Spatial proteomics of immune microenvironment in nonalcoholic steatohepatitis-associated hepatocellular carcinoma.

BACKGROUND AND AIMS: NASH-HCC is inherently resistant to immune checkpoint blockade, but its tumor immune microenvironment is largely unknown. APPROACH AND RESULTS: We applied the imaging mass cytometry to construct a spatially resolved single-cell atlas from the formalin-fixed and paraffin-embedded tissue sections from patients with NASH-HCC, virus-HCC (HBV-HCC and HCV-HCC), and healthy donors. Based on 35 biomarkers, over 750,000 individual cells were categorized into 13 distinct cell types, together with the expression of key immune functional markers. Higher infiltration of T cells, myeloid-derived suppressor cell (MDSCs), and tumor-associated macrophages (TAMs) in HCC compared to controls. The distribution of immune cells in NASH-HCC is spatially heterogeneous, enriched at adjacent normal tissues and declined toward tumors. Cell-cell connections analysis revealed the interplay of MDSCs and TAMs with CD8 + T cells in NASH-HCC. In particular, exhausted programmed cell death 1 (PD-1 + )CD8 + T cells connected with programmed cell death-ligand 1 (PD-L1 + )/inducible T cell costimulator (ICOS + ) MDSCs and TAMs in NASH-HCC, but not in viral HCC. In contrast, CD4 + /CD8 + T cells with granzyme B positivity were reduced in NASH-HCC. Tumor cells expressed low PD-L1 and showed few connections with immune cells. CONCLUSIONS: Our work provides the first detailed spatial map of single-cell phenotypes and multicellular connections in NASH-HCC. We demonstrate that interactions between MDSCs and TAMs with effector T cells underlie immunosuppression in NASH-HCC and are an actionable target.

The effects of ARID1A mutation in gastric cancer and its significance for treatment.

Gastric cancer (GC) has emerged as a significant issue in public health all worldwide as a result of its high mortality rate and dismal prognosis. AT-rich interactive domain 1 A (ARID1A) is a vital component of the switch/sucrose-non-fermentable (SWI/SNF) chromatin remodeling complex, and ARID1A mutations occur in various tumors, leading to protein loss and decreased expression; it then affects the tumor biological behavior or prognosis. More significantly, ARID1A mutations will likely be biological markers for immune checkpoint blockade (ICB) treatment and selective targeted therapy. To provide theoretical support for future research on the stratification of individuals with gastric cancer with ARID1A as a biomarker to achieve precision therapy, we have focused on the clinical significance, predictive value, underlying mechanisms, and possible treatment strategies for ARID1A mutations in gastric cancer in this review.

MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor.

BACKGROUND: The Mitogen-activated protein kinase 1 (MAPK1) has both independent functions of phosphorylating histones as a kinase and directly binding the promoter regions of genes to regulate gene expression as a transcription factor. Previous studies have identified elevated expression of MAPK1 in human gastric cancer, which is associated with its role as a kinase, facilitating the migration and invasion of gastric cancer cells. However, how MAPK1 binds to its target genes as a transcription factor and whether it modulates related gene expressions in gastric cancer remains unclear. RESULTS: Here, we integrated biochemical assays (protein interactions and chromatin immunoprecipitation (ChIP)), cellular analysis assays (cell proliferation and migration), RNA sequencing, ChIP sequencing, and clinical analysis to investigate the potential genomic recognition patterns of MAPK1 in a human gastric adenocarcinoma cell-line (AGS) and to uncover its regulatory effect on gastric cancer progression. We confirmed that MAPK1 promotes AGS cells invasion and migration by regulating the target genes in different directions, up-regulating seven target genes (KRT13, KRT6A, KRT81, MYH15, STARD4, SYTL4, and TMEM267) and down-regulating one gene (FGG). Among them, five genes (FGG, MYH15, STARD4, SYTL4, and TMEM267) were first associated with cancer procession, while the other three (KRT81, KRT6A, and KRT13) have previously been confirmed to be related to cancer metastasis and migration. CONCLUSION: Our data showed that MAPK1 can bind to the promoter regions of these target genes to control their transcription as a bidirectional transcription factor, promoting AGS cell motility and invasion. Our research has expanded the understanding of the regulatory roles of MAPK1, enriched our knowledge of transcription factors, and provided novel candidates for cancer therapeutics.

