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Abstract Crizotinib carries an FDA hepatotoxicity warning, yet analysis of the FAERS database suggests that the severity of its hepatotoxicity risks, including progression to hepatitis and liver failure, might be underreported. However, the underlying mechanism remains poorly understood, and effective intervention strategies are lacking. Here, mRNA-sequencing analysis, along with KEGG and GO analyses, revealed that DEGs linked to Crizotinib-induced hepatotoxicity predominantly associate with the ferroptosis pathway which was identified as the principal mechanism behind Crizotinib-induced hepatocyte death. Furthermore, we found that ferroptosis inhibitors, namely Ferrostatin-1 and Deferoxamine mesylate, significantly reduced Crizotinib-induced hepatotoxicity and ferroptosis in both in vivo and in vitro settings. We have also discovered that overexpression of AAV8-mediated Nrf2 could mitigate Crizotinib-induced hepatotoxicity and ferroptosis in vivo by restoring the imbalance in glutathione metabolism, iron homeostasis, and lipid peroxidation. Additionally, both Stat1 deficiency and the Stat1 inhibitor NSC118218 were found to reduce Crizotinib-induced ferroptosis. Mechanistically, Crizotinib induces the phosphorylation of Stat1 at Ser727 but not Tyr701, promoting the transcriptional inhibition of Nrf2 expression after its entry into the nucleus to promote ferroptosis. Meanwhile, we found that MgIG and GA protected against hepatotoxicity to counteract ferroptosis without affecting or compromising the anti-cancer activity of Crizotinib, with a mechanism potentially related to the Stat1/Nrf2 pathway. Overall, our findings identify that the phosphorylation activation of Stat1 Ser727, rather than Tyr701, promotes ferroptosis through transcriptional inhibition of Nrf2, and highlight MgIG and GA as potential therapeutic approaches to enhance the safety of Crizotinib-based cancer therapy.

Electricity is the lifeblood of modern society. However, the predominant source of electricity generation still relies on non-renewable fossil fuels, whose combustion releases greenhouse gases contributing to global warming. The increasing demand for energy and escalating environmental concerns necessitate proactive measures to develop innovative green energy technologies capable of both cooling the Earth and generating electricity. Here, we look forward to an interdisciplinary power system integrating solar absorbers, radiative coolers, and thermoelectric generators. This system can simultaneously harvest thermal energy from the sun and from cold space, thereby transforming the challenges posed by global warming into opportunities for the production of clean electricity. We underscore recent advancements in this field and address key challenges while also exploring forward-looking opportunities in the foreseeable future. The proposed integrated energy technology achieves uninterrupted power supply through the unrestricted capture of thermal energy, offering a robust alternative pathway for next-generation sustainable energy technologies.

Liver disease has emerged as a significant worldwide health challenge due to its diverse causative factors and therapeutic complexities. The majority of liver diseases ultimately progress to end-stage liver disease and liver transplantation remains the only effective therapy with the limitations of donor organ shortage, lifelong immunosuppressants and expensive treatment costs. Numerous pre-clinical studies have revealed that extracellular vesicles released by mesenchymal stem cells (MSC-EV) exhibited considerable potential in treating liver diseases. Although natural MSC-EV has many potential advantages, some characteristics of MSC-EV, such as heterogeneity, uneven therapeutic effect, and rapid clearance in vivo constrain its clinical translation. In recent years, researchers have explored plenty of ways to improve the therapeutic efficacy and rotation rate of MSC-EV in the treatment of liver disease. In this review, we summarized current strategies to enhance the therapeutic potency of MSC-EV, mainly including optimization culture conditions in MSC or modifications of MSC-EV, aiming to facilitate the development and clinical application of MSC-EV in treating liver disease.

One of the key properties of the kinetic energy penetrator is self-sharpening ability during penetration. In this work, twisted tungsten-fiber-reinforced Cu–Zn composites with varying volume fraction of twisting fibers are designed to optimize self-sharpening capacity. The high-strain-rate compression and penetration behavior of the composites are systematically investigated. It was shown that the penetrator made of partially twisted-tungsten -fiber has the best penetration properties, which is marked by a 57% increased penetration depth compared with the untwisted penetrator. This is attributed to the excellent self-sharpening capability, rendering the head of remnant acute. The self-sharpening capability of the partially-twisted composite originates from the mismatch of the mechanical behavior between the edge and center part of the material. In specific, the tungsten fibers of the edge part are prone to fracture under shear deformation. The different macro-structure and microstructure between center and edge of the composite is favored for excellent penetration performance.

