Suppressed thermal transport in silicon nanoribbons by inhomogeneous strain.

Nanoscale structures can produce extreme strain that enables unprecedented material properties, such as tailored electronic bandgap1-5, elevated superconducting temperature6,7 and enhanced electrocatalytic activity8,9. While uniform strains are known to elicit limited effects on heat flow10-15, the impact of inhomogeneous strains has remained elusive owing to the coexistence of interfaces16-20 and defects21-23. Here we address this gap by introducing inhomogeneous strain through bending individual silicon nanoribbons on a custom-fabricated microdevice and measuring its effect on thermal transport while characterizing the strain-dependent vibrational spectra with sub-nanometre resolution. Our results show that a strain gradient of 0.112% per nanometre could lead to a drastic thermal conductivity reduction of 34 ± 5%, in clear contrast to the nearly constant values measured under uniform strains10,12,14,15. We further map the local lattice vibrational spectra using electron energy-loss spectroscopy, which reveals phonon peak shifts of several millielectron-volts along the strain gradient. This unique phonon spectra broadening effect intensifies phonon scattering and substantially impedes thermal transport, as evidenced by first-principles calculations. Our work uncovers a crucial piece of the long-standing puzzle of lattice dynamics under inhomogeneous strain, which is absent under uniform strain and eludes conventional understanding.

Efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes uncontrolled with metformin: PIONEER 12, a double-blind, Phase IIIa, randomised trial.

AIMS/HYPOTHESIS: The aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. METHODS: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS). RESULTS: Of 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were -2 (-4, -1) mmol/mol, -8 (-9, -6) mmol/mol and -11 (-12, -9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were -0.2 (-0.3, -0.1), -0.7 (-0.8, -0.6) and -1.0 (-1.1, -0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] -0.9 [-1.4, -0.4] kg, -2.3 [-2.8, -1.8] kg and -3.3 [-3.8, -2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity. CONCLUSIONS/INTERPRETATION: Significantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials. TRIAL REGISTRATION: ClinicalTrials.gov NCT04017832. FUNDING: This trial was funded by Novo Nordisk A/S, Søborg, Denmark.

Efficient Photoelectrochemical Hydrogen Generation Based on Core Size Effect of Heterostructured Quantum Dots.

Colloidal quantum dots (QDs) are shown to be effective as light-harvesting sensitizers of metal oxide semiconductor (MOS) photoelectrodes for photoelectrochemical (PEC) hydrogen (H2) generation. The CdSe/CdS core/shell architecture is widely studied due to their tunable absorption range and band alignment via engineering the size of each composition, leading to efficient carrier separation/transfer with proper core/shell band types. However, until now the effect of core size on the PEC performance along with tailoring the core/shell band alignment is not well understood. Here, by regulating four types of CdSe/CdS core/shell QDs with different core sizes (diameter of 2.8, 3.1, 3.5, and 4.8 nm) while the thickness of CdS shell remains the same (thickness of 2.0 ± 0.1 nm), the Type II, Quasi-Type II, and Type I core/shell architecture are successfully formed. Among these, the optimized CdSe/CdS/TiO2 photoelectrode with core size of 3.5 nm can achieve the saturated photocurrent density (Jph) of 17.4 mA cm-2 under standard one sun irradiation. When such cores are further optimized by capping alloyed shells, the Jph can reach values of 22 mA cm2 which is among the best-performed electrodes based on colloidal QDs.

The effect of novel aromatic heterocycle substituted aminamidine derivatives on Necator americanus.

