The lesser of two evils: Assessing the public acceptance of AI thermal facial recognition during the COVID-19 crisis.

AI thermal facial recognition (AITFR) has been rapidly applied globally in the fight against Coronavirus disease 2019 (COVID-19). However, AITFR has also been accompanied by a controversy regarding whether the public accepts it. Therefore, it is necessary to assess the acceptance of AITFR during the COVID-19 crisis. Drawing upon the theory of acceptable risk and Siegrist's causal model of public acceptance (PA), we built a combined psychological model that included the perceived severity of COVID-19 (PSC) to describe the influencing factors and pathways of AITFR acceptance. This model was verified through a survey conducted in Xi'an City, Shaanxi Province, China, which collected 754 valid questionnaires. The results show that (1) COVID-19 provides various application scenarios for AI-related technologies. However, the respondents' trust in AITFR was found to be very low. Additionally, the public appeared concerned about the privacy disclosure issue and the accuracy of the AITFR algorithm. (2) The PSC, social trust (ST), and perceived benefit (PB) were found to directly affect AITFR acceptance. (3) The PSC was found to have a significant positive effect on perceived risk (PR). PR was found to have no significant effect on PA, which is inconsistent with the findings of previous studies. (4) The PB were found to be a stronger mediator of the indirect effect of the PSC on ST induced by AITFR acceptance.

Division of neuromuscular compartments and localization of the center of the intramuscular nerve-dense region in pelvic wall muscles based on Sihler's staining.

The innervation of the pelvic wall muscles is not very clear. This study aimed to reveal the division of neuromuscular compartments and localize the surface position and depth of the center of the intramuscular nerve-dense region (CINDR) of the pelvic wall muscles based on Sihler's staining. Twenty-four adult cadavers were used. To localize the CINDR of the pelvic wall muscles, horizontal (H) and longitudinal (L) reference lines were drawn, and Sihler's staining was used to reveal the intramuscular nerve distribution. The CINDR projection points (P and P' points) behind and in front of the body surface, the positions of the P points projected onto the H and L lines (PH and PL points), and the depth of CINDR were determined by spiral computed tomography scanning. The piriformis and obturator internus muscles can be divided into two and three neuromuscular compartments, respectively. The PH of CINDR of the piriformis muscle was located at 22.61 ± 2.66% of the H line, the PL was at 28.53 ± 6.08% of the L line, and the puncture depth of the piriformis muscle was at 24.64 ± 2.16% of the PP' line. The PH of CINDR of the obturator internus muscle was at 16.49 ± 1.20% of the H line, the PL was at 10.94 ± 1.09% of its L line, and the puncture depth was 6.26 ± 0.38 cm. These findings may guide the design of the compartmentalized transplantation of the pelvic wall muscles and improve the target localization efficiency and efficacy for injecting botulinum toxin A to treat pelvic wall muscle spasm.

Long-term simulated microgravity alters gut microbiota and metabolome in mice.

Spaceflight and microgravity has a significant impact on the immune, central nervous, bone, and muscle support and cardiovascular systems. However, limited studies are available on the adverse effects of long-term microgravity on the intestinal microbiota, metabolism, and its relationships. In this study, a ground-based simulated microgravity (SMG) mouse model was established to evaluate the impact of long-term microgravity on gut microbiota and metabolome. After 8 weeks of SMG, alterations of the intestinal microbiota and metabolites were detected using 16S rRNA sequencing and untargeted metabolomics. Compared to the control, no significant differences in α-diversity were observed at weeks 2, 4 and 8. Nevertheless, there were clear differences in community structures at different time points. The phylum Verrucomicrobia significantly declined from 2 to 8 weeks of SMG, yet the relative abundance of Actinobacteria and Deferribacteres expanded remarkably at weeks 8. SMG decreased the genus of Allobaculum and increased Bacteroides significantly throughout the period of 8 weeks. Besides, Genus Akkermansia, Gracilibacter, Prevotella, Odoribacter, Rothia, Sporosarcina, Gracilibacter, Clostridium, and Mucispirillum were identified as biomarkers for SMG group. Desulfovibrio_c21_c20, Akkermansia_muciniphila, and Ruminococcus_gnavus dropped at week 2, which tend to recover at week 4, except for Akkermansia_muciniphila. Bacteroides_uniformis and Faecalibacterium_prausnitzii declined significantly, while Ruminococcus_flavefaciens and Mucispirillum_schaedleri elevated at week 8. Furthermore, intestinal metabolome analysis showed that 129 were upregulated and 146 metabolites were downregulated in SMG. Long-term SMG most affected steroid hormone biosynthesis, tryptophan, cysteine, methionine, arginine, proline metabolism, and histidine metabolism. Correlated analysis suggested that the potential beneficial taxa Allobaculum, Akkermansia, and Faecalibacterium were negatively associated with tryptophan, histidine, arginine, and proline metabolism, but positively with steroid hormone biosynthesis. Yet Bacteroides, Lachnospiraceae_Clostridium, Rothia, Bilophila, and Coprococcus were positively correlated with arginine, proline, tryptophan, and histidine metabolism, while negatively associated with steroid hormone biosynthesis. These results suggest that Long-term SMG altered the community of intestinal microbiota, and then further disturbed intestinal metabolites and metabolic pathways, which have great potential to help understand and provide clues for revealing the mechanisms of long-term SMG involved diseases.

