metabolomics for early diagnosis of refractory tumor-induced osteomalacia: a case-control study.

CONTEXT: Nearly 20% patients with Tumor-induced osteomalacia (TIO) experienced recurrence or nonrecovery after surgery. Serum FGF23 and phosphate concentrations are not capable for prognosis in such cases. Despite its importance for understanding of prognosis and underlying pathogenesis, the alteration of systemic metabolism in refractory TIO remains unclear. OBJECTIVE: We aimed to find the metabolomic characteristics of refractory TIO, and establish a novel predictive model for early discriminating refractory TIO based on their serum metabolomics. DESIGN AND SETTING: Cross-section study for comparison of metabolomic profile between TIO and normal control, and longitudinal study for identifying prognostic model. METHODS: Based on liquid chromatography-tandem mass spectrometry, we analyzed the global metabolomes of preoperative sera from 86 samples (32 TIO recovery patients, 11 non-remission patients and 43 matched controls). Statistical analyses, pathway enrichment and receiver operating characteristic analysis were performed to identified and evaluate potential markers. RESULTS: Sparse partial least squares discriminant analysis indicated a clear separation of metabolomic profiles between Healthy controls and TIO patients. The serum metabolites altered in different prognostic groups. L-Pipecolic acid, 2-Dodecylbenzenesulfonic acid and 2-Deoxygalactopyranose were the top 3 metabolites that were significantly perturbed. A combination of L-Pipecolic acid and 2-Dodecylbenzenesulfonic acid demonstrated a high-performance panel for TIO prognosis evaluated by random forest algorithm (AUC=0.921, 95% confidence interval of 0.787-0.995). CONCLUSIONS: We investigate the global metabolomes of refractory TIO and identify potential prognostic biomarkers preliminarily. A high sensitivity and specificity panel were identified as promising discriminating predictor, which need to be verified in more patients. This work may demonstrate novel insights into TIO prognosis and pathogenesis.

The super elongation complex (SEC) mediates phase transition of SPT5 during transcriptional pause release.

Release of promoter-proximally paused RNA Pol II into elongation is a tightly regulated and rate-limiting step in metazoan gene transcription. However, the biophysical mechanism underlying pause release remains unclear. Here, we demonstrate that the pausing and elongation regulator SPT5 undergoes phase transition during transcriptional pause release. SPT5 per se is prone to form clusters. The disordered domain in SPT5 is required for pause release and gene activation. During early elongation, the super elongation complex (SEC) induces SPT5 transition into elongation droplets. Depletion of SEC increases SPT5 pausing clusters. Furthermore, disease-associated SEC mutations impair phase properties of elongation droplets and transcription. Our study suggests that SEC-mediated SPT5 phase transition might be essential for pause release and early elongation and that aberrant phase properties could contribute to transcription abnormality in diseases.

Perinatal exposure to high concentration glyphosate-based herbicides induces intestinal apoptosis by activating endoplasmic reticulum stress in offspring.

Glyphosate-based herbicides (GBHs), the most widely used pesticide worldwide, have been reported to impair organ function in humans and animals. However, research on the effect of maternal GBHs exposure on the intestinal health of offspring has received little attention. Based on the glyphosate limits defined by Codex Alimentarius Commission and European Food Safety Authority, this study established pregnant sow exposure models to investigate the influence of low (L-GBHs, 20 mg/kg) and high concentration GBHs (H-GBHs, 100 mg/kg) on the intestinal health of offspring and proposed the protective mechanism mediated by betaine. The results showed that the intestinal morphology and barrier function of suckling piglets were damaged in the H-GBHs group. H-GBHs increased the activity of glutathione peroxidase (GPX) and levels of methane dicarboxylic aldehyde (MDA), hydrogen peroxide (H2O2) and inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10)) in suckling piglets and activated Nrf2-mediated antioxidant signaling pathway. Subsequently, we found that exposure to H-GBHs triggered endoplasmic reticulum stress (ERS) and further induced apoptosis by upregulating the expression of Bcl-2-associated X protein (Bax), Caspase3, Caspase9 and Caspase12. Moreover, H-GBHs exposure perturbed mitochondrial membrane fusion and electron transport in mitochondrial respiratory chains by increasing the mRNA expression of mitofusin-2 (MFN2) and succinate dehydrogenase subunit A (SDHA), causing mitochondrial dysfunction. Dietary supplementation with betaine provided modest protection against GBHs-induced intestinal damage in suckling piglets. These findings reveal the mechanism of GBHs-induced intestinal damage in offspring, improving our understanding of the risk of GBHs exposure in pregnant women and suggesting the potential protective effects of betaine against GBHs poisoning.

Morphology and Distribution of Antennal Sensilla in an Egg Parasitoid Wasp, Anastatus disparis (Hymenoptera: Eupelmidae).