BACKGROUND: The efficacy of current drugs against hookworms at a single dose is highly variable across regions, age groups and infection intensity. Extensive and repeated use of these drugs also leads to potential drug resistance. Therefore, novel drugs are required for sustained disease control. OBJECTIVES: Novel aromatic heterocycle substituted aminamidine derivatives (AADs) were synthesized based on tribendimine (TBD), and their in vivo potency against Necator americanus was tested. METHODS: The efficacy of the AADs was tested in male hamsters. Oral and IV pharmacokinetic parameters were determined in male Sprague-Dawley rats. The proteomic profiles of N. americanus samples treated with AADs were compared using tandem mass tag-based quantitative proteomic analyses. RESULTS: Most AADs exhibited better anthelmintic activity than TBD at a single oral dose. Compound 3c exhibited improved solubility (>50×), and the curative dose was as low as 25 mg/kg. Similar to TBD, 3c was rapidly metabolized after oral administration and transformed into p-(1-dimethylamino ethylimino)aniline (dADT), an active metabolite against intestinal nematodes. dADT from 3c had better pharmacokinetic profiles than that from TBD and achieved an oral bioavailability of 99.5%. Compound 3c possessed rapid anthelmintic activity, clearing all worms within 24 h after an oral dose of 50 mg/kg. Quantitative proteomic analysis indicated that it might be related to ATP metabolism and cuticle protein synthesis. CONCLUSIONS: Compound 3c is a novel and promising compound against N. americanus in vivo.

Reexamination of Damping in Sliding Friction.

Friction is responsible for about one-third of the primary energy consumption in the world. So far, a thorough atomistic understanding of the frictional energy dissipation mechanisms is still lacking. The Amontons' law states that kinetic friction is independent of the sliding velocity while the Prandtl-Tomlinson model suggests that damping is proportional to the relative sliding velocity between two contacting objects. Through careful analysis of the energy dissipation process in atomic force microscopy measurements, here we propose that damping force is proportional to the tip oscillation speed induced by friction. It is shown that a physically well-founded damping term can better reproduce the multiple peaks in the velocity-dependent friction force observed in both experiments and molecular dynamics simulations. Importantly, the analysis gives a clear physical picture of the dynamics of energy dissipation in different friction phases, which provides insight into long-standing puzzles in sliding friction, such as velocity weakening and spring-stiffness-dependent friction.

Stereoselective Crystallization of Chiral Pharmaceuticals Aided by Cellulose Derivatives through Helical Pattern Matching.

Stereoselective inhibition aided by "tailor-made" polymeric additives is an efficient approach to obtain enantiopure compounds through conglomerate crystallization. The chemical and configurational match between the side groups of polymers and the molecules of undesired enantiomer is considered to be a necessary condition for successful stereoseparation. Whereas in this contribution, we present an effective resolution of chiral pharmaceuticals by using cellulose acetates as the additives, which stereoselectively reside on the specific crystal faces of one enantiomer and inhibit its crystal nucleation and growth through helical pattern and supramolecular interaction complementarity. An investigation of nimodipine serves as a case study to highlight the novelty of this strategy wherein R-crystals exhibiting an impressive enantiomeric excess value of 97% can be attained by employing a mere 0.01 wt% cellulose acetate. Guaifenesin and phenyl lactic acid are also well-resolved by utilizing this methodology. Our work not only brings about a brand-new design strategy for "tailor-made" additives, but will also promote the further exploration of the endless potential for utilizing natural biomolecules in chiral recognition and resolution.

Real-world advantage and challenge of post-autologous stem cell transplantation MRD negativity in high-risk patients with double-hit multiple myeloma.