Localization of the nerves innervating the pelvic floor muscles: An application to pelvic pain treatment.

The aim of this study was to achieve accurate localization of the body surface position and depth of the center of the intramuscular nerve dense region (CINDR) of the pelvic floor muscles and to establish a target site for treating pelvic floor muscle spasm or weakness. Thirty-six adult cadavers were studied in the prone position. To locate the CINDR of the levator ani and coccygeus muscles, horizontal (H) and longitudinal (L) reference lines were used. Sihler's staining revealed the intramuscular nerve dense region of the pelvic floor muscles. The CINDR was labeled with barium sulfate and spiral computed tomography scanning, and three-dimensional reconstructions were obtained. The anterior and posterior CINDR projection points (P and P'), the position of point P projected on to the H and L lines (PH and PL ), and the CINDR depth were determined using the Syngo system. The PH of the CINDR of the levator ani and the coccygeus muscle were located at (24.73 ± 0.17)% and (15.93 ± 0.31)% of the H line, respectively. The PL were located at (84.30 ± 2.47)% and (6.76 ± 0.93)% of the L line. The puncture depth of the levator ani muscle was located at (5.56 ± 0.53) cm, and the depth of the coccygeus muscle at (22.08 ± 2.11)% of the PP' line. The body surface position and depth of the CINDR of the pelvic floor muscles were conducive to locating the target more efficiently and enhancing the efficacy of botulinum toxin A injection for treating pelvic floor muscle spasm and weakness with electrical stimulation or biofeedback.

A Drug-Drug Multicomponent Crystal of Metformin and Dobesilate: Crystal Structure Analysis and Hygroscopicity Property.

A drug-drug multicomponent crystal consisting of metformin (MET) and dobesilate (DBS) was prospectively connected by solvent cooling and evaporating co-crystallization using the multicomponent crystal strategy, not only to optimize the physicochemical properties of single drugs, but also to play a role in the cooperative effect of DBS with the potential vascular protective effects of MET against diabetic retinopathy (DR). The crystal structure analysis demonstrated that MET and DBS were coupled in a 3D supramolecular structure connected by hydrogen-bonding interactions with a molar ratio of 1:1. Almost all hydrogen bond donors and receptors of MET and DBS participated in the bonding, which hindered the combination of remaining potential hydrogen bond sites and water molecules, resulting in a lower hygroscopicity property than MET alone.

Development and Characterization of a Nanobody against Human T-Cell Immunoglobulin and Mucin-3.

Monoclonal antibodies and antibody-derived biologics are essential tools for cancer research and therapy. The development of monoclonal antibody treatments for successful tumor-targeted therapies took several decades. A nanobody constructed by molecular engineering of heavy-chain-only antibody, which is unique in camel or alpaca, is a burgeoning tools of diagnostic and therapeutic in clinic. In this study, we immunized a 4-year-old female alpaca with TIM-3 antigen. Then, a VHH phage was synthesized from the transcriptome of its B cells by nested PCR as an intermediate library; the library selection for Tim-3 antigen is carried out in three rounds of translation. The most reactive colonies were selected by periplasmic extract monoclonal ELISA. The nanobody was immobilized by metal affinity chromatography (IMAC) purification with the use of a Ni-NTA column, SDS-PAGE, and Western blotting. Finally, the affinity of TIM3-specific nanobody was determined by ELISA. As results, specific 15 kD bands representing nanomaterials were observed on the gel and confirmed by Western blotting. The nanobody showed obvious specific immune response to Tim-3 and had high binding affinity. We have successfully prepared a functional anti-human Tim-3 nanobody with high affinity in vitro.