Multidrug-resistant (MDR) bacteria pose a significant clinical threat to human health, but the development of antibiotics cannot meet the urgent need for effective agents, especially those that can kill persisters and biofilms. Here, we reported that nigericin showed potent bactericidal activity against various clinical MDR Gram-positive bacteria, persisters and biofilms, with low frequencies of resistance development. Moreover, nigericin exhibited favorable in vivo efficacy in deep-seated mouse biofilm, murine skin and bloodstream infection models. With Staphylococcus aureus, nigericin disrupted ATP production and electron transport chain; cell death was associated with altered membrane structure and permeability. Obtaining nigericin-resistant/tolerant mutants required multiple rounds of challenge, and, cross-resistance to members of several antimicrobial classes was absent, probably due to distinct nigericin action with the GraSR two-component regulatory system. Thus, our work reveals that nigericin is a promising antibiotic candidate for the treatment of chronic or recurrent infections caused by Gram-positive bacteria.

A rigid polyurethane foam (RPUF) composite was prepared by compounding phytic acid (PA)-functionalized Graphite oxide (PA-GO) with flame-retardant poly (Ammonium phosphate) (APP) and expandable graphite (EG). The effects of PA-GO on the thermal, flame-retardant, and mechanical properties of RPUF were studied using a thermogravimetric analyzer, a limiting oxygen index (LOI) tester, a UL-94 vertical combustion tester, a cone calorimeter, scanning electron microscopy, and a universal tensile testing machine. The results indicated that there was a significant synergistic flame-retardant effect between PA-GO and the intumescent flame retardants (IFR) in the RPUF matrix. Compared with RPUF-1, the addition of 0.3 wt% PA-GO could increase LOI from 25.7% to 26.5%, increase UL-94 rating from V-2 to V-0, and reduce the peak heat release rate (PHRR) and total heat release rate (THR) by 28.5% and 22.2%, respectively. Moreover, the amount of residual char increased from 22.2 wt% to 24.6 wt%, and the char layer was continuous and dense, with almost no holes. Meanwhile, the loss of mechanical properties was apparently lightened.

Summary: There is an urgent need for alternative compact technologies that can derive and store energy from the sun, especially the large amount of solar heat that is not effectively used for power generation. Here, we report a combination of solution- and neat-film-based molecular solar thermal (MOST) systems, where solar energy can be stored as chemical energy and released as heat, with microfabricated thermoelectric generators to produce electricity when solar radiation is not available. The photophysical properties of two MOST couples are characterized both in liquid with a catalytical cycling setup and in a phase-interconvertible neat film. Their suitable photophysical properties let us combine them individually with a microelectromechanical ultrathin thermoelectric chip to use the stored solar energy for electrical power generation. The generator can produce, as a proof of concept, a power output of up to 0.1 nW (power output per unit volume up to 1.3 W m−3). Our results demonstrate that such a molecular thermal power generation system has a high potential to store and transfer solar power into electricity and is thus potentially independent of geographical restrictions.

Abstract Multilayer structure is one of the research focuses of thermoelectric (TE) material in recent years. In this work, n-type 800 nm Bi2Te3/(Pt, Au) multilayers are designed with p-type Sb2Te3 legs to fabricate ultrathin microelectromechanical systems (MEMS) TE devices. The power factor of the annealed Bi2Te3/Pt multilayer reaches 46.5 μW cm−1 K−2 at 303 K, which corresponds to more than a 350% enhancement when compared to pristine Bi2Te3. The annealed Bi2Te3/Au multilayers have a lower power factor than pristine Bi2Te3. The power of the device with Sb2Te3 and Bi2Te3/Pt multilayers measures 20.9 nW at 463 K and the calculated maximum output power reaches 10.5 nW, which is 39.5% higher than the device based on Sb2Te3 and Bi2Te3, and 96.7% higher than the Sb2Te3 and Bi2Te3/Au multilayers one. This work can provide an opportunity to improve TE properties by using multilayer structures and novel ultrathin MEMS TE devices in a wide variety of applications.