BACKGROUND: Autologous stem-cell transplantation (ASCT) remains a beneficial approach for patients with newly diagnosed multiple myeloma (NDMM) in the age of novel therapeutic agents. Nevertheless, limited real-world data is available to establish criteria for identifying high-risk ASCT patients. METHODS: We analyzed outcomes for 168 NDMM patients who underwent ASCT at our center from December 2015 to December 2022. We investigated the impact of the number of high-risk cytogenetics (HRCA), defined as t(4;14), t(14;16), 1q21 gain/amplification, and del(17p), as well as the post-ASCT minimal residual disease (MRD) status as prognostic indicators. We assessed progression-free survival (PFS) and overall survival (OS), and focused on identifying risk factors. RESULTS: The cohort included 42% of patients (n = 71) with 0 HRCA, 42% (n = 71) with 1 HRCA, and 16% (n = 26) with ≥ 2 HRCA. After a median follow-up of 31 months, the median PFS was 53 months (95% CI, 37-69), and OS was not reached for the entire cohort. Despite similar rates of MRD-negativity post-ASCT, patients with ≥ 2 HRCA, termed "double hit" (DH), had a significantly higher risk of progression/mortality than those with 0 or 1 HRCA. Multivariate analysis highlighted DH (HR 4.103, 95% CI, 2.046-8.231) and MRD positivity post-ASCT (HR 6.557, 95% CI, 3.217-13.366) as adverse prognostic factors for PFS, with DH also linked to inferior OS. As anticipated, DH patients with post-ASCT MRD positivity displayed the poorest prognosis, with a median PFS of 7 months post-ASCT. Meanwhile, DH patients with MRD negativity post-ASCT showed improved prognosis, akin to MRD-negative non-DH patients. It is noteworthy to exercise caution, as DH patients who initially achieved MRD negativity experienced a 41% cumulative loss of that status within one year. CONCLUSIONS: This study strongly advocates integrating DH genetic assessments for eligible ASCT patients and emphasizes the importance of ongoing MRD monitoring, as well as considering MRD-based treatment adaptation for those patients in real-world settings.

Phonon energy dissipation in friction between black phosphorus layers.

Herein, we employ molecular dynamics simulations to decode the friction properties and phonon energy dissipation between black phosphorus layers. The observations reveal the influence of three factors, temperature, velocity, and normal load, on the friction force of monolayer/bilayer black phosphorus. Specifically, friction is negatively correlated with layer thickness and temperature, and positively correlated with velocity and normal load. The change in friction force is further explained in terms of frictional energy dissipation, and supplemented by the height of potential barriers as well as the number of excited phonons. From the phonon spectrum analysis, the phonon number at the contact interface is found to be higher than that at the non-contact interface. This is due to the larger distance of the contact interface atoms deviate from their equilibrium positions, resulting in higher total energy generated by more intense oscillations, and therefore contributes greater to friction.

Langerhans cell histiocytosis in children with refractory diarrhoea and hypoalbuminaemia as the initial presentation: two case reports and a literature review.

Langerhans cell histiocytosis (LCH) involving the gastrointestinal tract is a rare condition for which clinical experience is limited. We describe the cases of two patients who initially presented with chronic diarrhoea, hypoproteinaemia, and intermittent fever. These findings suggest that in cases of refractory diarrhoea accompanied by recurrent hypoalbuminaemia, especially with abdominal rash, LCH should be considered. Gastrointestinal endoscopy, biopsy, and imaging studies are essential for obtaining a definitive diagnosis. This approach might be helpful for the early recognition of gastrointestinal tract involvement in LCH.

Ex vivo liver resection and auto-transplantation as an alternative for the treatment of liver malignancies: Progress and challenges.

Hepatectomy is still the major curative treatment for patients with liver malignancies. However, it is still a big challenge to remove the tumors in the central posterior area, especially if their location involves the retrohepatic inferior vena cava and hepatic veins. Ex vivo liver resection and auto-transplantation (ELRA), a hybrid technique of the traditional liver resection and transplantation, has brought new hope to these patients and therefore becomes a valid alternative to liver transplantation. Due to its technical difficulty, ELRA is still concentrated in a few hepatobiliary centers that have experienced surgeons in both liver resection and liver transplantation. The efficacy and safety of this technique has already been demonstrated in the treatment of benign liver diseases, especially in the advanced alveolar echinococcosis. Recently, the application of ELRA for liver malignances has gained more attention. However, standardization of clinical practice norms and international consensus are still lacking. The prognostic impact in these oncologic patients also needs further evaluation. In this review, we summarized the principles and recent progresses on ELRA.