Co-Crystal of Rosiglitazone With Berberine Ameliorates Hyperglycemia and Insulin Resistance Through the PI3K/AKT/TXNIP Pathway In Vivo and In Vitro.

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. This study examined the effect and elucidated the mechanism of improvement of hyperglycemia and insulin resistance by a co-crystal of rosiglitazone with berberine (RB) in high-sugar high-fat diet (HSHFD)-induced diabetic KKAy mice. Methods: Diabetic KKAy mice were randomly divided into seven groups: KKAy model control group (DM control) treated with 3% sodium carboxymethyl cellulose; RB groups, administered daily with RB 0.7 mg/kg (RB-L), 2.11 mg/kg (RB-M), or 6.33 mg/kg (RB-H); positive control groups, administered daily with rosiglitazone 1.04 mg/kg (RSG), berberine 195 mg/kg (BBR), or combination of 1.04 mg/kg RSG and 1.08 mg/kg BBR (MIX). Test compounds were administered orally for 8 weeks. Non-diabetic C57BL/6J mice were used as normal control (NC). Blood glucose, food intake, body weight, glucose-lipid metabolism, and pathological changes in the pancreas and liver were examined. We further evaluated the mechanism of action of RB in C2C12 and HepG2 cells stimulated with high glucose and palmitate. Results: RB treatment improved glucolipid metabolism and insulin resistance in diabetic KKAy mice. RB reduced blood glucose levels, white fat index, plasma triglyceride (TG), low-density lipoprotein (LDL), gastric inhibitory peptide (GIP), and insulin levels, increased the levels of plasma glucagon-like peptide-1 (GLP-1), high-density lipoprotein (HDL), and glycogen content in the liver and muscle; and improved oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and pathological changes in the pancreas and liver of KKAy mice. Moreover, RB upregulated p-PI3K and p-AKT levels and reduced TXNIP expression in KKAy mice and in HepG2 and C2C12 cells. Conclusion: These data indicate that RB ameliorates insulin resistance and metabolic disorders, and the mechanism might be through regulating the PI3K/AKT/TXNIP signaling pathway . Thus, the co-crystal drug RB may be considered as a potential antidiabetic agent for future clinical therapy.

ZD-2, a novel DPP4 inhibitor, protects islet ß-cell and improves glycemic control in high-fat-diet-induced obese mice.

AIMS: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been extensively used for the treatment of type 2 diabetes mellitus. Nevertheless, side effects like sore throat and diarrhea also occur in DPP-4 inhibitors treatment. The study aims to identify and develop novel DPP-4 inhibitors with better therapeutic profiles. MATERIALS AND METHODS: Here we synthesized a series of vildagliptin analogs, and among which, ZD-2 showed the moderate inhibition of DPP-4 activity compared with vildagliptin. High-fat-diet (HFD) mice were treated with ZD-2 (4.5 and 7.5 mg/kg) or vildagliptin (6 mg/kg) for 7 weeks following the examinations of metabolic index and pancreatic ß-cell function. Mouse pancreatic cell line MIN6 was used to evaluate ß-cell function, and intestinal enteroendocrine cell line STC-1 was used to evaluate the expression of gut hormones. KEY FINDINGS: The IC50 of ZD-2 was over 30-fold higher than vildagliptin. However, both ZD-2 and vildagliptin treatment showed comparable effects on improving glucose tolerance and reducing the steatosis of liver and fat mass in HFD mice. Moreover, ZD-2 exerted ß-cell-protective actions by preserving islet ß-cell mass and increasing the expression of functional ß-cell-related genes. Additionally, ZD-2 also stimulated the expression of gut hormones in STC-1 cells. SIGNIFICANCE: ZD-2 showed comparable anti-diabetic activities in HFD-fed mice although its lower potency on inhibition of DPP-4 compared with vildagliptin. Protection of ß-cell function might contribute to its anti-diabetic effects.

