Morphologic variations of the superior intercostal vein: An anatomical study with clinical applications.

This study aimed to validate and compare the anatomical variations of the superior intercostal veins, focusing on their origin, course, anastomoses, and destination. In addition, the results were compared with findings from other relevant studies. Fifty Korean and 16 Chinese adult cadavers were dissected for this study. The superior intercostal veins were dissected and measured. In our study of 66 specimens, the right superior intercostal vein was observed in 92.3% of cases, while the left superior intercostal vein was observed in 50%. The right superior intercostal vein was subdivided into six types based on its composition, which mainly drained the second and third right posterior intercostal veins. Similarly, the left superior intercostal vein was subdivided into eight types, primarily involving the second to fourth left posterior intercostal veins. This detailed anatomical study successfully identified and classified the various morphologic types of the superior intercostal vein and reviewed the clinical significance of this vein. The findings of this study can offer valuable anatomical evidence to physicians, aiding in their understanding and utilization of the superior intercostal vein.

Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis.

Chiral ketones and their derivatives are useful synthetic intermediates for the synthesis of biologically active natural products and medicinally relevant molecules. Nevertheless, general and broadly applicable methods for enantioenriched acyclic α,α-disubstituted ketones, especially α,α-diarylketones, remain largely underdeveloped, owing to the easy racemization. Here, we report a visible light photoactivation and phosphoric acid-catalyzed alkyne-carbonyl metathesis/transfer hydrogenation one-pot reaction using arylalkyne, benzoquinone, and Hantzsch ester for the expeditious synthesis of α,α-diarylketones with excellent yields and enantioselectivities. In the reaction, three chemical bonds, including C═O, C─C, and C─H, are formed, providing a de novo synthesis reaction for chiral α,α-diarylketones. Moreover, this protocol provides a convenient and practical method to synthesize or modify complex bioactive molecules, including efficient routes to florylpicoxamid and BRL-15572 analogs. Computational mechanistic studies revealed that C-H/π interactions, π-π interaction, and the substituents of Hantzsch ester all play crucial roles in the stereocontrol of the reaction.

TOPK Affects Autophagy of Skin Squamous Cell Carcinoma by Regulating NF-KB Pathway through HDAC1.

Objective: To explore the effect and potential mechanism of T-LAK cell-originated protein kinase (TOPK) on autophagy in cutaneous squamous cell carcinoma (cSCC). Methods: Human cSCC cancer tissue and paracancerous tissue samples were collected clinically; immunohistochemistry was used to detect the expression of TOPK, nuclear factor κB p65 (NF-κB p65), phosphorylated nuclear factor κB inhibitor α (p-IκBα), Beclin-1, and microtubule-associated protein 1 light chain 3 (LC3) in cSCC tissue; and immunofluorescence was adopted to detect the coexpression of NF-κB p65, p-IκBα, and TOPK in cSCC tissue. After TOPK silencing or overexpression, SCL-1 and A431 cells were treated with PDTC and 3-MA, respectively. RT-qPCR and Western Blot were used to detect the mRNA and protein expressions of histone deacetylase 1 (HDAC1) in TOPK-silenced/overexpressing cells. Western Blot was performed to detect the protein expressions of NF-κB p65, p-p65, IκBα, p-IκBα, Beclin-1, and LC3 in each group. Transwell and scratch healing experiments were used to detect the ability of cells to invade and migrate. The formation of autophagosomes in each group was observed by TEM. Results: Compared with adjacent tissues, TOPK, NF-κB p65, p-IκBα, Beclin-1, and LC3 were highly expressed in cSCC cancer tissues; TOPK and NF-κB p65 were coexpressed; and TOPK and p-IκBα were expressed in cSCC cancer tissues both increased. The mRNA and protein levels of TOPK in human cSCC cells were significantly higher than those in human normal skin HaCaT cells. After TOPK knockout, the expression of HDAC1, p-IκBα/IκBα, NF-κB p65, p-p65, Beclin-1, LC3II/I proteins, cell invasion, and migration abilities were significantly reduced, and fewer autophagosomes were observed. Treatment with PDTC and 3-MA significantly downregulated NF-κB pathway protein activity and autophagy level and reduced cell migration and invasion ability. Conclusion: TOPK promotes the malignant progression of cSCC by upregulating HDAC1 to activate the NF-κB pathway and promote autophagy.