The wasp Anastatus disparis is an egg endoparasitoid of a number of Lepidopteran pest species. To better understand the A. disparis olfactory system, we observed the antennal sensilla of males and females under a scanning electron microscope and quantified their sizes and morphological characteristics. We identified the types of sensilla and counted the numbers and locations of the different types on the dorsal and ventral antennal surfaces. The antennae of A. disparis are geniculate, with flagella that comprise 11 subsegments in females and eight in males. The mean antenna length was 1324.10 ± 52.50 µm in females and 1323.93 ± 65.20 µm in males. Ten sensillum types were identified in both sexes: Böhm bristles (BBs), sensilla trichodea (ST, with subtypes STI and STII), sensilla chaetica (SCh), sensilla basiconica (SB, with subtypes SBI and SBII), sensilla placodea (SP), sensilla coeleoconica (SCo), sensilla grooved peg (SGP), sensilla auricillica (SAu), sensilla campaniformia (SCa), and glandular pores (GPs). The total numbers of BBs, STI, SBII, SCa, SCo, and GPs did not differ significantly between the sexes, whereas the total numbers of SCh, SBI, and SAu were significantly greater in females, and those of STII, SP, and SGP were significantly lower. The types, number, and density of antennal sensilla increased from the base to the end. The possible functions of these sensilla in host-detection behavior are discussed.

Alterations of Regional Homogeneity in Parkinson's Disease with Rapid Eye Movement Sleep Behavior Disorder.

Objective: Patients with rapid eye movement (REM) sleep behavior disorder (RBD) in Parkinson's disease (PD-RBD) tend to have poor cognitive performance and faster cognitive deterioration, and the potential mechanism is still ambiguous. Therefore, this study aimed to detect the alterations in local brain function in PD-RBD. Methods: Fifty patients, including 23 patients with PD-RBD and 27 patients with PD without RBD (PD-nRBD), and 26 healthy controls were enrolled. All subjects were subjected to one-night polysomnography and underwent resting-state functional magnetic resonance imaging (rs-fMRI). The fMRI images of the three groups were analyzed by regional homogeneity (ReHo) to observe the local neural activity. Correlations between altered ReHo values and chin electromyographic (EMG) density scores and cognitive scores in the PD subgroups were assessed. Results: Compared with the patients with PD-nRBD, the patients with PD-RBD had higher ReHo values in the frontal cortex (the right superior frontal gyrus, the right middle frontal gyrus and the left medial superior frontal gyrus), the right caudate nucleus and the right anterior cingulate gyrus, and compared with the HCs, the patients with PD-RBD had lower ReHo values in the bilateral cuneus, the bilateral precuneus, the left inferior temporal gyrus and the left inferior occipital gyrus. For the patients with PD-RBD, the phasic chin EMG density scores were positively correlated with the ReHo values in the left medial superior frontal gyrus, and the tonic chin EMG density scores were positively correlated with the ReHo values in the right anterior cingulate gyrus. Conclusion: This study indicates that increased ReHo in the frontal cortex, the caudate nucleus and the anterior cingulate gyrus may be linked with the abnormal motor behaviors during REM sleep and that decreased ReHo in the posterior regions may be related to the visuospatial-executive function in patients with PD-RBD.

Achievements and Perspectives on Fe-Based Shape Memory Alloys for Rehabilitation of Reinforced Concrete Bridges: An Overview.

Reinforced concrete (RC) bridges often face great demands of strengthening or repair during their service life. Fe-based shape memory alloys (Fe-SMAs) as a kind of low-cost smart materials have great potential to enhance civil engineering structures. The stable shape memory effect of Fe-SMAs is generated by, taking Fe-Mn-Si alloys as an example, the martensite transformation of fcc(γ) → hcp(ε) and its reverse transformation which produces considerable recovery stress (400~500 MPa) that can be used as prestress for reinforcement of RC bridges. In this work, the mechanism, techniques, and applications of Fe-SMAs in the reinforcement of RC beams in the past two decades are classified and introduced in detail. Finally, some new perspectives on Fe-SMAs application in civil engineering and their expected evolution are proposed. This paper offers an effective active rehabilitation alternative for the traditional passive strengthening method of RC bridges.

Compound heterozygous loss-of-function variants in BRAT1 cause lethal neonatal rigidity and multifocal seizure syndrome.