A micro-vibration-driven direct ink write printing method of gallium-indium alloys.

Combining liquid fluidity and metallic conductivity, gallium-indium (Ga-In) alloys are making a splash in areas such as stretchable electronic circuits and wearable medical devices. Due to high flexibility, direct ink write printing is already widely employed for printing Ga-In alloys. Currently, pneumatic extrusion is the main method of direct ink write printing, but the oxide skin and low viscosity of the Ga-In alloys make it challenging to control after extrusion. This work proposed a method for direct ink write printing of Ga-In alloys utilizing micro-vibration-driven extrusion. Micro-vibration reduces the surface tension of Ga-In alloy droplets and avoids the appearance of random droplets during printing. Under micro-vibration, the nozzle tip pierces the oxide skin to form small droplets which have a high moldability. The droplet growth process is significantly slowed down by optimizing suitable micro-vibration parameters. Therefore, the Ga-In alloy droplets with high moldability can be maintained at the nozzle for a long period, which improves printability. Furthermore, better printing outcomes were obtained with micro-vibrations by choosing the proper nozzle height and printing speed. Experiment results demonstrated the superiority of the method in terms of Ga-In alloys extrusion control. With this method, the printability of the liquid metals is enhanced.

Complete mitochondrial genome of Kentrochrysalis streckeri (Lepidoptera: Sphingidae) and phylogenetic analysis.

In this study, we sequenced the complete mitogenome of Kentrochrysalis streckeri (Staudinger, 1880). The complete mitogenome sequence of K. streckeri is circular, 15,253 bp in size and contains 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a control region (CR). Nucleotide composition was A + T biased, and all the PCGs exhibited a positive AT-skew, which was reflected in the nucleotide composition, codon, and amino acid usage. Most PCGs start with ATG or ATT and stop with TAA. However, COX1 gene starts with CGA and three genes (COX1, COX2, NAD5) use the incomplete stop codon T. Phylogenetic analyses showed that the relationship (K. streckeri+((Manduca sexta+Sphinx morio)+(Psilogramma increta+(Psilogramma menephron+Notonagemia analis scribae)))).

Migraines and keloids: a 15-year Taiwan claim database analysis.

BACKGROUND: Fibroproliferative lesions with intractable pruritus, pain and hyperesthesia that cause uncontrolled scar growth are known as keloids. Migraines are common upsetting headache disorders characterised by frequent recurrence and attacks aggravated by physical activity. Both keloids and migraines can cause physical exhaustion and discomfort in patients; they have similar pathophysiological pathways, that is, the transforming growth factor-ß1 gene and neurogenic inflammation. OBJECTIVE: To investigate subsequent development of migraines in patients with keloids. Methods Data were retrieved from the Taiwan National Health Insurance Research Database. The keloids group included patients aged 20 years and older with a recent diagnosis of keloids(n=9864). The non-keloids group included patients without keloids matched for gender and age at 1-4 ratio (n=39 456). Migraine risk between groups was measured by Cox proportional hazards regression models. Incidence rates and hazard ratios were calculated. RESULTS: During the study period, 103 keloids patients and 323 non-keloids patients developed migraines. The keloids patients had a 2.29-fold greater risk of developing migraines compared with the non-keloids group after adjustment for covariates (1.81 vs 0.55 per 1000 person-years, respectively). In the keloids group, female or patients younger than 50 years were prone to developing migraines. CONCLUSION: The higher tendency to develop migraines in the keloids group in comparison with the non-keloids group suggests that keloids could be a predisposing risk factor for migraine development in adults. Keloids patients who complain of headaches should be examined for migraines.

The association between keloid and osteoporosis: real-world evidence.

