SMARCAL1 is a dual regulator of innate immune signaling and PD-L1 expression that promotes tumor immune evasion.

Genomic instability can trigger cancer-intrinsic innate immune responses that promote tumor rejection. However, cancer cells often evade these responses by overexpressing immune checkpoint regulators, such as PD-L1. Here, we identify the SNF2-family DNA translocase SMARCAL1 as a factor that favors tumor immune evasion by a dual mechanism involving both the suppression of innate immune signaling and the induction of PD-L1-mediated immune checkpoint responses. Mechanistically, SMARCAL1 limits endogenous DNA damage, thereby suppressing cGAS-STING-dependent signaling during cancer cell growth. Simultaneously, it cooperates with the AP-1 family member JUN to maintain chromatin accessibility at a PD-L1 transcriptional regulatory element, thereby promoting PD-L1 expression in cancer cells. SMARCAL1 loss hinders the ability of tumor cells to induce PD-L1 in response to genomic instability, enhances anti-tumor immune responses and sensitizes tumors to immune checkpoint blockade in a mouse melanoma model. Collectively, these studies uncover SMARCAL1 as a promising target for cancer immunotherapy.

From interaction networks to interfaces, scanning intrinsically disordered regions using AlphaFold2.

The revolution brought about by AlphaFold2 opens promising perspectives to unravel the complexity of protein-protein interaction networks. The analysis of interaction networks obtained from proteomics experiments does not systematically provide the delimitations of the interaction regions. This is of particular concern in the case of interactions mediated by intrinsically disordered regions, in which the interaction site is generally small. Using a dataset of protein-peptide complexes involving intrinsically disordered regions that are non-redundant with the structures used in AlphaFold2 training, we show that when using the full sequences of the proteins, AlphaFold2-Multimer only achieves 40% success rate in identifying the correct site and structure of the interface. By delineating the interaction region into fragments of decreasing size and combining different strategies for integrating evolutionary information, we manage to raise this success rate up to 90%. We obtain similar success rates using a much larger dataset of protein complexes taken from the ELM database. Beyond the correct identification of the interaction site, our study also explores specificity issues. We show the advantages and limitations of using the AlphaFold2 confidence score to discriminate between alternative binding partners, a task that can be particularly challenging in the case of small interaction motifs.

Left ventricular longitudinal strain in patients with type 2 diabetes mellitus is independently associated with glycated hemoglobin level.

OBJECTIVE: Left ventricular and left atrial strain are sensitive and reliable markers for evaluating cardiac function in patients with type 2 diabetes mellitus (T2DM), with interactions between the two parameters. The present study aimed to analyze the correlation between global longitudinal strain (GLS) of the left ventricle and glycated hemoglobin (HbA1c) levels in patients with T2DM. METHODS: A total of 292 patients clinically diagnosed with T2DM were selected and divided into three groups according to HbA1c level. The strains of the left atrium and left ventricle in the three groups of T2DM patients with different HbA1c levels were compared. Univariate and multivariate (including left atrial functional indicators) linear regression analyses were performed to assess the relationship between strain indicators and HbA1c levels. Generalized additive models were used to examine the relationship between strain indicators and HbA1c levels. RESULTS: There were significant differences among the three groups in terms of age, microalbuminuria, total cholesterol, fasting blood glucose, postprandial blood glucose, and HbA1c level, and left atrial conduit longitudinal strain (LAScd) and GLS (p < .05). Univariate and multivariate linear regression analyses revealed that, as HbA1c levels increased, the absolute value of GLS gradually decreased (p < .001). Curve fitting revealed a positive correlation between HbA1c level and GLS, which was not affected by left atrial function. CONCLUSION: Left ventricular GLS was independently correlated with HbA1c level in patients with T2DM and was not affected by left atrial function.

Application of ultrasound in preoperative localization diagnosis of checkrein deformity: A retrospective case series.

