Discovery of a Novel and Potent LCK Inhibitor for Leukemia Treatment via Deep Learning and Molecular Docking.

The lymphocyte-specific protein tyrosine kinase (LCK) plays a crucial role in both T-cell development and activation. Dysregulation of LCK signaling has been demonstrated to drive the oncogenesis of T-cell acute lymphoblastic leukemia (T-ALL), thus providing a therapeutic target for leukemia treatment. In this study, we introduced a sophisticated virtual screening strategy combined with biological evaluations to discover potent LCK inhibitors. Our initial approach involved utilizing the PLANET algorithm to assess and contrast various scoring methodologies suitable for LCK inhibitor screening. After effectively evaluating PLANET, we progressed to devise a virtual screening workflow that synergistically combines the strengths of PLANET with the capabilities of Schrödinger's suite. This integrative strategy led to the efficient identification of four potential LCK inhibitors. Among them, compound 1232030-35-1 stood out as the most promising candidate with an IC50 of 0.43 nM. Further in vitro bioassays revealed that 1232030-35-1 exhibited robust antiproliferative effects on T-ALL cells, which was attributed to its ability to suppress the phosphorylations of key molecules in the LCK signaling pathway. More importantly, 1232030-35-1 treatment demonstrated profound in vivo antileukemia efficacy in a human T-ALL xenograft model. In addition, complementary molecular dynamics simulations provided deeper insight into the binding kinetics between 1232030-35-1 and LCK, highlighting the formation of a hydrogen bond with Met319. Collectively, our study established a robust and effective screening strategy that integrates AI-driven and conventional methodologies for the identification of LCK inhibitors, positioning 1232030-35-1 as a highly promising and novel drug-like candidate for potential applications in treating T-ALL.

[Comparison of open reduction hollow nail anchoring system with loop plate fixation under arthroscopy for the treatment of posterior cruciate ligament avulsion fractures].

OBJECTIVE: To compare clinical effect between open reduction and fixation with cannulated screw and threaded rivet via posteromedial approach versus arthroscopic Endobutton plate fixation in treating posterior cruciate ligament avulsion fractures. METHODS: Clinical data of 38 patients with posterior cruciate ligament avulsion fractures from July 2020 to December 2021 were analyzed retrospectively, and divided into open reduction and internal fixation group (posterior medial approach hollow anchor system fixation) and arthroscopic fixation group (Endobutton with loop plate fixation under arthroscopy). There were 20 patients in open reduction and internal fixation group, including 16 males and 4 females, aged from 26 to 74 years old with an average of (42.9±18.8) years old;13 patients on the left side and 7 patients on the right side;12 patients were classified to typeⅡand 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;14 patients were gradeⅡand 6 patients were grade Ⅲ in back drawer test. There were 18 patients in arthroscopic fixation group, including 11 males and 7 females;aged from 24 to 70 years old with an average of (53.5±13.4) years old;11 patients on the left side and 7 patients on the right side;10 patients were classified to typeⅡand 8 patiens with type Ⅲ according to Meyers-McKeever fractures classification;11 patients were gradeⅡand 7 patients were grade Ⅲ in back drawer test. Operation time, blood loss, and quality of immediate reduction were compared between two groups. Knee range of motion, knee back drawer test, and International Knee Documentation Committee(IKDC) grading, KT2000 stability evaluation and Lysholm function score of knee joint were compared at 6 months after operation. RESULTS: All patients were followed up for 8 to 16 months with an average of (12.3±1.9) months. There were no complications such as incision infection, fracture malunion or non-union, and internal fixation loosening occurred. The avulsion fractures of knee joint were reached to imaging healing standard at 6 months after operation. Operation time and blood loss in open reduction and internal fixation group were (56.4±7.1) min and (63.2±10.2) ml, while (89.9±7.4) min and (27.7±8.7) ml in arthroscopic fixation group, respectively, and had significant difference between two groups (P<0.05). There were no differences in immediate reduction quality (χ2=0.257, P=0.612), knee joint range of motion at 6 months after opertaion (t=0.492, P=0.626), knee joint rear drawer test ( χ2=0.320, P=0.572), IKDC classification of knee joint (χ2=0.127, P=0.938), KT2000 stability evaluation (χ2=0.070, P=0.791), and knee Lysholm function score (t=0.092, P=0.282) between two groups. CONCLUSION: Posterior medial approach with hollow anchoring system fixation and arthroscopic Endobutton with loop plate fixation for the treatment of posterior cruciate ligament tibial occlusion avulsion fracture could achieve satisfactory clinical results, and arthroscopic surgery has less bleeding, but also has a longer learning curve and longer operation time than traditional incision surgery. The surgeon needs to make a choice according to clinical situation of patient and their own surgical inclination.