BACKGROUND: Keloids are characterized by disturbance of fibroblast proliferation and apoptosis, deposition of collagen, and upregulation of dermal inflammation cells. This benign dermal fibro-proliferative scarring condition is a recognized skin inflammation disorder. Chronic inflammation is a well-known contributor to bone loss and its sequelae, osteoporosis. They both shared a similar pathogenesis through chronic inflammation. We assessed whether keloids increase osteoporosis risk through using National Health Insurance Research Database. METHODS: The 42,985 enrolled patients included 8597 patients with keloids but no history of osteoporosis; 34,388 controls without keloids were identified from the general population and matched at a one-to-four ratio by age, gender. Kaplan-Meier method was applied to determine cumulative incidence of osteoporosis. Cox proportional hazard regression analysis was performed after adjustment of covariates to estimate the effect of keloids on osteoporosis risk. RESULTS: Of the 8597 patients with keloids, 178 (2.07%) patients were diagnosed with osteoporosis while in the 34,388 controls, 587 (1.71%) were diagnosed with osteoporosis. That is, the keloids patients had 2.64-fold higher risk of osteoporosis compared to controls after adjustment for age, gender, Charlson Comorbidity Index and related comorbidities. The association between keloids and osteoporosis was strongest in patients younger than 50 years (hazard ratio = 7.06%) and in patients without comorbidities (hazard ratio = 4.98%). In the keloids patients, a high incidence of osteoporosis was also associated with advanced age, high Charlson Comorbidity Index score, hyperlipidemia, chronic liver disease, stroke, and depression. CONCLUSIONS: Osteoporosis risk was higher in patients with keloids compared to controls, especially in young subjects and subjects without comorbidities.

Stroke and osteoporosis: a Taiwan cohort study.

BACKGROUND: Osteoporosis and stroke are major health problems that have potentially overlapping pathophysiological mechanisms. The aim of this study was to estimate osteoporosis risk in Taiwan patientswho had a stroke. METHOD: This study retrieved data contained in the Taiwan National Health Insurance Research Database for a population-based sample of consecutive patients either hospitalised for stroke or treated for stroke on an outpatient basis. A total of 7550 newly diagnosed patientswho had a stroke were enrolled during 1996-2010. Osteoporosis risk in these patients was then compared with a matched group of patients who had not had a stroke randomly selected from the database at a ratio of 1:4 (n=30 200). The relationship between stroke history and osteoporosis risk was estimated with Cox proportional hazard regression models. RESULTS: During the follow-up period, osteoporosis developed in 1537 patients who had a stroke and in 5830 patients who had not had a stroke. The incidence of osteoporosis for cohorts with and without stroke was 32.97 and 14.28 per 1000 person-years, respectively. After controlling for covariates, the overall risk of osteoporosis was 1.82-fold higher in the stroke group than in the non-stroke group. The relative osteoporosis risk contributed by stroke had apparently greater impact among male gender and younger age groups. CONCLUSION: History of stroke is a risk factor for osteoporosis in Taiwan. Much attention to stroke-targeted treatment modalities might minimise adverse outcomes of osteoporosis.

Association between suicide risk and traumatic brain injury in adults: a population based cohort study.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of death and disability worldwide, and its treatment is potentially a heavy economic burden. Suicide is another global public health problem and the second leading cause of death in young adults. Patients with TBI are known to have higher than normal rates of non-fatal deliberate self-harm, suicide and all-cause mortality. The aim of this study was to explore the association between TBI and suicide risk in a Chinese cohort. METHOD: This study analysed data contained in the Taiwan National Health Insurance Research Database for 17 504 subjects with TBI and for 70 016 subjects without TBI matched for age and gender at a ratio of 1 to 4. Cox proportional hazard regression analysis was used to estimate subsequent suicide attempts in the TBI group. Probability of attempted suicide was determined by Kaplan-Meier method. RESULTS: The overall risk of suicide attempts was 2.23 times higher in the TBI group compared with the non-TBI group (0.98 vs 0.29 per 1000 person-years, respectively) after adjustment for covariates. Regardless of gender, age or comorbidity, the TBI group tended to have more suicide attempts, and the risk attempted suicide increased with the severity of TBI. Depression and alcohol attributed disease also increased the risk of attempted suicide in the TBI group. CONCLUSION: Suicide is preventable if risk factors are recognised. Hence, TBI patients require special attention to minimise their risk of attempted suicide.

One new sterpurane sesquiterpene from cultures of the basidiomycete Pholiota nameko.