Positive Effect of α-Asaronol on the Incidence of Post-Stroke Epilepsy for Rat with Cerebral Ischemia-Reperfusion Injury.

In the present study, we confirmed that α-asaronol, which is a product of the active metabolites of alpha Asarone, did not affect n-butylphthalide efficacy when n-butylphthalide and α-asaronol were co-administered to rats with cerebral ischemia-reperfusion injury. Our research revealed that the co-administration of α-asaronol and n-butylphthalide could further improve neurological function, reduce brain infarct volume, increase the number of Nissl bodies, and decrease the ratios of apoptotic cells and the expression of the caspase-3 protein for cerebral ischemia-reperfusion injury model compared to n-butylphthalide alone. Additionally, α-asaronol could significantly decrease the incidence of post-stroke epilepsy versus n-butylphthalide. This study provides valuable data for the follow-up prodrug research of α-asaronol and n-butylphthalide.

Multicomponent Crystal of Metformin and Barbital: Design, Crystal Structure Analysis and Characterization.

The formation of most multicomponent crystals relies on the interaction of hydrogen bonds between the components, so rational crystal design based on the expected hydrogen-bonded supramolecular synthons was employed to establish supramolecular compounds with desirable properties. This theory was put into practice for metformin to participate in more therapeutic fields to search for a fast and simple approach for the screening of candidate crystal co-formers. The prediction of intermolecular synthons facilitated the successful synthesis of a new multicomponent crystal of metformin (Met) and barbital (Bar) through an anion exchange reaction and cooling crystallization method. The single crystal X-ray diffraction analysis demonstrated the hydrogen bond-based ureide/ureide and guanidine/ureide synthons were responsible for the self-assembly of the primary structural motif and extended into infinite supramolecular heterocatemeric structures.

The overall distribution pattern of the hand's cutaneous nerves and its clinical implications in sensory reconstruction / Patrón de distribución general de los nervios cutáneos de la mano y sus implicancias clínicas en la reconstrucción sensorial

SUMMARY: The objective of this study was to reveal the overall distribution pattern of the hand's cutaneous nerves to provide a morphological basis for the selection and matching of the hand skin for sensory reconstruction during flap transplantation. The hands of 12 adult cadavers were used for the study. Palmar region and dorsum of the hand were divided into regions I-VI. The skin of the hand containing subcutaneous fat was removed close to the muscle surface. The modified Sihler's staining method was used to visualize the overall distribution pattern of the cutaneous nerves and the areas they innervate. The median nerve, superficial branch of the ulnar nerve, and the superficial branch of the radial nerve innervated 59.27 % (containing 4.65 % of the palmar cutaneous branch of the median nerve), 36.91 %, and 3.82 % of the palm area, respectively. The superficial branch of the radial nerve, the dorsal branch of the ulnar nerve, and the median nerve innervated 45.16 %, 47.25 %, and 7.59 % of the hand's dorsal skin area, respectively. Communication was found between the arborized branches of these cutaneous nerves. Region III of the palm and region VI of the dorsum of the hand had relatively more dense nerve distribution. Except for region V, the density of the total nerve branches in each palm region was higher than that of the dorsum of the hand. The total number of nerve branches in the distal phalanx and dorsum decreased from the thumb to the digitus minimus. Our results provide morphological guidance when designing a reasonable matching flap to improve the hand's sensory function reconstruction.