CircEML1 facilitates the steroid synthesis in follicular granulosa cells of chicken through sponging gga-miR-449a to release IGF2BP3 expression.

Non-coding RNAs (ncRNAs) induced competing endogenous RNAs (ceRNA) play crucial roles in various biological process by regulating target gene expression. However, the studies of ceRNA networks in the regulation of ovarian ovulation processing of chicken remains deficient compared to that in mammals. Our present study revealed that circEML1 was differential expressed in hen's ovarian tissues at different ages (15 W/20 W/30 W/68 W) and identified as a loop structure from EML1 pre-mRNA, which promoted the expressions of CYP19A1/StAR and E2/P4 secretion in follicular granulosa cells (GCs). Furthermore, circEML1 could serve as a sponge of gga-miR-449a and also found that IGF2BP3 was targeted by gga-miR-449a to co-participate in the steroidogenesis, which possibly act the regulatory role via mTOR/p38MAPK pathways. Meanwhile, in the rescue experiment, gga-miR-449a could reverse the promoting role of circEML1 to IGF2BP3 and steroidogenesis. Eventually, this study suggested that circEML1/gga-miR-449a/IGF2BP3 axis exerted an important role in the steroidogenesis in GCs of chicken.

Optimization of the Zhou Tian Formula extraction technology based on AHP-CRITIC method and analysis of transfer efficiency of key components based on HPLC fingerprinting.

INTRODUCTION: Zhou Tian Formula (ZTF) is an antidepressant traditional Chinese medicine utilized widely in clinical settings for the treatment of patients with depression. However, shortcomings persist in its extraction technology and quality control. OBJECTIVE: This study aimed to propose a methodology for ZTF extraction technology based on the analytic hierarchy process (AHP)-criteria importance through intercriteria correlation (CRITIC) method and to establish a quality control framework for the efficient transfer of index components. METHOD: Firstly, we analyzed the chemical components of ZTF and determined the optimal extraction technology. Secondly, we calculated the transfer efficiency of the index components during the conversion of water decoction to extract powder and subsequently to granules. Thirdly, we established HPLC fingerprints for 15 batches of ZTF water decoction, extract powder, and granules. We employed SIMCA software to analyze the chemicals responsible for variations in quality among different batches of ZTF granules. RESULTS: We determined the optimal extraction process. The average transfer efficiency of ferulic acid, puerarin, mirificin, isoferulic acid, and calycosin during the conversion of water decoction to extract powder and subsequently to granules exceeded 41%. The HPLC fingerprints of ZTF exhibited a similarity exceeding 0.890. Variable importance in projection values indicated that calycosin, ferulic acid, and puerarin were the primary contributors to quality variations. CONCLUSIONS: The AHP-CRITIC method, coupled with an orthogonal array design, could be used for exploring extraction technology. In addition, the rules governing the transfer of index components from water decoction to extract powder, and subsequently to granules, could be applied for the evaluation and quality assessment of ZTF.

Surface Stoichiometry Control of Colloidal Heterostructured Quantum Dots for High-Performance Photoelectrochemical Hydrogen Generation.

Manipulating the separation and transfer behaviors of charges has long been pursued for promoting the photoelectrochemical (PEC) hydrogen generation based on II-VI quantum dot (QDs), but remains challenging due to the lack of effective strategies. Herein, a facile strategy is reported to regulate the recombination and transfer of interfacial charges through tuning the surface stoichiometry of heterostructured QDs. Using this method, it is demonstrated that the PEC cells based on CdSe-(Sex S1- x )4 -(CdS)2 core/shell QDs with a proper Ssurface /Cdsurface ratio exhibits a remarkably improved photocurrent density (≈18.4 mA cm-2 under one sun illumination), superior to the PEC cells based on QDs with Cd-rich or excessive S-rich surface. In-depth electrochemical and spectroscopic characterizations reveal the critical role (hole traps) of surface S atoms in suppressing the recombination of photogenerated charges, and further attribute the inferior performance of excessive S-rich QDs to the impeded charge transfer from QDs to TiO2 and electrolyte. This work puts forward a simple surface engineering strategy for improving the performance of QDs PEC cells, providing an efficient method to guide the surface design of QDs for their applications in other optoelectronic devices.