Bioaccumulation and Male Reproductive Toxicity of the New Brominated Flame Retardant Tetrabromobisphenol A-Bis(2,3-dibromo-2-methylpropyl ether) in Comparison with Hexabromocyclododecane.

Tetrabromobisphenol A-bis(2,3-dibromo-2-methylpropyl ether) (TBBPA-DBMPE) has come into use as an alternative to hexabromocyclododecane (HBCD), but it is unclear whether TBBPA-DBMPE has less hazard than HBCD. Here, we compared the bioaccumulation and male reproductive toxicity between TBBPA-DBMPE and HBCD in mice following long-term oral exposure after birth. We found that the concentrations of TBBPA-DBMPE in livers significantly increased with time, exhibiting a bioaccumulation potency not substantially different from HBCD. Lactational exposure to 1000 µg/kg/d TBBPA-DBMPE as well as 50 µg/kg/d HBCD inhibited testis development in suckling pups, and extended exposure up to adulthood resulted in significant molecular and cellular alterations in testes, with slighter effects of 50 µg/kg/d TBBPA-DBMPE. When exposure was extended to 8 month age, severe reproductive impairments including reduced sperm count, increased abnormal sperm, and subfertility occurred in all treated animals, although 50 µg/kg/d TBBPA-DBMPE exerted lower effects than 50 µg/kg/d HBCD. Altogether, all data led us to conclude that TBBPA-DBMPE exerted weaker male reproductive toxicity than HBCD at the same doses but exhibited bioaccumulation potential roughly equivalent to HBCD. Our study fills the data gap regarding the bioaccumulation and toxicity of TBBPA-DBMPE and raises concerns about its use as an alternative to HBCD.

Hydraulic conductivity and microscopic properties of polyanionic cellulose and microscale zero-valent iron amended sand/bentonite backfills exposed to dichloromethane solution.

Leachate comprising organic contaminants such as dichloromethane is frequently discharged into groundwater at contaminated sites and unlined landfills. Soil-bentonite backfills in vertical cutoff walls are extensively employed to contain the flow of contaminated groundwater, thereby safeguarding the downstream groundwater environmental quality and ecosystem. This study presented a comprehensive evaluation of effects of dichloromethane-impacted groundwater on hydraulic conductivity and microscopic characteristics of soil-bentonite backfills amended with polymer namely polyanionic cellulose and microscale zero-valent iron. The results showed the amended backfills exhibited lower hydraulic conductivity than the unamended backfill regardless of the permeant type, i.e., tap water and dichloromethane solution. Scanning electron microscopy coupled with energy-dispersive spectrometry analyses demonstrated that polyanionic cellulose hydrogel could effectively coat sand, bentonite, and microscale zero-valent iron particles, providing protection of bentonite particles against attacks imposed by the dichloromethane and multivalent iron ions, and diminish aggregation of microscale zero-valent iron particles in the amended backfills. X-ray diffraction results indicated there was no intercalation of polyanionic cellulose and microscale zero-valent iron into the montmorillonite platelets of bentonite particles. Based on the Fourier Transform Infrared Spectroscopy Spectra analysis, a new functional group (-CH2) was identified on the polyanionic cellulose amended bentonite particles. The results demonstrated that amendment with polyanionic cellulose and microscale zero-valent iron is a promising approach to improve the performance of soil-bentonite backfills in containing flow of dichloromethane-impacted groundwater.