BACKGROUND: Checkrein deformity, is a rare claw toe dynamic deformity of the hallux or great toe. This study investigated the use of diagnostic ultrasound in positioning the accurate injury location causing checkrein deformity and its clinical significance for etiological diagnosis and selection of surgical methods. METHODS: This retrospective study included patients with confirmed checkrein deformities (according to typical symptoms) at the Department of Traumatic Orthopedics of Tianjin Hospital (Tianjin, China) from March 2017 to July 2021. RESULTS: A total of 11 patients (8 males and 3 females) with a mean age of 36.7 ± 16.8 (range 19-61) were included in this study. The injuries included six cases of tibia and fibula fracture, one case of single tibia fracture, and one case of single fibula fracture. Four patients were treated with steel plate internal fixation, three patients with intramedullary nailing, and one patient with external fixation. Three patients reported no history of any high-energy trauma or surgery. The ultrasound results showed that seven patients suffered from flexor hallucis longus (FHL) lesions, two patients suffered from flexor digitorum longus (FDL) lesions, and two patients suffered from FHL and FDL lesions. The patients underwent different surgeries tailored to their specific lesions. Toe flexion deformity was completely corrected after operation in all patients. The function of the toes was recovered to varying extent. CONCLUSION: The results of this study demonstrates that the checkrein deformities can be confirmed by ultrasound. It could be used to determine the adhesions before the operation, acting as guidance while establishing the surgical planning.

Evaluation of the electrocardiogram RV5 /V6 criteria in the diagnosis of left ventricular hypertrophy in marathon runners.

To assess the value of electrocardiogram (ECG) RV5/V6 criteria for diagnosing left ventricular hypertrophy (LVH) in marathons. A total of 112 marathon runners who met the requirements for "Class A1" events certified by the Chinese Athletics Association in Changzhou City were selected, and their general clinical information was collected. ECG examinations were performed using a Fukuda FX7402 Cardimax Comprehensive Electrocardiograph Automatic Analyser, whereas routine cardiac ultrasound examinations were performed using a Philips EPIQ 7C echocardiography system. Real-time 3-dimensional echocardiography (RT-3DE) was performed to acquire 3-dimensional images of the left ventricle and to calculate the left ventricular mass index (LVMI). According to the LVMI criteria of the American Society of Echocardiography for the diagnosis of LVH, the participants were divided into an LVMI normal group (n = 96) and an LVH group (n = 16). The correlation between the ECG RV5/V6 criteria and LVH in marathon runners was analysed using multiple linear regression stratified by sex and compared with the Cornell (SV3 + RaVL), modified Cornell (SD + RaVL), Sokolow-Lyon (SV1 + RV5/V6), Peguero-Lo Presti (SD + SV4), SV1, SV3, SV4, and SD criteria. In marathon runners, the ECG parameters SV3 + RaVL, SD + RaVL, SV1 + RV5/V6, SD + SV4, SV3, SD, and RV5/V6 were able to identify LVH (all p < .05). When stratified by sex, linear regression analysis revealed that a significantly higher number of ECG RV5/V6 criteria were evident in the LVH group than in the LVMI normal group (p < .05), both with no adjustment and after initial adjustment (including age and body mass index), as well as after full adjustment (including age, body mass index, interventricular septal thickness, left ventricular end-diastolic diameter, left ventricular posterior wall thickness, and history of hypertension). Additionally, curve fitting showed that the ECG RV5/V6 values increased with increasing LVMI in marathon runners, exhibiting a nearly linear positive correlation. In conclusions, the ECG RV5/V6 criteria were correlated with LVH in marathon runners.

Diagnostic accuracy of multiparametric ultrasound for peripheral nerve schwannoma.

BACKGROUND: Ultrasound (US) diagnostic techniques have the advantages of low cost, convenient operation, and high availability. PURPOSE: To explore the diagnostic accuracy of multiparametric US in evaluating signs of peripheral schwannoma. MATERIAL AND METHODS: This retrospective case-control study included patients with soft-tissue masses on the limbs (divided into the schwannoma and non-schwannoma groups) between January 2017 and November 2020. US features were compared between the two groups, and receiver operating characteristics analysis was used to evaluate the diagnostic efficacy of these features. RESULTS: A total of 165 patients were included in this study; of them, 63 (38.2%) were diagnosed with schwannoma. Regular morphology (95.2% vs. 39.2%), cystic degeneration (71.4% vs. 27.5%), target sign on elastography (82.5% vs. 0), and polar blood supply sign (87.3% vs. 14.7%) were more common in schwannomas than in non-schwannoma lesions (all P < 0.001). Combining the four signs for diagnosis of schwannomas, the sensitivity, specificity, and accuracy were 95.24%, 96.08%, and 95.76%, respectively, with an area under the curve (AUC) of 0.987 (95% confidence interval = 0.955-0.998). Entering and exiting nerve sign was observed in 87.3% of schwannomas and in 3.0% of non-schwannoma lesions (P < 0.001), while split-fat sign was similar between the two groups (9.5% vs. 2.0%; P = 0.068). CONCLUSION: Polar blood supply sign and target sign on elastography are specific US signs in peripheral schwannomas. The combination of two-dimensional imaging, color flow imaging, and elastography can achieve an excellent diagnostic accuracy in schwannomas.