Abstract Combustion is a chemical reaction that emits heat and light. Nanofire is a kind of flameless combustion that occurs on the micro–nano scale. Pt/Al2O3 film with a thickness of 20 nm can be prepared as a catalyst by micro–nano processing. When the methanol-air mixture gas passes through the surface of the catalyst, a chemical reaction begins and a significant temperature rise occurs in the catalyst region. Compared to macroscopic combustion, Nanofire has many special properties, such as large temperature gradients, uniform temperature distribution, and fast temperature response. The large temperature gradient is the most important property of Nanofire, which can reach 1330 K/mm. Combined with thermoelectric materials, it can realize the efficient conversion of chemical energy to electric energy. Nanoscale thickness offers the possibility of establishing thermal gradient. On the other hand, large thermal gradient has an effect on the transport properties of phonons and electrons in film materials. From these we can get the scale effects of heat. This article will provide an overview of the preparation, properties and applications of Nanofire, and then a comprehensive introduction to the thermal scale and thermal scale effects.

Photothermal conversion is an environmentally friendly process that harvests energy from the sun and has been attracting growing research interest in recent years. However, nanostructured strategies to improve light capture performance deserve further development, and the application of solar heating effects for clean energy needs to be explored. Herein, a multiscale nanomaterial was prepared by in situ polymerizing the polyaniline (PANI) nanoparticles into porous anodic aluminum oxide (AAO) membrane. As a result, the as-prepared PANI-AAO shows broadband solar absorption and provides a platform for efficient photothermal conversion. What is more, we introduced a typical thermoelectricity generator (TEG) with excellent output performance and combined it with PANI-AAO to prepare a solar thermoelectric generator (s-TEG). The s-TEG harvests solar energy and converts it into electricity, showing an outstanding power generation capability in outdoor conditions. Thus, the nanostructured broadband solar absorber and the integrated solar thermoelectric generator offer a promising candidate for a sustainable and green energy source in the future.

Abstract Thermoelectric multilayer thin films used in nanoscale energy conversion have been receiving increasing attention in both academic research and industrial applications. Thermal transport across multilayer interface plays a key role in improving thermoelectric conversion efficiency. In this study, the cross-plane thermal conductivities of nano-constructed Sb2Te3/(Cu, Ag, Au, Pt) thermoelectric multilayer thin films have been measured using time-domain thermoreflectance method. The interface morphology features of multilayer thin film samples were characterized by using scanning and transmission electron microscopes. The effects of interface microstructure on the cross-plane thermal conductivities of the multilayer thin films have been extensively examined and the thermal transfer mechanism has been explored. The results indicated that electron–phonon coupling occurred at the semiconductor/metal interface that strongly affected the cross-plane thermal conductivity. By appropriately optimizing the period thickness of the metal layer, the cross-plane thermal conductivity can be effectively reduced, thereby improving the thermoelectric conversion efficiency. This work presents both experimental and theoretical understanding of the thermal transport properties of Sb2Te3/metal multilayer thin film junctions with important implications for exploring a novel approach to improving the thermoelectric conversion efficiency.

Eight new cytochalasins 1–8 and ten known analogs 9–18 were isolated from the endophytic fungus Phomopsis sp. xz-18. The planar structures of the cytochalasins were determined by HR-ESI-MS and NMR analysis. Compounds 1, 2, 9 and 10 were 5/6/6/7/5-fused pentacyclic cytochalasins; compounds 3 and 4 had conjugated diene structures in the macrocycle; and compound 6 had a β,γ-unsaturated ketone. The absolute configuration of 6 was confirmed for the first time by the octant rule. The acid-free purification process proved that the pentacyclic system was a natural biosynthetic product and not an acid-mediated intramolecular cyclized artifact. The new compounds did not exhibit activities against human cancer cell lines in cytotoxicity bioassays or antipathogenic fungal activity, but compounds 1, 3 and 4 showed moderate antibacterial activity in disk diffusion assays.