Left Ventricular Pressure Strain Loops for Evaluation of Myocardial Work in Type 2 Diabetic Patients with Hypertension.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and hypertension (HT) are the two most common underlying diseases worldwide, and they often coexist. The long-term existence of both may lead to left ventricular dysfunction. Therefore, evaluating the cardiac function of T2DM patients with HT is vital to guide treatment and improve prognosis. Left ventricular pressure strain loops (LVPSL) combine left ventricular strain and afterload, which can quantify left ventricular energy expenditure and detect left ventricular subclinical systolic dysfunction. Many studies have focused on myocardial work (MW) in uncomplicated T2DM patients or simple HT patients, but a few have focused on T2DM patients with HT. OBJECTIVE: The study aimed to evaluate the MW changes in T2DM patients with HT using LVPSL and to find independent related factors of MW parameters. METHODS: 40 T2DM patients, 35 HT patients, 40 T2DM patients with HT (T2DM+HT group), and 35 controls were enrolled. The differences between clinical data, conventional ultrasound parameters, and MW parameters were analyzed among the four groups. RESULTS: The global longitudinal strain (GLS) of the T2DM group, HT group, and T2DM+HT group was lower than the control group (P<0.05). The global work index (GWI) and global constructive work (GCW) in the T2DM group were lower than other groups (P<0.05). The GWI of the HT group was higher than other groups (P<0.05), while GCW was only higher than the T2DM group and T2DM+HT group (P<0.05). The GWI and GCW of the T2DM+HT group were higher than the T2DM group and were lower than the HT group(P<0.05), while there was no significant difference with the control group. HT group and T2DM+HT group had higher global work waste (GWW) (P<0.05). The global work efficiency (GWE) of the T2DM+HT group was lower than other groups (P<0.05). Systolic blood pressure (SBP) and glycosylated hemoglobin (HbA1c) were independent factors of each MW parameter. CONCLUSION: LVPSL can recognize left ventricular subclinical systolic dysfunction early in patients with T2DM and HT. Compared to simple T2DM or HT, the combination of T2DM and HT had greater damage to left ventricular systolic function. SBP and HbA1c are two factors that have a considerable impact on MW parameters. The impact of afterload on MW parameters should be paid more attention to.

Tunable Synthesis of Monofluoroalkenes and Gem-Difluoroalkenes via Solvent-Controlled Rhodium-Catalyzed Arylation of 1-Bromo-2,2-difluoroethylene.

Divergent synthesis of fluorine-containing scaffolds starting from a suite of raw materials is an intriguing topic. Herein, we report the solvent-controlled rhodium-catalyzed tunable arylation of 1-bromo-2,2-difluoroethylene. The selection of the reaction solvents provides switchable defluorinated or debrominated arylation from readily available feedstock resources (both arylboronic acids/esters and 1-bromo-2,2-difluoroethylene are commercially available). This switch is feasible because of the difference in coordination ability between the solvent (CH2 Cl2 or CH3 CN) and the rhodium center, resulting in different olefin insertion. This protocol allows the convenient synthesis of monofluoroalkenes and gem-difluoroalkenes, both of which are important scaffolds in the fields of medicine and materials. Moreover, this newly developed solvent-regulated reaction system can be applied to the site-selective dechlorinated arylation of trichloroethylene. Overall, this study provides a useful strategy for the divergent synthesis of fluorine-containing scaffolds and provides insight into the importance of solvent selection in catalytic reactions.

Are the recently described fossil Mole Crickets of Myanmar amber real gryllotalpids? (Orthoptera: Gryllotalpidae & Gryllidae).

We report five new Myanmar amber specimens attributable to "Mole Cricket" †Pherodactylus rectanguli n. comb., hitherto regarded as a Mole Cricket (Orthoptera: Grylloptalpidae). The new material includes two adult males, two adult females, and one nymph. The specimens are redescribed, and additional new characters are provided for their delimitation and corresponding species identification. We carry out a comparison between these new specimens with other taxa of mole crickets from Myanmar amber and extant true crickets. The result indicates that some species merely represent different nymphal development stages or adults of †Pherodactylus rectanguli n. comb., however, they were misidentified as different species. We also treated genera †Tresdigitus n. syn. and †Chunxiania n. syn. as synonyms of genus †Pherodactylus Poinar, Su & Brown, 2020, and treat †Tresdigitus gracilis Jiang, Xu, Jarzembowski & Xiao, 2022 n. syn. and †Chunxiania fania n. syn. as synonyms of †Pherodactylus rectanguli n. comb. †Burmagryllotalpa longa is valid, because its shape of the pronotum curved without lateral carinae. The morphological convergences and specializations of subterranean dwelling species are discussed. The robust fore tibia and long apical spurs of †P. micromorphus, †P. rectanguli n. comb. and †B. longa are insufficient evidence for an assignment to the family Gryllotalpidae. Instead, we suggest place them into the subfamily Gryllinae (Gryllidae), tribe Sclerogryllini, and group them into their own subtribe Pherodactylina n. subtr.. A key to the identification of recent and fossil Sclerogryllini is also provided. Their taxonomy and morphology are discussed.

Apolipoprotein A1 is associated with osteocalcin and bone mineral density rather than high-density lipoprotein cholesterol in Chinese postmenopausal women with type 2 diabetes mellitus.