Dipeptidyl peptidase-8 induces sorafenib resistance via binding with c-Rel to mediate NF-κB signaling in hepatocellular carcinoma.

Sorafenib is the important first-standard drug for patients with advanced hepatocellular carcinoma (HCC). A major obstacle to successful treatment is sorafenib resistance. However, the mechanism of sorafenib resistance is unclear. The present study aimed to determine the involvement of dipeptidyl peptidase-8 (DPP8) in sorafenib resistance. DPP8 expression was detected using quantitative real-time PCR (qPCR) and western blot analysis. The effect of DPP8 on sorafenib resistance was examined using terminal deoxynulceotidyl transferase nick-end-labeling (TUNEL), colony formation, flow cytometry, luciferase reporter, immunofluorescence, and immunoprecipitation (IP) assays. We found that DPP8 mRNA and protein levels were dramatically upregulated in HCC. Gene set enrichment analysis (GSEA) illustrated that DPP8 might be involved in apoptosis regulation. Downregulation of DPP8 substantially promoted the sensitivity of HCC cells to sorafenib. Further analysis showed that DPP8 might regulate nuclear factor kappa B (NF-κB) signaling, which was confirmed using a luciferase reporter assay. Downregulation of DPP8 decreased the expression levels of downstream genes of the NF-κB pathway. IP showed that DPP8 can interact with NF-κB subunit c-Rel, an important protein of NF-κB signaling. Finally, a drug combination of sorafenib and Val-boroPro induced higher mortality of HCC cells than sorafenib alone in DPP8-upregulated cells. Our findings indicated that using the inhibitor Val-boroPro might be a promising method to enhance sorafenib sensitivity in advanced HCC.

Dearomatization of 2,3-Disubstituted Indoles via 1,8-Addition of Propargylic (Aza)-para-Quinone Methides.

Dearomatization of indole is a useful strategy to access indolimines: a motif widely exists in biologically active molecules and natural products. Herein, an efficient method for the dearomatization of 2,3-disubstituted indoles to generate diverse indolimines with tetrasubstituted allenes is described. This work accomplishes dearomatization of 2,3-disubstituted indoles through 1,8-addition of (aza)-para-quinone methides, which are generated in situ from propargylic alcohols. A series of synthetically useful indolimines containing quaternary carbon centers and tetrasubstituted allenes can be accessed in good yields (up to 99%). Additionally, the separability of product isomers, diversified product transformations, and easy scale-up of the reaction demonstrate the potential application of this method.

Formal (3 + 4)-Annulation of Propargylic p-Quinone Methides with 2-Indolylmethanols: Synthesis of Polysubstituted Indole-Fused Oxepines.

A novel Brønsted acid catalyzed 1,8-addition mediated (3 + 4)-annulation of in situ generated propargylic p-quinone methides with 2-indolylmethanols is described. This method provides a convenient and mild approach to structurally interesting and synthetically important polysubstituted indole-fused oxepines in high yields. Moreover, 2-indolylmethanols as four-atom synthons in the (3 + 4)-annulations under Brønsted acid conditions have been explored for the first time.

Expression and prognostic significance of thrombospondin gene family in gastric cancer.