Detection and Characterization of In Vitro Payload-Containing Catabolites of Noncleavable Antibody-Drug Conjugates by High-Resolution Mass Spectrometry and Multiple Data Mining Tools.

The formation and accumulation of payload-containing catabolites (PCCs) from a noncleavable antibody-drug conjugate (ADC) in targeted and normal tissues are directly associated with the therapeutic effect and toxicity of the ADC, respectively. Understanding the PCC formation is important for supporting the payload design and facilitating preclinical evaluation of ADCs. However, detection and identification of PCCs of a noncleavable ADC are challenging due to their low concentrations and unknown structures. The main objective of this study was to develop and apply a generic liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method for profiling PCCs in vitro. Noncleavable ADCs, ado-trastuzumab emtansine (T-DM1) and ADC-1, were incubated in liver lysosomes, liver S9, and/or cancer cells followed by data acquisition using LC-HRMS. Profiling PCCs mainly relied on processing LC-HRMS datasets using untargeted precise and thorough background subtraction (PATBS) processing and targeted product ion filtering (PIF). As a result, 12 PCCs of T-DM1 were detected and structurally characterized in human liver lysosomal incubation, a majority of which consisted of 4-[N-maleimidomethyl]cyclohexane-1-carboxylate (MCC)-DM1 and a few amino acids. Additionally, the incubation of ADC-1 in human, rat, and monkey liver S9 and cancer cells generated one major and three very minor PCCs, verifying the payload design. The results demonstrate that PATBS enabled the comprehensive profiling of PCCs regardless of their molecular weights, charge states, and fragmentations. As a complementary tool, PIF detected specific PCCs with superior sensitivity. The combination of the in vitro metabolism systems and the LC-HRMS method is a useful approach to profiling in vitro PCCs of noncleavable ADCs in support of drug discovery programs. SIGNIFICANCE STATEMENT: Profiling in vitro payload-containing catabolites (PCCs) of a noncleavable antibody-drug conjugate (ADC) is important for optimization of the payload design and preclinical evaluation of ADC. However, currently used analytical approaches often fail to quickly provide reliable PCC profiling results. The work introduces a new liquid chromatography high resolution mass spectrometry method for comprehensive and rapid detection and characterization of PCCs released from a noncleavable ADC in liver lysosomes and S9 incubations.

Weak selection and stochastic evolutionary stability in a stochastic replicator dynamics.

It is a very challenging problem whether natural selection is able to effectively resist the continuous disturbance of environmental noise such that the direction or outcome of evolution determined by the deterministic selection pressure will not be changed. By analyzing the impact of weak selection on the evolutionary stability of a stochastic replicator dynamics with n possible pure strategies, we found that the weak selection is able to enhance the evolutionary stability, that is, under weak selection, the stochastic evolutionary stability of the system is determined by the mean payoff matrix. This finding strongly implies that the weak selection should be regarded as an important mechanism to ensure evolutionary stability in stochastic environments.

Total variation regularized expectation maximization reconstruction improves 68Ga-FAPI-04 PET/CT image quality as compared to ordered subset expectation maximization reconstruction.