Objective: Disturbances in high-density lipoprotein cholesterol (HDL-c) metabolic pathways can affect bone metabolism, which may rely on the particle function of apolipoprotein rather than HDL-c levels. This study aimed to evaluate the correlation of serum HDL-c and apolipoprotein A1 (APOA1) with bone metabolism in Chinese postmenopausal women with type 2 diabetes mellitus (T2DM). Method: A total of 1,053 participants with complete data were enrolled and separated into three groups based on the HDL-c and APOA1 tertiles. The trained reviewer collected demographic and anthropometric information. Bone turnover markers (BTMs) were determined by standard methods. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry. Results: Overall, the prevalence of osteoporosis was 29.7%. Groups with higher APOA1 have a remarkably more elevated level of osteocalcin (OC), L1-L4 BMD, and T-score across the APOA1 tertiles. APOA1 presented a positive correlation with OC (r = 0.194, p < 0.001), L1-L4 BMD (r = 0.165, p < 0.001), and T-score (r = 0.153, p < 0.001) rather than HDL-c. Meanwhile, APOA1 remained independently associated with OC (ß = 0.126, p < 0.001), L1-L4 BMD (ß = 0.181, p < 0.001), and T-score (ß = 0.180, p < 0.001) after adjustment for confounding factors. APOA1 is also shown to be independently correlated with osteoporosis after adjustment for confounding factors, and the OR (95%CI) was 0.851 (0.784-0.924). In contrast, there was no significant association between HDL-c and osteoporosis. Furthermore, APOA1 seemed to have the largest areas under the curve (AUC) for osteoporosis. The AUC (95% CI) of APOA1 identifying osteoporosis was 0.615 (0.577-0.652). The optimal cut-off value of APOA1 was 0.89 g/L (sensitivity: 56.5%, specificity: 67.9%). Conclusion: APOA1 is independently associated with OC, L1-L4 BMD, and osteoporosis rather than HDL-c in Chinese postmenopausal women with T2DM.

Evaluation of Head and Cervical Spine Posture after Therapy with Maxillary Protraction Appliances / Evaluación de la Postura de la Cabeza y la Columna Cervical Después de la Terapia con Aparatos de Protracción Maxilar

SUMMARY: The objective of this study was to evaluate the changes of head and cervical spine posture of skeletal class malocclusion in adolescent with maxillary protraction. Thirty cases of skeletal class malocclusion were randomly selected from the Stomatological Hospital of Shanxi Medical University. High-quality lateral cephalograms were collected including pre- and posttreatment to compare the changes of head and cervical spine posture. Data were processed using SPSS 26.0 statistical software. The paired-t test was used to compare pre- and posttreatment mean angular measurements.A significant difference in the SNA(p<0.001), SNB(p<0.01), and ANB(p<0.001) between T1 and T2 showed an improvement in the sagittal relationships. A significant change was observed in middle cervical spine posture, while upper cervical spine posture variables showed no significant difference after treatment. Skeletal class with maxillary protraction appliance not only led to the improvement of sagittal relationship, but also changed the middle cervical spine posture.

El objetivo de este estudio fue evaluar los cambios en la postura de la cabeza y la columna cervical debido a la maloclusión clase esquelética en adolescentes con protracción maxilar. Treinta casos de maloclusión de clase esquelética fueron seleccionados al azar del Hospital Estomatológico de la Universidad Médica de Shanxi. Se recogieron cefalogramas laterales de alta calidad, incluidos el tratamiento previo y posterior, para comparar los cambios en la postura de la cabeza y la columna cervical. Los datos se procesaron con el software estadístico SPSS 26.0. Se utilizó la prueba t pareada para comparar las medidas angulares medias antes y después del tratamiento. Una diferencia significativa en SNA (p <0,001), SNB (p <0,01) y ANB (p <0,001) entre T1 y T2 mostró una mejora en las relaciones sagitales. Se observó un cambio significativo en la postura de la columna cervical media, mientras que las variables de postura de la columna cervical superior no mostraron diferencias significativas después del tratamiento. La clase esquelética con aparato de protracción maxilar no solo condujo a la mejora de la relación sagital, sino que también cambió la postura de la columna cervical media.

Finite element analysis of tooth movement under different retraction force and intrusive force in double-archwire lingual orthodontics system.