One new sterpurane sesquiterpene (1), named (3R,6S,7S,8R,10S)-3,7,14-trihydroxy-1-sterpurene was isolated from cultures of the basidiomycete Pholiota nameko. The structure of new compound was elucidated by extensive spectroscopic. Additionally, a single crystal X-ray diffraction not only confirmed the structure, but also determined the absolute configuration of the new compound. The compound was evaluated for cytotoxicity against five human cancer cell lines, but no significant cytotoxicity were found (IC50 values > 40 µM).

Effects of Temperature on the Tribological Properties of NM600 under Sliding Wear.

An investigation on the tribological properties of GCr15 sliding against NM600 was carried out using a high-temperature friction and wear tester. As the temperature rose from room temperature to 300 °C, the average friction coefficient of NM600 increased rapidly, then decreased rapidly, and then became stable. The wear volume and specific wear rate of NM600 increased rapidly, then decreased rapidly, and then increased slowly. The wear mechanism and matrix properties of the tested steel at different temperatures are the main reasons for the above results. At 20-50 °C, the main wear mechanism was adhesive wear, fatigue wear, and abrasive wear. At 100-150 ℃, the wear mechanism was mainly adhesive wear, fatigue wear, abrasive wear, and oxidation wear. At 200-300 °C, the wear mechanism was mainly oxidation wear and abrasive wear.

Migraine and traumatic brain injury: a cohort study in Taiwan.

OBJECTIVE: Traumatic brain injury is now a major contributor to the global healthcare burden. Migraine is another debilitating disease with a global health impact. While most researchers agree that traumatic brain injury is a risk factor for migraine, whether migraine is a risk factor for traumatic brain injury still remains under debate. We therefore aimed to investigate whether migraine was a risk factor for developing traumatic brain injury. STUDY DESIGN: Retrospective population-based cohort study. SETTING: Data for people who had been diagnosed with migraine were retrieved from Taiwan's National Health Insurance Research Database. PARTICIPANTS: We identified 7267 patients with newly diagnosed migraine during 1996-2010. The migraineurs to non-migraineurs ratio was set at 1:4 to enhance the power of statistical tests. PRIMARY AND SECONDARY OUTCOME MEASURES: We used multivariate Cox proportional hazard regression models to assess the effects of migraines on the risk of traumatic brain injury after adjusting for potential confounders. RESULTS: The overall traumatic brain injury risk was 1.78 times greater in the migraine group compared with the non-migraine group after controlling for covariates. Additionally, patients with previous diagnoses of alcohol-attributed disease, mental disorders and diabetes mellitus had a significantly higher traumatic brain injury risk compared with those with no history of these diagnoses. CONCLUSIONS: This study of a population-based database indicated that migraine is a traumatic brain injury risk factor. Greater attention to migraine-targeted treatment modalities may reduce traumatic brain injury-related morbidity and mortality.

Efficacy of High Specific Volume Polysaccharide - A New Type of Dietary Fiber - On Molecular Mechanism of Intestinal Water Metabolism in Rats With Constipation.

BACKGROUND The aim of this study was to evaluate the effects of a new type of dietary fiber - high specific volume polysaccharide (HSVP) - on fecal properties, serum vasoactive intestinal peptide (VIP) concentration, intestinal flora count, and expression of the VIP-cAMP-PKA-AQP3 signaling pathway. MATERIAL AND METHODS Compound diphenoxylate was used in 48 healthy Wistar rats to establish a constipation model. Rats were divided into a normal control group, a constipation model group, an HSVP low-dose group, an HSVP medium-dose group, an HSVP high-dose group, and a fructose control group. We used colony count method, ELISA, WB, and RT-PCR to determine fecal moisture content, fecal hardness, fecal passage time, serum VIP concentration, number of intestinal bacteria, and VIP-cAMP-PKA-AQP3 signal pathway protein expression. RESULTS The constipation model was established successfully. HSVP (the medium dose was 10% and the high dose was 15%) improved fecal moisture content, reduced hardness, shortened fecal emptying time, increased intestinal bacteria, reduced serum VIP concentration, downregulated cAMP and PKAm RNA transcription, reduced protein expression, and reduced intestinal AQP3 expression. CONCLUSIONS HSVP improved constipation, increased the number of intestinal bacteria, and elevated expression of the VIP-cAMP-PKA-AQP3 signaling pathway. The mechanism of HSVP in regulating intestinal water metabolism in constipated rats may occur through the VIP-cAMP-PKA-AQP3 signaling pathway, and be closely related to changes in intestinal bacteria. The important role of the brain-gut-microbiome axis in the pathogenesis of constipation has been confirmed in this study.