Morphological Changes of Medial Epicondyle-Olecranon Ligament and Ulnar Nerve in the Cubital Tunnel Syndrome: An Ultrasonic Study.

OBJECTIVE: Few studies have performed detailed ultrasound measurements of medial epicondyle-olecranon (MEO) ligament that cause the entrapment of ulnar nerve. This study aims to comprehensively evaluate dynamic ultrasonographic characteristics of MEO ligament and ulnar nerve for clinical diagnosis and accurate treatment of cubital tunnel syndrome (CuTS). METHODS: Thirty CuTS patients (CuTS group) and sixteen healthy volunteers (control group) who underwent ultrasound scanning from October 2016 to October 2020 were retrospectively collected, with 30 elbows in each group. Primary outcomes were thickness at six points, length and width of MEO ligament. Secondary outcomes were thickness of ulnar nerve under MEO ligament at seven parts and the cross-sectional area (CSA) of ulnar nerve at proximal end of MEO ligament (P0 mm ). The thickness of MEO ligament and ulnar nerve in different points of each group was compared by one-way ANOVA analysis with Bonferroni post hoc test, other outcomes were compared between two elbow positions or two groups using independent-samples t test. RESULTS: Thickness of MEO ligament in CuTS group at epicondyle end, midpoint in transverse view, olecranon end, proximal end, midpoint in axial view, and distal end was 0.67 ± 0.31, 0.37 ± 0.18, 0.89 ± 0.35, 0.39 ± 0.21, 0.51 ± 0.38, 0.36 ± 0.25 at elbow extension, 0.68 ± 0.34, 0.38 ± 0.27, 0.77 ± 0.39, 0.32 ± 0.20, 0.48 ± 0.22, 0.32 ± 0.12 (mm) at elbow flexion, respectively. Compared with control group, they were significantly thickened except for proximal end at elbow flexion. MEO ligament thickness at epicondyle end and olecranon end was significantly larger than midpoint in two groups. No significant difference was found in length and width of MEO ligament among different comparisons. Ulnar nerve thickness at 5 mm proximal to MEO ligament (P5 mm , 3.25 ± 0.66 mm) was significantly increased than midpoint of MEO ligament (Mid), distal end of MEO ligament (D0 mm ), 5 mm (D5 mm ), 10 mm (D10 mm ) distal to MEO ligament at extension in CuTS group. Compared with control group, ulnar nerve thickness at P5 mm in CuTS group was significantly increased at extension position, at D5 mm and D10 mm was significantly decreased at flexion position. CSA of ulnar nerve at extension position (14.44 ± 4.65 mm2 ) was significantly larger than flexion position (11.83 ± 3.66 mm2 ) in CuTS group, and CuTS group was significantly larger than control group at two positions. CONCLUSIONS: MEO ligament in CuTS patients was thickened, which compressed ulnar nerve and caused its proximal end swelling. Ultrasonic image of MEO ligament thickness was a significant indicator for CuTS and can guide surgeons in selecting the appropriate treatment.

Pi-Dan-Jian-Qing Decoction Ameliorates Type 2 Diabetes Mellitus Through Regulating the Gut Microbiota and Serum Metabolism.