RESUMEN: El objetivo de este estudio fue revelar el patrón de distribución general de los nervios cutáneos de la mano y proporcionar una base morfológica para la selección y adaptación de la piel de la mano, para la reconstrucción sensorial durante el trasplante de colgajo. Para el estudio se utilizaron 12 manos de cadáveres adultos. Las regiones palmar y dorsal se dividieron en regiones I-VI. La piel de la mano que contiene grasa subcutánea se eliminó cerca de la superficie del músculo. Para visualizar el patrón de distribución general de los nervios cutáneos y las áreas que inervan se utilizó el método de tinción de Sihler modificado. El nervio mediano, la rama superficial del nervio ulnar y la rama superficial del nervio radial inervaban el 59,27 % (que contenía el 4,65 % de la rama cutánea palmar del nervio mediano), el 36,91 % y el 3,82 % del área de la palma, respectivamente. La rama super-ficial del nervio radial, la rama dorsal del nervio ulnar y el nervio mediano inervaban el 45,16 %, el 47,25 % y el 7,59 % del área dorsal de la mano, respectivamente. Se observó comunicación entre las ramas arborizadas de estos nervios cutáneos. La región III de la palma y la región VI del dorso de la mano tenían una distribución nerviosa relativamente más densa. A excepción de la región V, la densidad de las ramas nerviosas totales en cada región de la palma fue mayor que el dorso de la mano. El número total de ramas nerviosas en la falange distal y el dorso disminuyó desde el pulgar hasta el dedo mínimo. Nuestros resultados proporcionan una guía morfológica al diseñar un colgajo compatible razonable para mejorar la reconstrucción de la función sensorial de la mano.

CQMUH-011 mitigates autoimmune hepatitis via inhibiting the function of T lymphocytes.

CQMUH-011 is a modified adamantane sulfonamide compound, that inhibits macrophage proliferation and possesses anti-inflammatory properties. Here, fresh mouse splenocytes were obtained and stimulated with concanavalin A (ConA, 5 µg/ml) in vitro; and experimental autoimmune hepatitis (AIH) was induced by ConA (20 mg/kg, iv) in vivo, to clarify the protective effects of CQMUH-011 against AIH and its possible mechanisms. Our results demonstrated that CQMUH-011 pretreatment can dose-dependently inhibit the proliferation of splenocytes in vitro. In vivo, CQMUH-011 administration reduced the hepatic histopathological score and the infiltration of lymphocytes in the liver parenchyma; additionally, it downregulated the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and pro-inflammatory cytokines interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in serum, as well as those of methane dicarboxylic aldehyde and myeloperoxidase in the liver tissues. It also down-regulated the expression of p-NF-κB and related proteins in the liver tissues. Furthermore, CQMUH-011 could maintain the balance of CD3+ CD4+ /CD3+ CD8+ and decrease the percentages of CD8+ CD69+ and CD4+ CD25+/- CD69+ T-cells in the splenocytes of ConA-challenged mice. Moreover, we found thatCD4+ CD25+/- CD69+ T-cells were significantly correlated with ALT levels, especially CD4+ CD25- CD69+ T-cells. In conclusion, CQMUH-011 exerts potential protective effects against ConA-induced hepatitis, which may be partially attributed to its inhibition of T cells, especially the suppression of the proliferation of CD4+ CD25- CD69+ and CD8+ CD69+ subsets in the spleen. CQMUH-011 also reduced the early apoptosis of lymphocytes in the thymus.

CQMUH-011 Inhibits LPS-Induced Microglia Activation and Ameliorates Brain Ischemic Injury in Mice.

Excessive microglial activation-mediated neuroinflammation is closely involved in the pathogenesis of several neurological diseases. CQMUH-011, as a novel adamantane sulfonamide compound, has been shown anti-inflammatory properties in activated macrophages (RAW264.7). However, the role of CQMUH-011 in microglial activation-induced neuroinflammation and neuroprotective properties has yet to be elucidated. In the present study, we investigated the potential effects and mechanisms of CQMUH-011 on lipopolysaccharide (LPS)-stimulated primary microglia in vitro and transient middle cerebral artery occlusion (t-MCAO)-induced acute cerebral ischemia/reperfusion (I/R) injury in vivo. The results demonstrated that CQMUH-011 significantly suppressed the production of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß by LPS-stimulated primary microglia. In addition, CQMUH-011 inhibited the proliferation of activated microglia by arresting the cell cycle at the G1/S phase accompanied by downregulating the expression of cell cycle regulatory proteins such as proliferating cell nuclear antigen (PCNA) and cyclin D1. CQMUH-011 was seen to induce apoptosis in activated microglia by regulating the expression of Bax and Bcl-2. Furthermore, CQMUH-011 markedly attenuated the protein expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88) as well as the phosphorylation levels of nuclear factor-kappa (NF-κB) subunit p65, inhibitory kappa B-alpha (IκBα), and mitogen-activated protein kinases (MAPKs) such as extracellular signal-regulated kinase (ERK) and p38 kinases. In vivo, CQMUH-011 administration significantly improved neurological function and infarct volume, and ameliorated the inflammatory cytokines and microglia amount around the injury site of mice. In conclusion, these results suggested that CQMUH-011 has a notable anti-inflammatory effect and protects mice from I/R injure. Thus, CQMUH-011 may be a candidate drug for the treatment of cerebral ischemia patients.