BACKGROUND: This study aimed to investigate improvements in 68Ga-FAPI PET/CT image quality due to using total variation regularized expectation maximization (TVR-EM) and ordered subset expectation maximization (OS-EM) reconstruction. METHODS: Data from a total of 24 patients were retrospectively analyzed in this study. Positron emission tomography (PET) images were reconstructed using OS-EM and TVR-EM for 2 and 3 minutes-per-bed (min/bed) acquisition. The SUVmean of a region-of-interest on the liver, image noise, signal-to-noise ratios (SNR), the SUVmax of the lesions and the tumour-to-background ratios (TBR) were measured and compared between the 2 methods. Subjective image qualities were evaluated by two experienced radiologists using a 5-point score scale (5-excellent, 1-poor). RESULTS: In total, 132 lesions were analyzed. The image noise in TVR-EM reconstruction groups was lower than in the OS-EM groups (all P<0.05). The SNR, SUVmax of lesions and the TBR were higher for the TVR-EM reconstruction groups compared to OS-EM groups (all P<0.05). Also, the SUVmax of the lesions in the TVR-EM groups increased by at least 12% compared to OS-EM 3 min/bed group. The SUVmax for small (<10 mm) and large lesions (>10 mm) in the TVR-EM 2 min/bed group were significantly larger compared to the OS-EM 3 min/bed groups (all P<0.05). The highest image quality score resulted from the TVR-EM 3 min/bed group with a penalization factor of 0.25 (3.92±0.19). CONCLUSIONS: TVR-EM reduces image noise and improved the SNR, SUVmax and TBR of the lesions. It also enables fast acquisition without compromising image quality compared to standard OS-EM.

Equivalent cut-off values of Bath Ankylosing Spondylitis Disease Activity Index corresponding to Ankylosing Spondylitis Disease Activity Score cut-off values.

OBJECTIVES: To define the equivalent cut-off values of Bath ankylosing Spondylitis Disease Activity Index (BASDAI) for discriminating disease activity corresponding to Ankylosing Spondylitis Disease Activity Score (ASDAS) cut-off values, and to determine the equivalent change units for determining the clinically improvement between ΔBASDAI and ΔASDAS-CRP. METHODS: 475 patients with axial spondyloarthritis (axSpA) whose data on BASDAI and ASDAS were available were included. Among them, 154 (32.4%) patients whose data on ΔBASDAI and ΔASDAS-CRP were available. Receiver-operator curve (ROC) with area under curve (AUC) was used to determine the BASDAI cut-off values that best corresponded to ASDAS-CRP. The Cohen's kappa was utilised to assess the degree of agreement between disease activity states based on BASDAI and ASDAS cut-off values, and clinically improvement between ΔBASDAI and ΔASDAS-CRP. RESULTS: According to the ASDAS-CRP, 88 (18.6%), 130 (27.4%), 191 (40.1%) and 66 (13.9%) patients were classified as inactive, moderate, high and very high disease activities, respectively. ROC revealed that BASDAI values 1.6 (AUC: 0.948), 2.9 (AUC: 0.790) and 3.8 (AUC: 0.875) best corresponded to ASDAS-CRP values 1.3, 2.1 and 3.5, respectively. The degree of agreement between them was moderate (kappa: 0.527). The ΔBASDAI 1.6 (AUC: 0.745) and 2.0 (AUC: 0.708) best corresponded to the ΔASDAS-CRP 1.1 (minimal clinically important improvement) and 2.0 (major improvement), respectively. The degree of agreement was good (kappa: 0.685). CONCLUSIONS: The BASDAI values 1.6, 2.9 and 3.8 correspond to ASDAS-CRP values 1.3, 2.1 and 3.5, respectively. The ΔBASDAI 1.6 and 2.0 best correspond to the ΔASDAS-CRP 1.1 and 2.0, respectively.

Integrated transcriptome and miRNA sequencing analyses reveal that hypoxia stress induces immune and metabolic disorders in gill of genetically improved farmed tilapia (GIFT, Oreochromis niloticus).