Pi-Dan-Jian-Qing decoction (PDJQ) can been used in the treatment of type 2 diabetes mellitus (T2DM) in clinic. However, the protective mechanisms of PDJQ on T2DM remain unknown. Recent studies have shown that the changes in gut microbiota could affect the host metabolism and contribute to progression of T2DM. In this study, we first investigated the therapeutic effects of PDJQ on T2DM rats. 16S rRNA sequencing and untargeted metabolomics analyses were used to investigate the mechanisms of action of PDJQ in the treatment of T2DM. Our results showed that PDJQ treatment could improve the hyperglycemia, hyperlipidemia, insulin resistance (IR) and pathological changes of liver, pancreas, kidney, and colon in T2DM rats. PDJQ could also decrease the levels of pro-inflammatory cytokines and inhibit the oxidative stress. 16S rRNA sequencing showed that PDJQ could decrease the Firmicutes/Bacteroidetes (F to B) ratio at the phylum level. At the genus level, PDJQ could increase the relative abundances of Lactobacillus, Blautia, Bacteroides, Desulfovibrio and Akkermansia and decrease the relative abundance of Prevotella. Serum untargeted metabolomics analysis showed that PDJQ could regulate tryptophan metabolism, histidine metabolism, tricarboxylic acid (TCA) cycle, phenylalanine, tyrosine and tryptophan biosynthesis and tyrosine metabolism pathways. Correlation analysis indicated that the modulatory effects of PDJQ on the tryptophan metabolism, histidine metabolism and TCA cycle pathways were related to alterations in the abundance of Lactobacillus, Bacteroides and Akkermansia. In conclusion, our study revealed the various ameliorative effects of PDJQ on T2DM, including improving the liver and kidney functions and alleviating the hyperglycemia, hyperlipidemia, IR, pathological changes, oxidative stress and inflammatory response. The mechanisms of PDJQ on T2DM are likely linked to an improvement in the dysbiosis of gut microbiota and modulation of tryptophan metabolism, histamine metabolism, and the TCA cycle.

Jian-Gan-Xiao-Zhi Decoction Alleviates Inflammatory Response in Nonalcoholic Fatty Liver Disease Model Rats through Modulating Gut Microbiota.

BACKGROUND: Jian-Gan-Xiao-Zhi decoction (JGXZ), composed of Salvia miltiorrhiza Bunge, Panax notoginseng, Curcuma zedoaria, and other 9 types of herbs, has demonstrated beneficial effects on nonalcoholic fatty liver disease (NAFLD). However, the mechanisms behind JGXZ's impact on NAFLD remain unknown. METHODS: In this study, a NAFLD rat model induced by a high-fat diet (HFD) received oral treatment of JGXZ (8 or 16 g crude herb/kg) for 12 weeks. The therapeutic effects of JGXZ on NAFLD model rats were investigated through blood lipid levels and pathological liver changes. 16S rRNA analysis was used to study the changes in gut microbiota after JGXZ treatment. The expressions of occludin and tight junction protein 1 (ZO-1) in the colon were investigated using immunostaining to study the effects of JGXZ on gut permeability. The anti-inflammatory effects of JGXZ were also studied through measuring the levels of IL-1ß, IL-6, and TNF-α in the serum and liver. RESULTS: JGXZ treatment could decrease body weight and ameliorate dyslipidemia in NAFLD model rats. H&E and Oil Red O staining indicated that JGXZ reduced steatosis and infiltration of inflammatory cells in the liver. 16S rRNA analysis showed that JGXZ impacted the diversity of gut microbiota, decreasing the Firmicutes-to-Bacteroidetes ratio, and increasing the relative abundance of probiotics, such as Alloprevotella, Lactobacillus, and Turicibacter. Gut permeability evaluation found that the expressions of ZO-1 and occludin in the colon were increased after JGXZ treatment. Moreover, JGXZ treatment could decrease the levels of IL-1ß, IL-6, and TNF-α in the serum and liver. CONCLUSIONS: Our study illustrated that JGXZ could ameliorate NAFLD through modulating gut microbiota, decreasing gut permeability, and alleviating inflammatory response.

Ultrasound-Assisted Precise In Situ Decompression for Cubital Tunnel Syndrome.