Risk Information Seeking Behavior in Disaster Resettlement: A Case Study of Ankang City, China.

In 2011, the Chinese government launched a disaster mitigation and preparedness program called the Resettlement of South Shaanxi (RSS). Due to the wide geographical scope and complex interests, the possibility of conflicts was increased during and after resettlement. Efficient risk communication improves the supply of information about risks and meets the risk-related information needs of individuals. Using the risk information seeking and processing (RISP) model, this research applied a structural equation model and survey with a structured questionnaire to study ways to improve risk communication in disaster resettlement. A total of 616 valid questionnaires were provided by study respondents in resettlement sites in Ziyang County, Ankang City, Shaanxi Province. The results indicated the following: (1) the public's information seeking behavior relies more on village committees and village officials than other channels. Emerging information channels, such as Weibo and WeChat (social media applications in China), do not play leading roles in disseminating risk information. (2) There are differences between the information channels used by residents and the channels that residents believe the most. (3) Relevant channel beliefs, information sufficiency, perceived hazard characteristics, and self-efficacy directly influence risk information seeking behavior. However, the capacity to gather information has non-significant direct influences on information seeking behavior. (4) Perceived hazard characteristics and self-efficacy drive risk information seeking behavior in both direct and indirect ways through information sufficiency.

A New Co-Crystal of Synthetic Drug Rosiglitazone with Natural Medicine Berberine: Preparation, Crystal Structures, and Dissolution.

A co-crystal of rosiglitazone (Rsg) with berberine (Bbr), Rsg-Bbr, was prepared by the solvent evaporation method and characterized. The results showed that the electrostatic attraction existed between the nitrogen anion of rosiglitazone and the quaternary ammonium cation of berberine, and C-H···O hydrogen bonds were formed between Rsg and Bbr. In the crystal structure, rosiglitazone molecules stack into a supramolecular layer through π-π interactions while π-π interactions between berberine cations also result in a similar layer. The co-crystal presented a low moisture adsorption curve in the range of 0-95% relative humidity values at 25 °C. The improved dissolution rate of rosiglitazone in pH = 6.8 buffer solution could be achieved after forming co-crystal.

Recommendation of the best site based on the distribution pattern of extramuscular and intramusular nerves for gluteal muscle injection / Recomendación del mejor sitio para la inyección del músculo glúteo basado en el patrón de distribución de los nervios extramusculares e intramusculares

To reveal the extra- and intramuscular nerve distribution patterns of the gluteus maximus, medius, and minimus, and to provide guidance for gluteal muscle injection in order to avoid nerve injury. Ten adult and 10 child cadavers were used. The superior and inferior gluteal nerves innervating the gluteus maximus, medius, and minimus were dissected, exposed, and sutured in-situ on the muscle. The three gluteal muscles were removed, and the distribution patterns of the intramuscular nerves were revealed by modified Sihler's nerve staining. The nerve distribution pattern was returned to the corresponding position in the body, and the patterns in the four quadrants of the buttock were analyzed. There were 3-12 extramuscular nerve branches of the gluteus maximus, medius, and minimus. After entering the muscle, these nerve branches arborized and anastomosed to form an arc-shaped, nerve-dense zone. The nerve distribution was most dense in the inferomedial region of the superolateral quadrant and the inferolateral region of the superomedial quadrant of the buttocks. The nerve distribution was relatively dense in the inferolateral region of the superolateral quadrant, and the medial region of the inferomedial quadrant. An arc-shaped, nerve-sparse zone in the superolateral and superomedial quadrants near the lower iliac crest accounted for about two-fifths of the two quadrants' limits. The arc-shaped, nerve-sparse zone in the superolateral quadrant is the preferred injection site, and the superomedial quadrant near the lower iliac crest is also recommended as a gluteal intramuscular injection region, free from nerve injury.