The objectives of this study were to evaluate the tooth movement tendency during space closure in maxillary anterior teeth by various combinations of retraction force and intrusive force in a double-archwire lingual orthodontic system. Mini-implant-double slot lingual orthodontics system models of the bilateral maxillary first premolar extraction cases were constructed. Three-dimensional finite element models of the maxilla were constructed with definite position mini-implants (8 mm) and power arms (6 mm). Different retraction forces(50gf、100gf、150gf)were applied with the help of a nickel-titanium closed coil spring on the plate side. Intrusive forces(0gf、50gf、100gf)were applied with the help of the mini-implant between the two central incisors, and the initial displacements of the maxillary anterior teeth were analyzed. Variable amounts of displacements like controlled tipping, uncontrolled tipping, lingual crown tipping, labial root tipping, extrusion and distal crown tipping were observed in all the models, and these tendencies increased as the magnitude of retraction force increased, and these tendencies decreased as the magnitude of intrusive force increased. When the intrusive force was greater than or equal to the retraction force, the maxillary central incisors showed the trend of lingual crown tipping and labial root tipping, resulting in uncontrolled tipping movement. In terms of horizontal changes, the increasing width of bilateral anterior teeth was observed, with canines showing the least increasing trend. Various combinations of retraction force and intrusive force in a double-archwire lingual orthodontic system provide a new choice for torque control of the anterior teeth. Although anterior mini-implants and elastics can achieve incisor intrusion and lingual root torque, they cannot achieve the expected torque without additional torque control methods.

Effect of fermentation on structural properties and antioxidant activity of wheat gluten by Bacillus subtilis.

Bacillus subtilis has been extensively studied for its ability to inhibit the growth of harmful microorganisms and its high protease activity. In this study, Bacillus subtilis was used to ferment gluten and assess the effects of the fermentation process on the physicochemical, microstructure and antioxidant properties of gluten. The results of Fourier infrared spectroscopy (FT-IR) and circular chromatography (CD) showed a significant decrease in the content of α-helix structures and a significant increase in the content of ß-sheet structures in gluten after fermentation (p < 0.05). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that glutenin was degraded into small molecular peptides with a molecular weight of less than 26 kDa after 24 h of fermentation; meanwhile, the fermentation process significantly increased the free amino acid content of the samples (p < 0.05), reaching 1923.38 µg/mL at 120 h of fermentation, which was 39.46 times higher than that at 24 h of fermentation (p < 0.05). In addition, the fermented back gluten has higher free radical scavenging activity and iron reduction capacity. Therefore, fermented gluten may be used as a functional food to alleviate oxidative stress. This study provides a reference for the high-value application of gluten.

Altered functional activity in the right superior temporal gyrus in patients with definite vestibular migraine.

BACKGROUND: Vestibular migraine (VM) is one of the most common causes of episodic central vestibular disorders; it is worth investigating whether VM belongs to the migraine subtype or is a separate disorder. The study is aimed at investigating resting-state functional brain activity alterations in patients with definite VM (dVM). METHODS: Seventeen patients with dVM, 8 patients with migraine, and 17 health controls (HCs) were recruited. The amplitude of low frequency fluctuation (ALFF), fractional ALFF (fALFF), and regional homogeneity (ReHo) were calculated to observe the changes in spontaneous brain activity. RESULTS: Compared with HCs, VM patients showed significantly increased ALFF values in the right temporal lobe (P = 0.002) and increased ReHo values in the right superior, middle, and inferior temporal gyrus (STG, MTG, and ITG, P = 0.013); patients with migraine showed significantly increased ALFF values in the right limbic lobe (P = 0.04), left ITG (P = 0.024), and right frontal lobe (P < 0.001), significantly decreased ALFF values in the pons and brainstem (P = 0.013), and significantly decreased ReHo values in the frontal cortex (P < 0.001). Compared with patients with migraine, VM patients showed significantly increased fALFF values in the right parietal lobe (P = 0.011) and right frontal lobe (P = 0.026) and significantly increased ReHo values in the right thalamus (P = 0.043). CONCLUSIONS: Patients with VM and migraine both had altered brain function, but the regions involved are different.

Two new species of the genus Diestramima from China (Orthoptera: Rhaphidophoridae: Aemodogryllinae).

The genus Diestramima comprises 41 species from Asia with 31 species distributed in China. In this study, we reconstruct the phylogeny tree of Diestramima species by maximum likelihood and Bayesian inference based on three mitochondrial genes (COI, 12S and 16S). The result indicates that the phylogenetic results are coherent with that based on five molecular markers (COI, 12S, 16S, 18S and 28S). Moreover, two new species, D. pingmengensis sp. nov. He & Zong and D. gulinjingensis. sp. nov. Zong & He are described. Their validities are also supported by morphological features. Furthermore, D. sichuanensis Zhu & Shi, 2022 is treated as a junior synonym of D. guangxiensis Qin, Wang, Liu & Li, 2016 based on both morphological and molecular features.