Emerging roles of circular RNAs in colorectal cancer.

Circular RNAs (circRNAs) are a newly discovered class of endogenous non-coding RNAs. Owing to the development of high-throughput sequencing, researchers have identified thousands of circRNAs. Emerging evidence suggests that circRNAs are involved in various tumor cell processes, including proliferation, apoptosis, invasion and migration. Because of their high stability and abundance, tissue-specific expression, and easy detection, circRNAs are considered ideal biomarkers for cancer diagnosis and prognosis. An increasing number of studies have recently demonstrated that circRNAs are closely associated with colorectal cancer (CRC). CRC is the third most common cancer and the second leading cause of cancer-related death globally. Thus, understanding the molecular mechanisms involved in the development and progression of CRC is vital. In this review, we summarize the current literature regarding human circRNAs related to CRC and present an overview of the potential clinical implications of circRNAs with respect to CRC.

Current Status of Functional Studies on Circular RNAs in Bladder Cancer and their Potential Role as Diagnostic and Prognostic Biomarkers: A Review.

d_abstr_R Worldwide, bladder cancer represents the ninth most common malignancy and is the 13th cause of cancer-associated death. Although surgery combined with chemotherapy and radiotherapy has improved patient outcomes, the prognosis remains poor for most patients with muscle-invasive bladder cancer. The exact mechanisms and critical regulators of bladder cancer remain unknown. Circular RNAs (circRNAs) are a distinct type of endogenous non-coding RNA. Recent studies have shown that circRNAs participate in many processes, including proliferation, invasion, migration, and apoptosis in multiple types of malignancy, including bladder cancer. Some circRNAs are dysregulated in bladder cancer and play essential roles in cancer progression. Importantly, some circRNAs may serve as diagnostic and prognostic biomarkers for bladder cancer. This review aims to summarize the findings from recent studies that have focused on the roles of human circRNAs in bladder cancer and discusses the clinical roles for circRNAs, including their potential roles as diagnostic or prognostic biomarkers.

Keloid risk in patients with atopic dermatitis: a nationwide retrospective cohort study in Taiwan.

OBJECTIVE: The pathogenesis of keloid is largely unknown. Because keloid and atopic dermatitis have overlapping pathophysiological mechanisms, we aimed to evaluate keloid risk in patients with atopic dermatitis. STUDY DESIGN: Population-based retrospective cohort study. SETTING: The Taiwan National Health Insurance Research Database was used to analyse data for people who had been diagnosed with atopic dermatitis. PARTICIPANTS: We identified 8371 patients with newly diagnosed atopic dermatitis during 1996-2010. An additional 33 484 controls without atopic dermatitis were randomly identified and frequency matched at a one-to-four ratio. PRIMARY AND SECONDARY OUTCOME MEASURE: The association between atopic dermatitis and keloid risk was estimated using Cox proportional hazard regression models. RESULTS: After adjustment for covariates, the atopic dermatitis patients have a 3.19-fold greater risk of developing keloid compared with the non-atopic dermatitis group (3.19vs1.07 per 1000 person-years, respectively). During the study period, 163 patients with atopic dermatitis and 532 patients without atopic dermatitis developed keloid. Notably, keloid risk increased with severity of atopic dermatitis, particularly in patients with moderate to severe atopic dermatitis. CONCLUSIONS: Our results indicate that patients with atopic dermatitis had a higher than normal risk of developing keloid and suggest that atopic dermatitis may be an independent risk factor for keloid.

Thermo-Electric Properties of Cu and Ni Nanoparticles Packed Beds.