The survival and growth of fish are significantly impacted by a hypoxic environment (low dissolved oxygen). In this study, we compared tissue structure, physiological changes, and mRNA/miRNA transcriptome, in gills of genetically improved farmed tilapia (GIFT, Oreochromis niloticus) between the hypoxic group (DO: 0.55 mg/L, HG) and the control group (DO: 5 mg/L, CG). The results showed that the gill filaments in the hypoxic group showed curling, engorgement, and apoptotic cells increased, and that exposure for 96 h resulted in a reduction in the antioxidant capacity. We constructed and sequenced miRNA and mRNA libraries from gill tissues of GIFT at 96 h of hypoxia stress. Between the HG and CG, a total of 14 differentially expressed (DE) miRNAs and 1557 DE genes were obtained. GO and KEGG enrichment showed that DE genes were mainly enriched in immune and metabolic pathways such as natural killer cell mediated cytotoxicity, steroid biosynthesis, primary immunodeficiency, and synthesis and degradation of ketone bodies. Based on the results of mRNA sequencing and screening for miRNA-mRNA pairs, we selected and verified six DE miRNAs and their probable target genes. The sequencing results were consistent with the qRT-PCR validation results. The result showed that under hypoxia stress, the innate immune response was up-regulated, and the adaptive immune response was down-regulated in the gill of GIFT. The synthesis of cholesterol in gill cells is reduced, which is conducive to the absorption of solvent oxygen. These findings offer fresh information about the processes of fish adaptation to hypoxic stress.

Decoding the phonon transport of structural lubrication at silicon/silicon interface.

Although the friction characteristics under different contact conditions have been extensively studied, the mechanism of phonon transport at the structural lubrication interface is not extremely clear. In this paper, we firstly promulgate that there is a 90°-symmetry of friction force depending on rotation angle at Si/Si interface, which is independent of normal load and temperature. It is further found that the interfacial temperature difference under incommensurate contacts is much larger than that in commensurate cases, which can be attributed to the larger interfacial thermal resistance (ITR). The lower ITR brings greater energy dissipation in commensurate sliding, and the reason for that is more effective energy dissipation channels between the friction surfaces, making it easier for the excited phonons at the washboard frequency and its harmonics to transfer through the interface. Nevertheless, the vibrational frequencies of the interfacial atoms between the tip and substrate during the friction process do not match in incommensurate cases, and there is no effective energy transfer channel, thus presenting the higher ITR and lower friction. Eventually, the number of excited phonons on contact surfaces reveals the amount of frictional energy dissipation in different contact states.

Crocetin confers neuroprotection and is anti-inflammatory in rats with induced glaucoma.

BACKGROUND: Crocetin is a bioactive ingredient in saffron, derived from the Crocus sativus stigmas of the Iridaceae family. As a chemically carotenoid derivative, crocetin exhibites effects like anti-inflammatory, antioxidant, neuroprotective, etc. However, the protective effect of crocetin on glaucoma and its mechanism remains unclear. The current study assesed the neuroprotective and anti-inflammatory effects of crocetin on retinal neurons in glaucoma rats which were induced by 0.3% carbomer injection into the anterior chamber. METHODS AND RESULTS: The pathological structures on the retina and optic nerve were observed and examined by H&E staining and transmission electron microscopy. Immunohistochemical staining was used to detect the expression of TNF-α, IL-1ß, and IL-6 of the retina and the expression of a brain-derived neurotrophic factor (BDNF) in the primary visual cortex (PVC). Western blot was carried out to detect the expression of PI3K, Akt, and NF-κB in the retina. It was found that crocetin ameliorated the pathological changes of the retina and ON and reduced the number of apoptotic retinal ganglion cells. Immunohistochemical staining showed that crocetin could decrease the contents of TNF-α, IL-1ß, and IL-6 and increase the contents of BDNF. Western blot showed that crocetin was found to suppress the expression of PI3K, Akt, and NF-κB. CONCLUSION: The results obtained in this study have indicated that crocetin showes neuroprotective effects on retinal ganglion cells in glaucoma rats and inhibits retinal dysfunction. Meanwhile, crocetin exerted an anti-inflammatory effect to protect the retina by inhibiting the expression of the PI3K/Akt/NF-κB signaling pathway. This work provides substantial evidence that crocetin may be a potential drug for the treatment of glaucoma.