El objetivo de este trabajo fue revelar los patrones de distribución nerviosa extramusculat e intramuscular de los músculos glúteo máximo, medio y mínimo y proporcionar orientación para la inyección en la región glútea con el propósito de evitar lesiones nerviosas. Se utilizaron diez cadáveres adultos y diez niños. Los nervios glúteos superior e inferior que inervan a los músculos glúteo máximo, medio y mínimo fueron disecados, expuestos y suturados in situ en el músculo. Se extirparon los tres músculos glúteos y se revelaron los patrones de distribución de los nervios intramusculares mediante la tinción nerviosa de Sihler modificada. El patrón de distribución nerviosa se devolvió a la posición correspondiente en el cuerpo y se analizaron los patrones en los cuatro cuadrantes de la región glútea. Se encontraron 3 a 12 ramos nerviosos extramusculares de los músculos glúteo máximo, medio y mínimo. Después de ingresar al músculo, estas ramas nerviosas se arborizaron y anastomizaron para formar una zona densamente nerviosa en forma de arco. La distribución nerviosa fue de mayor densidad en la región inferomedial del cuadrante superolateral y en la región inferolateral del cuadrante superomedial de la región glútea. La distribución nerviosa era relativamente densa en la región inferolateral del cuadrante superolateral y en la región medial del cuadrante inferomedial. Una zona en forma de arco en los cuadrantes superolateral y superomedial y con escasa inervación, cerca de la cresta ilíaca representaba una parte de los límites de los dos cuadrantes. La zona de poca inervación en forma de arco en el cuadrante superolateral es el sitio de inyección preferido, y el cuadrante superomedial próximo a la cresta ilíaca también se recomienda como una región de inyección intramuscular glútea, libre de lesión nerviosa.

VHL mutation-mediated SALL4 overexpression promotes tumorigenesis and vascularization of clear cell renal cell carcinoma via Akt/GSK-3ß signaling.

BACKGROUND: Although ongoing development of therapeutic strategies contributes to the improvements in clinical management, clear cell renal cell carcinoma (ccRCC) deaths originate mainly from radiochemoresistant and metastatic disease. Transcription factor SALL4 has been implicated in tumorigenesis and metastasis of multiple cancers. However, it is not known whether SALL4 is involved in the pathogenesis of ccRCC. METHODS: Analyses of clinical specimen and publicly available datasets were performed to determine the expression level and clinical significance of SALL4 in ccRCC. The influence of SALL4 expression on ccRCC tumor growth, metastasis and vascularity was evaluated through a series of in vitro and in vivo experiments. Western blotting, immunofluorescence staining and integrative database analysis were carried out to investigate the underlying mechanism for SALL4-mediated oncogenic activities in ccRCC. RESULTS: SALL4 expression was increased in ccRCC and positively correlated with tumor progression and poor prognosis. SALL4 could promote ccRCC cell proliferation, colony formation, cell cycle progression, migration, invasion and tumorigenicity and inhibit cell senescence. Further investigation revealed a widespread association of SALL4 with individual gene transcription and the involvement of SALL4 in endothelium development and vasculogenesis. In the context of ccRCC, SALL4 promoted tumor vascularization by recruiting endothelial cells. In addition, we found that SALL4 could exert its tumor-promoting effect via modulating Akt/GSK-3ß axis and VEGFA expression. VHL mutation and DNA hypomethylation may be involved in the upregulation of SALL4 in ccRCC. CONCLUSIONS: Overall, our results provide evidence that upregulated SALL4 can function as a crucial regulator of tumor pathogenesis and progression in ccRCC, thus offering potential therapeutic strategies for future treatment.

The Anti-Breast Cancer Effect and Mechanism of Glimepiride-Metformin Adduct.