BACKGROUND: Thrombospondins (THBSs) are glycoproteins expressed in the extracellular matrix (ECM) and have critical roles in tumor development and metastasis. However, the diverse expression patterns and prognostic roles of distinct THBS genes in gastric cancer have not been fully elucidated. In the current study, we aimed to investigate the expression patterns of THBSs in gastric cancer (GC) and determine whether they are prognostic markers for this malignancy. METHODS: mRNA expression status and genetic mutations of THBS family members were performed by using ONCOMINE, UCSC Xena browser, GEPIA, and cBioPortal databases. Prognostic values and function enrichment analysis of the members were assessed via Kaplan-Meier plotter and Metascape. RESULTS: we found that the mRNA expression of THBS1, THBS2, THBS4, and COMP were higher in patients with GC tissues than those in normal gastric mucosa and there was no difference in the mRNA expression of THBS3 between GC and normal tissue. Survival analysis revealed that mRNA levels of THBSs were strongly related to worse OS in GC patients (P<0.05). Overexpression of THBSs indicated poor OS in stage III/IV GC and high expression of THBS1, THBS3, THBS4, and COMP were related to worse OS in stage II GC. CONCLUSIONS: Bioinformatics analysis revealed a better understanding the value of THBS family members in GC and suggest that THBSs might serve as potential prognostic biomarkers for GC.

N-(4-(2-chloro-4-(trifluoromethyl)phenoxy)phenyl)picolinamide as a new inhibitor of mitochondrial complex III: Synthesis, biological evaluation and computational simulations.

Mitochondrial complex III is one of the most promising targets for a number of pharmaceuticals and fungicides. Due to the wide-spreaduse of complex III-inhibiting fungicides, a considerable increase of resistance has occurred worldwide. Therefore, inhibitors with novel scaffolds and potent activity against complex III are still in great demand. In this article, a new series of amide compounds bearing the diaryl ether scaffold were designed and prepared, followed by the biological evaluation. Gratifyingly, several compounds demonstrated potent activity against succinate-cytochrome c reductase (SCR, a mixture of mitochondrial complex II and complex III), with compound 3w possessing the best inhibitory activity (IC50 = 0.91 ± 0.09 µmol/L). Additional studies verified that 3w was a new inhibitor of complex III. Moreover, computational simulations elucidated that 3w should bind to the Qo site of complex III. We believe this work will be valuable for the preparation and discovery of more complex III inhibitors.

Analysis on Three-Dimensional Strength Influencing Factors and Control Measures of Asphalt Mixtures.

Strength is an important parameter for the design of asphalt pavement materials and structures. To study the influence of various factors on the three-dimensional strength of asphalt mixtures, three aggregate gradations (dense-graded bituminous mixture AC-13, stone mastic asphalt SMA-13 and bituminous stabilization aggregate paving mixture OGFC-13) and two binders (SBS modified bitumen and 70# base bitumen) were used to prepare the asphalt mixture specimens. Among them, SBS+SMA-13 asphalt mixture has the best performance. On this basis, the uniaxial compressive test, uniaxial tensile test and confining triaxial test were conducted on the SBS+SMA-13 asphalt mixture under six oil-stone ratios conditions (5.5%, 5.7%, 5.9%, 6.1%, 6.3%, and 6.5%), six temperatures conditions (5 °C, 10 °C, 15 °C, 20 °C, 25 °C, and 30 °C), and five loading rates conditions (1 mm/min, 2 mm/min, 3 mm/min, 4 mm/min, and 5 mm/min). In addition, a unified three-dimensional strength calculation model considering the influence of temperature, loading rate, and oil-stone ratio was proposed, and the change law of the three-dimensional strength with these above factors was revealed. Furthermore, two sets of three-factor three-level orthogonal tests were carried out on the SMA-13 asphalt mixture. The sensitivity analysis and strength regulation research between three-dimensional strength and each factor were carried out. The results show that the type of asphalt has the greatest influence on the strength of the mixture, the temperature has the second most influence, the loading rate has less influence, and the oil-stone ratio has the least influence. The strength regulations proposed to improve the strength of the asphalt mixture include the use of modified asphalt, high-temperature stability high-quality asphalt, and the lower oil-stone ratio than the Marshall optimal oil-stone ratio. The strength control measures proposed from the perspective of the three-dimensional stress state, the joint failure of each stress components and real stress states are taken into consideration.