BACKGROUND: Lethal neonatal rigidity and multifocal seizure syndrome (RMFSL, OMIM 614498) is a rare autosomal recessive disease characterized by the onset of rigidity and intractable seizures at or soon after birth. The BRAT1 has been identified to be the disease-causing gene for RMFSL. This study aimed to determine the underlying pathogenic mutations of a Chinese family with RMFSL and to confirm the effect of the splice-site mutation by reverse transcription analysis. METHODS: Detailed family history and clinical data were recorded, and peripheral blood samples were collected from all available family members. Whole exome sequencing (WES), Sanger sequencing, and bioinformatics analysis were performed to investigate the causative variants. The impact of the intronic variant on splicing was subsequently analyzed by RT-PCR analysis. RESULTS: We identified two compound heterozygous variants in the BRAT1, c.431-2A>G in intron 3 and c.1359_1361del(p.Leu454del) in exon 9 in the proband, one inherited from each parent. Furthermore, the 3'-splice site acceptor (c.431-2A>G) variant was found to activate a cryptic acceptor splice site, which resulted in the loss of 29 nucleotides and generation of a premature stop codon at code 180, producing a truncated BRAT1 (c.432_460del; p.Ala145Argfs*36). CONCLUSIONS: This research identified two mutations in the BRAT1 of one Chinese family with RMFSL. These data can aid in developing clinical diagnoses as well as providing genetic counseling and prenatal interventions to the family. These findings also expand our knowledge of the spectrum of BRAT1 pathogenic variants in RMFSL syndrome.

Pre-surgery HKA angle and WBL percentage are nearly perfectly correlated to the Miniaci angle when planning open wedge high tibial osteotomies.

PURPOSE: To investigate the conversion formulas between the Miniaci angle, pre-surgery parameters, and changes in pre-surgery parameters in open-wedge high tibial osteotomy (OWHTO), including hip-knee-ankle (HKA) angle, weight-bearing line (WBL) percentage, mechanical medial proximal tibial angle (mMPTA), ΔHKA angle, ΔWBL percentage, ΔmMPTA, and other parameters. METHODS: From January 2012 to December 2019, 247 lower limbs of 144 patients with medial unicompartmental knee osteoarthritis combined with proximal tibia vara were enrolled. Inclusion criteria were adults, medial unicompartmental knee osteoarthritis, Kellgren-Lawrence classification grade ≤ Ⅲ, mMPTA ≤85° and mechanical lateral distal femoral angle (mLDFA) is normal (85°-90°), and patella facing anterior in the bipedal standing position. Exclusion criteria were history of fracture, trauma, or orthopaedic surgery; developmental dysplasia of the hip or femoral head necrosis; femoral bowing deformity; deformity of the tibial shaft; and leg length discrepancy. Using standing whole-leg radiographs (WLRs), an OWHTO simulation was performed to determine the Miniaci angle by delivering the WBL to the Fujisawa point. The relationship of the Miniaci angle, the pre-surgery parameters, and the changes in pre-surgery parameters were analysed by spearman's correlation and linear regression analyses. The relationship between the post-surgery HKA angle and pre-surgery parameters was analysed by multiple linear regression model. RESULTS: The Miniaci angle showed a near perfect correlation with the pre-surgery HKA angle (y=-1.05x+192.10, r2=0.99), pre-surgery WBL percentage (y=-0.25x+15.14, r2=0.97), ΔHKA angle (y=1.04x-0.03, r2=1.00), ΔWBL percentage (y=0.25x-0.52, r2=0.97), and ΔmMPTA (y=1.04x-0.03, r2=1.00). The ΔHKA angle showed nearly perfect correlation with the ΔmMPTA (y=1.00x, r2=1.00), and ΔWBL percentage (y=0.24x-0.47, r2=0.97). CONCLUSIONS: The pre-surgery HKA angle, pre-surgery WBL percentage, ΔHKA angle, ΔWBL, and ΔmMPTA percentage are nearly perfectly correlated to the Miniaci angle, while the ΔmMPTA and ΔWBL percentage are nearly perfectly correlated to the ΔHKA angle. CLINICAL RELEVANCE: With the conversion formulas determined in the current study, surgeons can calculate the Miniaci angle based on the pre-surgery parameters without the assistance of digital software for complex surgical simulation. The Miniaci angle is closely related to the gap of the medial opening wedge. Based on the Miniaci angle and the depth of the osteotomy, surgeons can calculate the gap required prior to surgery using trigonometric functions and then simply measure the gap during surgery.

A novel cuproptosis-related gene signature of prognosis and immune microenvironment in head and neck squamous cell carcinoma cancer.