BACKGROUND: Compound adduct is a eutectic crystal formed by non-covalent bonds of two compounds or multiple compounds with water. Emerging evidence suggests that adduct could be different from the simple physical mixture of the individual compounds and has some new features. Recent studies reported that both glimepiride (Gli) and metformin (Met) may possess an anti-breast cancer effect besides anti-diabetic effect. In the current study, we synthesized glimepiride-metformin adduct (GMA) and examined its anti-breast cancer effect in vitro and in vivo to explore its potential in treatment of breast cancer in diabetic patients. METHODS: GMA was synthesized from Gli, Met and water at a molar molecular mass of 1:1:1 and identified by infrared spectroscopy. MTT assay, colony formation assay and wound healing assay were performed to examine the effects of GMA on cell viability and migration of human breast cancer cell lines CAL-148, MDA-MB-453, MDA-MB-231and MCF-7. The effect of GMA on cell cycle and apoptosis was examined by flow cytometry. The orthotopic implantation model was established to observe the inhibitory effect of GMA on tumor growth. The expression of Ki67 was detected by immunohistochemistry. RT-qPCR and Western blotting were performed to investigate mechanisms for the function of GMA. RESULTS: Both MTT and colony formation assays showed that GMA inhibited breast cancer cell viability, and the effect was greater than Gli alone, Met alone and the combination. In vivo study showed that GMA had an inhibitory effect on tumor growth of CAL-148 xenografts. Flow cytometry analysis indicated that GMA induced G1/S phase cell cycle arrest and apoptosis in breast cancer cells. RT-qPCR and Western blotting analyses showed that GMA activated AMPK, and up-regulated expression of p53 and p21, and down-regulated expression of cyclin D1 and CDK4. CONCLUSION: GMA suppresses cell viability of breast cancer cells, and its effect is greater than Gli and Met alone or combination at the same concentration. GMA inhibits breast cancer cell growth in vivo. The antitumor effect of GMA may be related to the activation of AMPK resulting in up-regulation of p53 and p21 and down-regulation of cyclin D1 and CDK4.

Spalt-Like Protein 4 (SALL4) Promotes Angiogenesis by Activating Vascular Endothelial Growth Factor A (VEGFA) Signaling.

BACKGROUND Spalt-like protein 4 (SALL4) is a nuclear transcription factor central to early embryonic development, especially for regulating pluripotency of embryonic stem cells (ESCs) and sustaining ESCs self-renewal. Aberrant re-expression of SALL4 in adult tissues is involved in tumorigenesis and cancer progression. However, the role of SALL4 in angiogenesis remains elusive. Here, we determined the potential action of SALL4 on proliferation, migration, and tube formation of endothelial cells. MATERIAL AND METHODS HUVECs were infected with lentiviral particles expressing shRNA against SALL4. QRT-PCR and immunoblotting analysis were carried out to evaluate knockdown efficiency at mRNA and protein levels. Cell proliferation was measured by CCK-8 assay and flow cytometry was conducted to analyze cell cycle distribution. Wound-healing and Transwell migration assays were performed to evaluate cell motility. In addition, we determined the role of SALL4 on angiogenesis by tube formation assay, and Western blot analysis was used to assess the effect of SALL4 downregulation on VEGFA expression. RESULTS We found that SALL4 downregulation resulted in decreased proliferation. Cell cycle analysis revealed that SALL4 knockdown impeded cell cycle progression and induced cell cycle arrest at G1 phase. We also found that silencing of SALL4 decreased the capacity of wound healing and cell migration in HUVECs. Furthermore, tube formation assay showed that loss of SALL4 inhibited HUVECs angiogenesis. We also observed that SALL4 knockdown reduced the level of VEGFA in HUVECs. CONCLUSIONS In conclusion, these results support that by promoting proliferation, cell cycle progression, migration, and tube formation, SALL4 is involved in the process of angiogenesis through modulating VEGFA expression.

Improving Dissolution and Cytotoxicity by Forming Multidrug Crystals.

Both rosiglitazone and metformin have effects on blood glucose regulation and the proliferation of liver cancer cells. Combination therapy with these two drugs is common and effective for the treatment of diabetes in the clinic, however, the application of these two drugs is influenced by the poor dissolution of rosiglitazone and the gastrointestinal side-effect of metformin resulting from a high solubility. The formation of a multidrug crystal form (Rsg-Met) by a solvent evaporation method can solve the solubility issue. Crystal structure data and intramolecular hydrogen bonds were detected by X-ray diffraction and infrared spectroscopy. Surprisingly, Rsg-Met shortens the time spent in solubility equilibrium and multiplies the dissolution rate of Rsg. Finally, we found that a low concentration of Rsg-Met enhanced the proliferation inhibition effect on liver cancer cells (HepG2, SK-hep1) compared with rosiglitazone, without affecting the human normal cell line LO2.