N-(3,5-Dichloro-4-(2,4,6-trichlorophenoxy)phenyl)benzenesulfonamide: A new dual-target inhibitor of mitochondrial complex II and complex III via structural simplification.

Mitochondrial complex II and complex III are two promising targets for the development of numerous pharmaceuticals and pesticides. Although tremendous inhibitors of either complex II or complex III were identified, compounds which are capable of prohibiting the activities of both complexes have been rarely reported. Since multi-target drugs can interact with several drug targets simultaneously, we were keen on discovering new and potent dual-target inhibitors of both complex II and complex III. Therefore, a new series of structurally simplified sulfonamides bearing a diaryl ether scaffold were designed and synthesized in this paper. Afterwards, the biological activities of the newly synthesized compounds were evaluated. The results implied that several compounds demonstrated outstanding potency against succinate-cytochrome c reductase (SCR, a mixture of complex II and complex III). Further studies confirmed that N-(3,5-Dichloro-4-(2,4,6-trichlorophenoxy)phenyl)benzenesulfonamide (3f), a representative compound herein, was identified as a dual-target inhibitor of both complexes. Furthermore, computational simulations were also performed to have a better understanding about binding of 3f to the enzyme complexes, which concluded that 3f should bind to complex II and the Qo site of complex III. Consequently, we harbor the idea that this work can be beneficial for the synthesis and discovery of more dual- or multi-target inhibitors.

In†situ Generated Ruthenium Catalyst Systems Bearing Diverse N-Heterocyclic Carbene Precursors for Atom-Economic Amide Synthesis from Alcohols and Amines.

The transition-metal-catalyzed direct synthesis of amides from alcohols and amines is herein demonstrated as a highly environmentally benign and atom-economic process. Among various catalyst systems, in situ generated N-heterocyclic carbene (NHC)-based ruthenium (Ru) halide catalyst systems have been proven to be active for this transformation. However, these existing catalyst systems usually require an additional ligand to achieve satisfactory results. In this work, through extensive screening of a diverse variety of NHC precursors, we discovered an active in situ catalyst system for efficient amide synthesis without any additional ligand. Notably, this catalyst system was found to be insensitive to the electronic effects of the substrates, and various electron-deficient substrates, which were not highly reactive with our previous catalyst systems, could be employed to afford the corresponding amides efficiently. Furthermore, mechanistic investigations were performed to provide a rationale for the high activity of the optimized catalyst system. NMR-scale reactions indicated that the rapid formation of a Ru hydride intermediate (signal at δ=-7.8 ppm in the 1 H NMR spectrum) after the addition of the alcohol substrate should be pivotal in establishing the high catalyst activity. Besides, HRMS analysis provided possible structures of the in situ generated catalyst system.

Intermuscular aponeuroses between the flexor muscles of the forearm and their relationships with the ulnar nerve.

INTRODUCTION: The aim of this study was to clarify the morphological characteristics of the intermuscular aponeurosis between the flexor carpi ulnaris (FCU) and flexor digitorum superficialis (FDS; IMAS), and that between the FCU and flexor digitorum profundus (FDP; IMAP), and their topographic relationships with the ulnar nerve. MATERIALS AND METHODS: Fifty limbs of 38 adult cadavers were studied. RESULTS: The IMAS extended along the deep surface of the FCU adjoining the FDS, having the appearance of a ladder, giving off "steps" that decreased in width from superficial to deep around the middle of the forearm. Its proximal part divided into two bands connected by a thin membrane, and was attached to the medial epicondyle and the tubercle (the most medial prominent part of the coronoid process of the ulna), respectively. The IMAP extended deep between the FCU and FDP from the antebrachial fascia, and its distal end was located on the posterior border of the FCU. The IMAP became broader toward its proximal part, and its proximal end was attached anterior and posterior to the tubercle and the olecranon, respectively. The ulnar nerve passed posterior to the medial epicondyle and then medial to the tubercle, and was crossed by the deep border of the IMAS at 58.3 ± 14.1 mm below the medial epicondyle. CONCLUSION: The deep border of the IMAS and aberrant tendinous structure passing across the ulnar nerve, or the parts of the IMAS and IMAP passing posterior to the ulnar nerve are potential causes of ulnar nerve compression.