Clinical Significance of High Expression of Endoplasmic Reticulum Stress-related Proteins Glucose-regulating Protein 78 and X-box Binding Protein 1 induced by Fusobacterium Nucleatum in Esophageal Squamous Cell Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo analyze the induction effect of Fusobacterium nucleatum （Fn） on endoplasmic reticulum stress-related proteins Glucose-regulating protein 78（GRP78） and X-box binding protein 1（XBP1） in esophageal squamous cell carcinoma （ESCC）， and to explore its potential mechanism and clinical significance. MethodsESCC cells KYSE150 and KYSE140 were infected with Fn for 12 h， 24 h and 48 h. The oxidative stress indexes （ROS， MDA and SOD） and the expression of GRP78 and XBP1 in each group were detected by oxidative stress index kit and Western blot. The experiment was divided into Fn groups， Fn+siNC1 groups， Fn+siGRP78 groups， Fn+siNC2 groups and Fn+siXBP1 groups； the oxidative stress indexes， paclitaxel （PTX） response efficacy， abilities of proliferation， invasion and metastasis in each group were compared. The infection of Fn and the expression of GRP78 and XBP1 in 234 ESCC and paracancerous tissues were detected by RNA scope and immunohistochemistry. The correlation between each factor and clinicopathological characteristics of patients was analyzed by Chi-square test. The influence of each factor on the survival of patients was compared by Kaplan-meier survival estimate. ResultsCompared with Fn uninfected KYSE150 and KYSE140 cells， the content of ROS and MDA was gradually increased， the activity of SOD was gradually decreased， and the expression of GRP78 and XBP1 was gradually increased in Fn infected groups （12 h， 24 h and 48 h） （P < 0.05）. Compared with Fn groups， Fn+siNC1 groups， and Fn+siNC2 groups， ROS and MDA contents were decreased， SOD activity was increased， PTX response efficacy was enhanced， and abilities of proliferation， invasion and metastasis were decreased in Fn+siGRP78 and Fn+siXBP1 groups （P < 0.05）. The rates of Fn， GRP78 and XBP1 in ESCC tissues were 43.16%， 69.66% and 60.68%， respectively. And the three indexes were significantly consistent （P < 0.05）. The patients with positive Fn infection and high expression of GRP78 and XBP1 were mostly males with a history of smoking and drinking， and the tumor differentiation degree was low， the invasion degree was deep， the lymph node metastasis rate was high， and the clinical stage was mostly stage Ⅲ/Ⅳ. The 5-year survival time of patients with above positive indexes was shortened （P < 0.05）. ConclusionsFn could induce endoplasmic reticulum stress by inducing the high expression of GRP78 and XBP1， and promote the malignant evolution of ESCC.

Biological Functions of the DNA Glycosylase NEIL3 and Its Role in Disease Progression Including Cancer.

The accumulation of oxidative DNA base damage can severely disrupt the integrity of the genome and is strongly associated with the development of cancer. DNA glycosylase is the critical enzyme that initiates the base excision repair (BER) pathway, recognizing and excising damaged bases. The Nei endonuclease VIII-like 3 (NEIL3) is an emerging DNA glycosylase essential in maintaining genome stability. With an in-depth study of the structure and function of NEIL3, we found that it has properties related to the process of base damage repair. For example, it not only prefers the base damage of single-stranded DNA (ssDNA), G-quadruplex and DNA interstrand crosslinks (ICLs), but also participates in the maintenance of replication fork stability and telomere integrity. In addition, NEIL3 is strongly associated with the progression of cancers and cardiovascular and neurological diseases, is incredibly significantly overexpressed in cancers, and may become an independent prognostic marker for cancer patients. Interestingly, circNEIL3, a circular RNA of exon-encoded origin by NEIL3, also promotes the development of multiple cancers. In this review, we have summarized the structure and the characteristics of NEIL3 to repair base damage. We have focused on NEIL3 and circNEIL3 in cancer development, progression and prognosis.