The hot-wire method and the four-probe resistivity method are applied to probe the thermal conductivity (k) and the electric conductivity (σ) of Cu and Ni nanoparticle packed beds (NPBs). A fitting method based on classical physical theory is devised to separate ke (electronic thermal conductivity) and kp (phonon thermal conductivity) from k at room temperature. Results turn out that kp only accounts for a small proportion of k (4-20%); the proportion decreases with increasing porosity or temperature. Most importantly, this fitting method provides a simple way to separate ke and kp from k at room temperature. The Wiedemann-Franz law is checked and is found to be unsuitable for NPBs. The Lorenz number (L) is calculated from measurements of ke, k, and σ. Results turn out that L is found to be 50-60 times that of the bulk. With a Seebeck coefficient (S) measured, the thermoelectric property of NPBs is also calculated. We find that the NPB possess an advantage in thermoelectric property than bulk, the thermoelectric figure of merit (ZT) of Ni (Cu) NPBs can be 20.17 (1.87) times that of bulk Ni (Cu). The effect of porosity on ZT is also discussed, and results show that a NPB with a small porosity is more preferable as a thermoelectric material. With a small porosity, ZT can be even 1.73 times that of a large porosity. Although metals are not good thermoelectric material, the method in this paper supplies a way to improve the thermoelectric property of other thermoelectric materials.

Experimental Study on Thermal Conductivity and Hardness of Cu and Ni Nanoparticle Packed Bed for Thermoelectric Application.

The hot-wire method is applied in this paper to probe the thermal conductivity (TC) of Cu and Ni nanoparticle packed beds (NPBs). A different decrease tendency of TC versus porosity than that currently known is discovered. The relationship between the porosity and nanostructure is investigated to explain this unusual phenomenon. It is found that the porosity dominates the TC of the NPB in large porosities, while the TC depends on the contact area between nanoparticles in small porosities. Meanwhile, the Vickers hardness (HV) of NPBs is also measured. It turns out that the enlarged contact area between nanoparticles is responsible for the rapid increase of HV in large porosity, and the saturated nanoparticle deformation is responsible for the small increase of HV in low porosity. With both TC and HV considered, it can be pointed out that a structure of NPB with a porosity of 0.25 is preferable as a thermoelectric material because of the low TC and the higher hardness. Although Cu and Ni are not good thermoelectric materials, this study is supposed to provide an effective way to optimize thermoelectric figure of merit (ZT) and HV of nanoporous materials prepared by the cold-pressing method.

Emerging Technologies and Synergies for Airborne and Space-Based Measurements of Water Vapor Profiles.

A deeper understanding of how clouds will respond to a warming climate is one of the outstanding challenges in climate science. Uncertainties in the response of clouds, and particularly shallow clouds, have been identified as the dominant source of the discrepancy in model estimates of equilibrium climate sensitivity. As the community gains a deeper understanding of the many processes involved, there is a growing appreciation of the critical role played by fluctuations in water vapor and the coupling of water vapor and atmospheric circulations. Reduction of uncertainties in cloud-climate feedbacks and convection initiation as well as improved understanding of processes governing these effects will result from profiling of water vapor in the lower troposphere with improved accuracy and vertical resolution compared to existing airborne and space-based measurements. This paper highlights new technologies and improved measurement approaches for measuring lower tropospheric water vapor and their expected added value to current observations. Those include differential absorption lidar and radar, microwave occultation between low-Earth orbiters, and hyperspectral microwave remote sensing. Each methodology is briefly explained, and measurement capabilities as well as the current technological readiness for aircraft and satellite implementation are specified. Potential synergies between the technologies are discussed, actual examples hereof are given, and future perspectives are explored. Based on technical maturity and the foreseen near-mid-term development path of the various discussed measurement approaches, we find that improved measurements of water vapor throughout the troposphere would greatly benefit from the combination of differential absorption lidar focusing on the lower troposphere with passive remote sensors constraining the upper-tropospheric humidity.

Influence of Nanopore Shapes on Thermal Conductivity of Two-Dimensional Nanoporous Material.

The influence of nanopore shapes on the electronic thermal conductivity (ETC) was studied in this paper. It turns out that with same porosity, the ETC will be quite different for different nanopore shapes, caused by the different channel width for different nanopore shapes. With same channel width, the influence of different nanopore shapes can be approximately omitted if the nanopore is small enough (smaller than 0.5 times EMFP in this paper). The ETC anisotropy was discovered for triangle nanopores at a large porosity with a large nanopore size, while there is a similar ETC for small pore size. It confirmed that the structure difference for small pore size may not be seen by electrons in their moving.