Zuckerkandl's tubercle of the thyroid gland: Its location in the anatomical position, and comparative morphology of the same specimens before and after fixation.

The aim of this study was to elucidate the definition of the borders and surface of the thyroid lobe in the anatomical position, and to compare the morphology of Zuckerkandl's tubercle (ZT) in the fresh and fixed states. One hundred thyroid lobes from 50 fresh Korean cadavers were used. The lateral border of the thyroid lobe could be defined as the most lateral margin of its anterior aspect when in the anatomical position. The posteromedial border was the margin that projected toward the trachea or tracheoesophageal groove. The lateral and posteromedial borders, and the posterior surface between these borders, could be identified in most of the fixed cadavers. The posterolateral border could only be identified in the thyroid lobe if there was compression by the internal carotid artery in cross-sectioned specimens and CT images. The ZT was identifiable in 85% of both fresh and fixed specimens. It was identified mainly at the posteromedial border of the thyroid lobe when in the anatomical position, and extended to the tracheoesophageal groove or esophagus. In the fresh state, the ZT projected as a rounded cone with a usually semicircular base, but its shape was very variable in the fixed state. In the present study, the ZT was found at the posteromedial border or posterior surface of the thyroid lobe in both the fresh and fixed states, contrary to most previous reports. The location of the ZT should be established in the anatomical position to avoid confusion.

Distribution of the internal branch of the human accessory nerve.

It was recently reported that the internal branch of the accessory nerve not only comprises the cranial root but also various combinations of the cranial root, spinal root, and the vagal component of the vagus nerve. The aim of this study was to demonstrate the anatomical distribution of each component of the internal branch of the human accessory nerve. Ten half-heads and necks of adult cadavers were used. The internal branch of the accessory nerve had three courses: the pharyngeal branch, the descending branch to the thorax, and the recurrent laryngeal nerve. The pharyngeal branch of the internal branch originated mainly from the vagus nerve, rather than from the cranial root of the accessory nerve. All of the components of the internal branch descended to the thorax along the vagus nerve. The recurrent laryngeal nerve comprised the internal branch and the vagus nerve in all specimens, and it was separated into bundles originating from the internal branch and vagus nerve. Both bundles gave off branches to the trachea and esophagus. The laryngeal distribution of the internal branch and vagus nerve was confirmed in the posterior cricoarytenoid, lateral cricoarytenoid, and thyroarytenoid muscles. These three laryngeal muscles were innervated by the cranial root and/or vagus nerve, but the distribution pattern was different in each specimen. Although the vagus nerve and cranial root are morphologically distinct nerves in the cranial cavity, they can be regarded functionally as the same nerve based on their distribution in the laryngeal muscles.

Rare communication between the musculocutaneous and median nerves in the forearm: its clinical significance.

Morphologic classifications of communication between musculocutaneous and median nerves are not based on the distribution and the function of the communicating branch. The authors report a rare case of such a communication with passage of the median nerve through the pronator teres muscle and discuss its clinical significance. The musculocutaneous nerve was divided into a lateral branch that continued to the lateral antebrachial cutaneous nerve and a medial branch that joined the median nerve in the forearm. The authors separated the nerve bundles and noted that the communicating branch derived from the sixth to seventh cervical nerves and supplied nerve fibers to the pronator teres muscle and the proper palmar digital nerve of the thumb. In addition, the median nerve penetrated the humeral head of the pronator teres muscle. Isolated musculocutaneous neuropathy with such a communication may cause unexpected symptoms such as sensory deficit in the palm and muscular weakness of the forearm and the thumb.