Clinical characteristics of definite vestibular migraine diagnosed according to criteria jointly formulated by the Bárány Society and the International Headache Society

Abstract Objective: To investigate the clinical features of patients with definite vestibular migraine (dVM). Methods: A total of 91 patients with vestibular symptoms accompanied by migraines/migrainelike symptoms were enrolled and diagnosed according to the criteria of the Bárány Society and the International Headache Society. Baseline data were collected. Videonystagmography and immune-related laboratory tests were performed. Results: Among the 91 patients, 62 (68.1%) had dVM (11 men, 51 women). Among dVM patients, migraine occurred earlier than vestibular symptoms in 42 (67.7%) patients. Spontaneous vertigo occurred in 41 (66.1%) patients. Induced vertigo occurred in 21 (33.9%) patients. Motion sickness occurred in 33 (53.2%) patients. Central oculomotor dysfunction was observed in 11 (17.7%) patients. Caloric test revealed unilateral horizontal semicircular canal dysfunction in 12 (19.4%) patients. Severe intolerance during the test occurred in 44 (71.0%) patients with dVM. 12 (19.4%) patients showed abnormal immune-related indicators. Conclusion: dVM is more common in women. The onset of migraine precedes that of vestibular symptoms, which are often accompanied by photophobia and phonophobia. Motion sickness and severe caloric test intolerance can contribute to the diagnosis of dVM. Immunological indicators are abnormal in some patients with dVM, dVM may be secondary or an accompanying disorder, but the causal relationship needs further investigation. Level of evidence: IV.

Monocyte to High-Density lipoprotein and Apolipoprotein A1 Ratios: Novel Indicators for Metabolic Syndrome in Chinese Newly Diagnosed Type 2 Diabetes.

Objective: Increasing evidence highlighted that chronic inflammation involved in the development of metabolic syndrome (MetS) and Type 2 diabetes mellitus (T2DM). This prospective study was aimed to assess the association between MetS and novel pro-inflammatory indicators like monocyte-to-high-density lipoprotein and monocyte-to-apolipoprotein A1 ratios (MHR and MAR) in Chinese newly diagnosed T2DM. Method: A total of 605 Chinese newly diagnosed T2DM with complete and available data were enrolled in this study. Demographic and anthropometric information were collected. Laboratory assessments were determined by standard methods. MetS was based on the Chinese Diabetes Society definition. Multiple binomial logistic regression model was used to estimate the independent variables of MHR and MAR for MetS. Receiver operating characteristic (ROC) curve was conducted to assess the optimal cutoff value of MHR and MAR in identifying MetS. Results: Overall, the prevalence of MetS was 60.2%. The correlation analysis showed that MHR and MAR were closely correlated with metabolic risk factors like body mass index, waist circumference, triglycerides, high-density lipoprotein cholesterol, systolic blood pressure, diastolic blood pressure, uric acid, and insulin resistance. MHR and MAR were also significantly associated with higher odds of MetS after adjustment for other confounders, the odds ratios (ORs) (95%CI) were 1.50 (1.14-1.97) and 2.26(1.79-2.87) respectively. Furthermore, MHR and MAR were also seemed to have higher area under the curve (AUC) for MetS than ApoA1 and monocyte alone from the ROC curve analysis (P < 0.05). The AUCs of MHR and MAR identifying MetS were 0.804 (95% CI: 0.768-0.839) and 0.840 (95% CI: 0.806-0.873) respectively (P < 0.001). The optimal cutoff values of MHR and MAR were 3.57 × 108/mmol (sensitivity: 76.1%, specificity: 73.4%) and 3.95 × 108/g (sensitivity: 79.7%, specificity: 84.6%), respectively. Conclusions: MHR and MAR were significantly associated with MetS. These two novel pro-inflammatory indicators may be useful markers for MetS in Chinese newly diagnosed T2DM.

In vitro fecal fermentation characteristics of bamboo insoluble dietary fiber and its impacts on human gut microbiota.

Bamboo contains abundant hemicellulose, cellulose, and lignin, which are a high-quality insoluble dietary fiber (IDF) raw material. To investigate IDF- induced changes in the production of short-chain fatty acids (SCFAs) and the composition of human gut microbiota, IDF was extracted by alkaline hydrogen peroxide (named BIDF), complex enzymatic hydrolysis method (named OIDF) from bamboo, and commercial bamboo fiber BF90. The in vitro fecal fermentation characteristics of BIDF, OIDF, BF90 and its impacts on human gut microbiota were studied for the first time. Results showed that BIDF, OIDF, and BF90 could promote the production of total SCFAs after 24 h fermentation. Additionally, BIDF could alter the composition and microbial diversity of gut microbiota, especially increase the relative abundance of Bacteroides and decrease the ratio of Firmicutes to Bacteroidetes (F/B) value. These results revealed that the IDF from bamboo could be partially utilized by specific bacteria in human intestines and provide a reference for the study of the effects of IDF fermentation on SCFAs production and microbial composition.