OBJECTIVE: To explore the effect of locating the ulnar nerve compression sites and guiding the small incision so as to decompress the ulnar nerve in situ on the elbow by high-frequency ultrasound before operation. METHODS: A retrospective analysis was conducted on 56 patients who underwent ultrasound-assisted in situ decompression for cubital tunnel syndrome from May 2018 to August 2019. The patients' average age was 51.13 ± 7.35 years, mean duration of symptoms was 6.51 ± 1.96 months, and mean postoperative follow-up was 6.07 ± 0.82 months. Nine patients had Dellon's stage mild, 39 had stage moderate, and eight had stage severe. Ultrasound and electromyography were completed in all patients before operation. The presence of ulnar nerve compressive lesion, the specific location, and the reason and extent of compression were determined by ultrasound. A small incision in situ surgery was given to decompress the ulnar nerve according to the pre-defined compressive sites. RESULTS: All patients underwent in situ decompression. The compression sites around the elbow were as follows: two in the arcade of Struthers, one in the medial intermuscular septum, four in the anconeus epitrochlearis muscle, five beside the cyst of the proximal flexor carpi ulnaris (FCU), and the remaining 44 cases were all from the compression between Osborne's ligament to the two heads of the FCU. The compression localizations diagnosed by ultrasound were confirmed by operations. Preoperative ultrasound confirmed no ulnar nerve subluxation in all cases. The postoperative outcomes were satisfactory. There was no recurrence or aggravation of symptoms in this group of patients according to the modified Bishop scoring system; results showed that 43 cases were excellent, 10 were good, and three were fair. CONCLUSIONS: High-frequency ultrasound can accurately and comprehensively evaluate the ulnar nerve compression and the surrounding tissues, thus providing significant guidance for the precise minimally invasive treatment of ulnar nerve compression.

Molecular, crystal and physicochemical properties of granular waxy corn starch after repeated freeze-thaw cycles at different freezing temperatures.

The study was undertaken to reveal the effects of freeze-thaw cycles at different freeze temperature (-20 °C, -40 °C and -80 °C) and the number of freeze-thaw cycles (3, 6, 12, 18, 24 times) on physicochemical and structural properties of waxy corn starch. The number of pores on the surface of starch granules increased, but there was no significant (P < 0.05) effect on molecular weight, transparency, freeze-thaw stability and the crystal structure of starch after repeated freeze-thaw cycle. But the crystallinity intensity decreased after freeze-thaw cycles treatment and a tiny decrease in onset, peak, conclusion temperature and gelatinization enthalpy were found. The RVA analysis exhibited an increase in gelatinization temperatures and a decrease in breakdown and setback value after freeze-thaw treatment, which manifested an increase in the aging and heat resistance of waxy corn starch paste. However, there was no statistical (P < 0.05) difference between different freeze temperatures at the same number of freeze-thaw cycle on physicochemical and structural properties of starch. The obtained data could be helpful in evaluation of the repeated freeze-thaw treatment of waxy corn starch-based foodstuffs and providing the theoretical basic for revealing the effect of repeated freeze-thaw processes in manufacture applications.

An amperometric immunosensor based on multi-walled carbon nanotubes-thionine-chitosan nanocomposite film for chlorpyrifos detection.

In this work, a novel amperometric immunosensor based on multi-walled carbon nanotubes-thionine-chitosan (MWCNTs-THI-CHIT) nanocomposite film as electrode modified material was developed for the detection of chlorpyrifos residues. The nanocomposite film was dropped onto a glassy carbon electrode (GCE), and then the anti-chlorpyrifos monoclonal antibody was covalently immobilized onto the surface of MWCNTs-THI-CHIT/GCE using the crosslinking agent glutaraldehyde (GA). The modification procedure was characterized by using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Under the optimized conditions, a linear relationship between the relative change in peak current of different pulse voltammetry (DPV) and the logarithm of chlorpyrifos solution concentration was obtained in the range from 0.1 to 1.0 × 10(5) ng/mL with a detection limit of 0.046 ng/mL. The proposed chlorpyrifos immunosensor exhibited high reproducibility, stability, and good selectivity and regeneration, making it a potential alternative tool for ultrasensitive detection of chlorpyrifos residues in vegetables and fruits.

Signet-ring cell carcinoma of ampulla of Vater: contrast-enhanced ultrasound findings.

Signet-ring cell carcinoma (SRCC) of ampulla of Vater is extremely uncommon, and less than 15 cases have been reported so far in literature. It mainly occurs in elderly people (median age 57 years). We report a rare case of SRCC of the ampulla of Vater in a 38-year-old woman who presented with a small tumor at the Vater, discovered by the contrast-enhanced ultrasound (CEUS). Histopathological examination showed prominent signet-ring features. We also describe the imaging features of SRCC of ampulla of Vater in CEUS.