Morphological characteristics of the cranial root of the accessory nerve.

There has been the controversy surrounding the cranial root (CR) of the accessory nerve. This study was performed to clarify the morphological characteristics of the CR in the cranial cavity. Fifty sides of 25 adult cadaver heads were used. The accessory nerve was easily distinguished from the vagus nerve by the dura mater in the jugular foramen in 80% of 50 specimens. The trunk of the accessory nerve from the spinal cord penetrated the dura mater at various distances before entering the jugular foramen. In 20% of the specimens there was no dural boundary. In these cases, the uppermost cranial rootlet of the accessory nerve could be identified by removing the dura mater around the jugular foramen where it joined to the trunk of the accessory nerve at the superior vagal ganglion. The cranial rootlet was formed by union of two to four short filaments emerging from the medulla oblongata (66%) and emerged single, without filament (34%), and usually joined the trunk of the accessory nerve directly before the jugular foramen. The mean number of rootlets of the CR was 4.9 (range 2-9) above the cervicomedullary junction. The CR of the accessory nerve was composed of two to nine rootlets, which were formed by the union of two to four short filaments and joined the spinal root of the accessory nerve. The CR is morphologically distinct from the vagus nerve, confirming its existence.

Variable composition of the internal and external branches of the accessory nerve.

The purpose of this study was to clarify the composition of the internal and external branches (IB and EB) of the accessory nerve. Fifty-seven half heads of 34 adult cadavers were used. The IB and EB of the accessory nerve were mixed with the cranial root (CR), vagus nerve, and spinal root (SR). The IB was classified into five types and the EB into four types according to their composition. The IB consisted of only CR in 7.0% of the 57 cases, and of the CR and the vagus nerve in 52.6%; the IB did not exist in 12.3%. The EB was only composed of the SR in 19.3% of cases, the SR and CR in 52.6%, and the SR, CR, and the vagus nerve in 21.1%. There were 14 combinations of IB and EB types. The most common combination was the IB with the CR and the vagus nerve, and the EB with the SR and CR (31.6%). The combination of IB and EB comprising CR and SR, respectively, was not observed. The IB and EB are known to consist of the CR and SR of the accessory nerve, respectively. However, this study shows that there are no IB and EB comprising only the CR and SR, respectively, and the branches have various combinations of the CR, SR, and vagus nerve.

Expression of Toll-like receptor 4, CD14, and NF-κB in Chinese patients with ulcerative colitis.

This study elucidates the significance of Toll-like receptor 4 (TLR4), CD14, and nuclear factor (NF)-κB on the pathogenesis of ulcerative colitis (UC). Colonic biopsy specimens were collected from active UC and controls. The expression of TLR4, CD14, and NF-κBp 65 was analyzed by immunohistochemistry (IHC) and reverse-transcription polymerase chain reaction (RT-PCR). In UC, disease activity index (DAI) and pathological grade were classified according to the Powell-Tuck grade system and Truelove-Richards system, respectively. Fifty-six UC cases and 56 controls entered the investigation. IHC and RT-PCR revealed a significant increase of TLR4, CD14, and NF-κBp 65 antigen expression in colonic mucosa of UC compared with colonic mucosa of controls (p < .001). In UC, TLR4, CD14, and NF-κBp 65 expression were positively related to DAI (r = .873, p < .001; r = .576, p < .001; r = .747, p < .001 receptively). NF-κBp65 significantly correlated with TLR4 and CD14 (r = .669, p < .001; r = .576, p < .001, receptively). TLR4, CD14, and NF-κBp65 were positively related to pathological classification in UC (p < .01). Thus, TLR4, CD14, and NF-κBp65 were upregulated significantly in UC, to an extent that reflects the degree of inflammation and thereby might contribute to the occurrence and development of UC.