Structural, Physicochemical, and Functional Properties of Wheat Bran Insoluble Dietary Fiber Modified With Probiotic Fermentation.

Insoluble dietary fiber (IDF) were isolated from wheat bran (WB) after microbial fermentation with single or mixed strain [Lactobacillus plantarum, Lactobacillus acidophilus, Bacillus subtilis or mixed lactic acid bacteria (L. plantarum and L. acidophilus with ration of 1:1)]. Structure, physicochemical, functional properties, and antioxidant activity of the wheat bran insoluble dietary fiber (W-IDF) modified by fermentation were studied. Fourier transformed infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM) analysis suggested the successful modification of W-IDF. After fermentation with L. plantarum and mixed lactic acid bacteria, the water retention capacity (WRC), oil retention capacity (ORC), and water swelling capacity (WSC) of W-IDF were improved. The sodium cholate adsorption capacity (SCAC), and cation exchange capacity (CEC) of W-IDF modified with L. acidophilus fermentation were significantly increased. Although the cholesterol adsorption capacity (CAC) of W-IDF decreased after modification with probiotic fermentation, nitrite ion adsorption capacity (NIAC), and total phenolic content (TPC) were enhanced. Additionally, W-IDF modified by fermentation with B. subtilis or mixed lactic acid bacteria exhibited superior antioxidant capacity verified by DPPH, ABTS and total reducing power assays. Results manifested that microbial fermentation is a promising methods to modify the W-IDF to provide high-quality functional IDF for food processing and human health management.

Medial Buttress Plate and Allograft Bone-Assisted Cannulated Screw Fixation for Unstable Femoral Neck Fracture with Posteromedial Comminution: A Retrospective Controlled Study.

OBJECTIVE: To investigate the outcomes of open reduction and internal fixation combined with medial buttress plate (MBP) and allograft bone-assisted cannulated screw (CS) fixation for patients with unstable femoral neck fracture with comminuted posteromedial cortex. METHODS: In a retrospective study of patients operated on for unstable femoral neck fractures with comminuted posteromedial cortex from March 2016 to August 2020, the clinical and radiographic outcomes of 48 patients treated with CS + MBP were compared with the outcomes of 54 patients treated with CS only. All patients in the CS + MBP group were fixed by three CS and MBP (one-third tubular plates or reconstructive plates) with bone allografts. The surgery-related outcomes and complications were evaluated, including operative time, blood loss, union time, femoral head necrosis, femoral neck shortening, and other complications after the operation. The Harris score was evaluated at 12 months after the operation. RESULTS: All patients were followed up for 12-40 months. The average age of patients in the CS-only group (54 cases, 22 females) and CS + MBP group (48 cases, 20 females) was 48.46 ± 7.26 and 48.73 ± 6.38 years, respectively. More intraoperative blood loss was observed in the CS + MBP group than that of patients in CS-only group (153.45 ± 64.27 vs 21.86 ± 18.19 ml, t = 4.058, P = 0.015). The average operative time for patients in the CS + MBP group (75.35 ± 27.67 min) was almost double than that of patients in the CS-only group (36.87 ± 15.39 min) (t = 2.455, P < 0.001). The Garden alignment index of patients treated by CS + MBP from type I to type IV was 79%, 19%, 2%, and 0%, respectively. On the contrary, they were 31%, 43%, 24% and 2% for those in the CS-only group, respectively. The average healing times for the CS-only and CS + MBP groups were 4.34 ± 1.46 and 3.65 ± 1.85 months (t = 1.650, P = 0.102), respectively. Femoral neck shortening was better in the CS + MBP group (1.40 ± 1.73 mm, 9/19) than that in the CS-only group (4.33 ± 3.32 mm, 24/44). Significantly higher hip function was found in the CS + MBP group (85.60 ± 4.36 vs 82.47 ± 6.33, t = 1.899, P = 0.06). There was no statistical difference between femoral head necrosis (4% vs 11%, χ2  = 1.695, P = 0.193) and nonunion (6% vs 9%, χ2  = 0.318, P = 0.719). CONCLUSION: For unstable femoral neck fractures with comminuted posteromedial cortex, additional MBP combined with bone allografts showed better reduction quality and neck length control than CS fixation only, with longer operative time and more blood loss.