BACKGROUND: Cuproptosis is a novel form of cell death that is highly related to mitochondrial metabolism and mediated by protein lipoacetylation. This study systematically assessed the differential expression and genetic alterations of cuproptosis-related genes (CRGs) in head and neck squamous-cell carcinoma (HNSCC) and constructed CRG risk models to predict survival in patients with HNSCC. METHODS: We investigated the expression of 19 CRGs in HNSCC and noncancerous tissues, and the relationship between mutation load, immune infiltration, and clinical features was examined based on data from public databases. CRG risk models were constructed by univariate Cox analysis and lasso regression and validated by independent datasets for their accuracy in predicting survival outcomes in patients with HNSCC. The expression distribution of CRGs in HNSCC cells was further explored in the HNSCC single-cell sequencing dataset. RESULTS: NFE2L2, ATP7A, FDX1, LIAS, DLD, DLAT, PDHB, MTF1 and DBT were highly expressed in noncancerous samples, while GLS, CDKN2A and DLST were highly expressed in HNSCC samples (p < 0.05). Gene copy number variation frequency (CNV) revealed CDKN2A, FDX1 and DLAT copy number deletions and LIPT2 and NFE2L2 copy number increases. Ten CRGs were used to construct a risk model to predict overall survival (OS) in HNSCC, yielding reduced OS in the high-risk group compared to the low-risk group, training group (p = 9.733e - 05), and testing group (p = 0.040). The CRG risk model was significantly correlated with various immune cells, regulatory T cells (Tregs) and memory B cells were significantly negatively correlated (p = 0.027, p = 0.00084), and resting CD4 memory T cells was significantly positively correlated (p = 9e - 04). Most CRGs significantly affected the clinical characteristics of HNSCC. NFE2L2, SLC31A1, PDHA1, CDKN2A and DBT were highly expressed in epithelial cells of HNSCC, while SLC31A1, DBT and NFE2L2 were highly expressed in T cells, and SLC31A1 in B cells. In monocytes, NFE2L2, SLC31A1 and PDHA1 were highly expressed. CONCLUSION: The CRG risk model can be used as a potential prognostic factor for HNSCC patients and may provide new insights into cancer treatment from the perspective of copper metabolism.

Characteristics of sleep structure in Parkinson's disease patients with hallucinations based on polysomnography.

Hallucination is a common non-motor symptom in patients with Parkinson's disease (PD). Additionally, sleep disorders are associated with an increased risk of hallucinations in PD patients. This study aimed to examine the association between hallucination and objective sleep parameters in PD patients. We retrospectively recruited 278 PD patients who underwent polysomnography and clinical assessments and classified them into non-hallucination and hallucination groups. Hallucinations were observed in 77 older PD patients who had more severe motor symptoms and higher scores on the Non-Motor Symptoms Questionnaire (NMSQ), Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) but lower scores on the Montreal Cognitive Assessment (MOCA) and PD Sleep Scale (PDSS) than PD patients without hallucinations. Analysis of the polysomnographic variables in patients with hallucinations showed that they exhibited a decrease in total sleep time, sleep efficiency (SE), rapid eye movement (REM) sleep time and slow wave sleep (SWS, N3) time and percentage but a significant increase in wake time after sleep onset (WASO), periodic limb movement index (PLMI) scores, and stage 2 NREM (N2)percentage. Logistic regression analysis revealed that higher NMSQ scores, lower MOCA scores, lower SE, and a lower percentage of N3 sleep were associated with hallucinations in PD patients. Our results suggested that PD patients with hallucinations had worse sleep quality and differences in sleep architecture (measured by polysomnography).

Comprehensive analysis of T cell receptor repertoire in patients with KRAS mutant non-small cell lung cancer.

Background: Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes in non-small cell lung cancer (NSCLC). The administration of immunotherapy has demonstrated significant efficacy in prolonging the overall survival of patients with KRAS mutation in recent years. However, the efficacy of immunotherapy in KRAS mutant NSCLC is variable. Analysis of T cell receptor (TCR) repertoire may contribute to a better understanding of the mechanisms behind such differential outcomes. Methods: A total of 47 patients with KRAS mutant NSCLC were enrolled in this study. Deep sequencing of the TCR ß chain complementarity-determining regions in tumor tissue and paired peripheral blood specimens was conducted. Comprehensive analysis of TCR repertoire metrics was performed with different KRAS mutation subtypes and concomitant mutations. Moreover, the associations between TCR repertoire metrics and tumor mutation burden (TMB), as well as programmed death-ligand 1 were explored, respectively. Results: TCR repertoire metrics, including Shannon index, Clonality, and Morisita index (MOI), showed no significant differences among different KRAS mutation subtypes. The similar results were observed between patients with tumor protein p53 (TP53) mutation and those with wild-type TP53. In contrast, although no significant differences were found in Shannon index and Clonality, patients with KRAS/serine/threonine kinase 11 (STK11) comutation showed a significantly higher MOI compared to their STK11 wild-type counterparts (P=0.012). In addition, TCR repertoire metrics were neither associated with TMB nor programmed death-ligand 1 expression in KRAS mutant NSCLC. Conclusions: This retrospective study comprehensively described the TCR repertoire in KRAS mutant NSCLC. A higher MOI represented more overlap of the TCR repertoire between tumor tissue and paired peripheral blood, indicating distinctive immunological features in NSCLC with KRAS/STK11 comutation.