The interface affects the transmission behavior of electrons and phonons, which in turn determines the performance of thermoelectric materials. In this paper, metals (Cu, Ag, Au)/Al2O3/Bi2Te3 heterostructures have been fabricated from bottom to up to optimize the thermoelectric power factor. The introducing metals can be alloyed with Bi2Te3 or form interstitials or dopants to adjust the carrier concentration and mobility. In addition, the metal-semiconductor interface as well as the metal-insulator-semiconductor interface constructed by the introduced metal and Al2O3 would further participate in the regulation of the carrier transport process. By adjusting the metal and oxide layer, it is possible to realize the simultaneous optimization of electric conductivity and Seebeck coefficient. This work will enable the optimal and novel design of heterostructures for thermoelectric materials with further improved performance.

In this paper, metals’ (Cu, Ag, Au)/Al2O3/Bi2Te3 heterostructures have been fabricated to synergistically optimize their carrier concentration and mobility, thereby enhancing their thermoelectric power factor. Metal can be alloyed with Bi2Te3 to reduce the electron concentration. The introduction of the oxide layer further reduces the electron concentration and leads to an increase in mobility. By adjusting the metal and oxide layer, it is possible to realize the simultaneous optimization of electric conductivity and the Seebeck coefficient. This work will enable the optimal and novel design of heterstructures for thermoelectric materials with further improved performance.

The knowledge of interfacial phonon transport accounting for detailed phonon spectral properties is desired because of its importance for design of nanoscale energy systems. In this work, we investigate the interfacial phonon transport through Si/Ge multilayer films using an efficient Monte Carlo scheme with spectral transmissivity, which is validated for cross-plane phonon transport through both Si/Ge single-layer and Si/Ge bi-layer thin films by comparing with the discrete-ordinates solution. Different thermal boundary conductances between even the same material pair are declared at different interfaces within the multilayer system. Furthermore, the thermal boundary conductances at different interfaces show different trends with varying total system size, with the variation slope, very different as well. The results are much different from those in the bi-layer thin film or periodic superlattice. These unusual behaviors can be attributed to the combined interfacial local non-equilibrium effect and constraint effect from other interfaces.

Aramid fibers (AFs) are widely applied as structural material, cordage, and versatile protection in many harsh environments, including space and deep sea. However, intense ultraviolet (UV)/ irradiation, high/low temperatures, and/or chemical solvent with strong acid/alkali/corrosion feature seriously affect their mechanical properties, thus severely shorten the life cycle of AF-based products. Inspiration by the principle of multiple refractions and partly reflections, an innovative strategy by depositing of laminated Al2O3/TiO2 composite onto the surface of poly(m-phenylene isophthalamide) (PMIA) via atomic layer deposition (ALD) technique was presented. The tenacity of ALD-coated PMIA only decreases by ∼ 8 %, and the yellowness index (YI) only increasing to 129.24 %, far lower than 321.63 % of pristine PMIA fabric under the combination of intense UV irradiation (4260 W/m2) and high temperature (200 °C + ) for 6 h, which equals to continuous strong sunlight exposure for approximately 7.5 years. Meanwhile, ultraviolet protection factor (UPF) value increased to 126.4, which is double that of the pristine PMIA fabric, exhibiting an impressive UV-resistance property. Furthermore, the ALD-coated PMIAs also shows a significant enhancement in both chemical and thermal stabilities. In all, this work not only forge a new route for the functionalization of fibrous materials, but also exhibits great promise for next generation advanced composite material and cutting-edge equipment in harsh environment.

To investigate the effects of administering fermented milk with live Bifidobacterium lactis Y6 on intestinal health in people with digestive dysfunction, a dietary intervention experiment was conducted. Volunteers with digestive problems were selected to consume 200 mL Y6 fermented milk daily for 4 weeks. Clinical scores were performed before and after the intervention, the Illumina PE300 sequencing platform was used to perform high-throughput sequencing of 16S rDNA PCR product fragments of fecal microorganisms in volunteers, the content of short-chain fatty acids (SCFAs) in feces was determined using gas chromatography. The results showed that drinking Y6 fermented milk had a significant improvement on clinical symptoms caused by digestive dysfunction (P

Abstract Background Patients with non‐small‐cell lung cancer (NSCLC) and uncommon EGFR alterations typically have worse treatment outcomes than patients with classically EGFR‐mutated NSCLC. This study aimed to investigate the efficacy and safety of PD‐1 blockade with sintilimab plus anti‐angiogenic treatment with anlotinib in patients with NSCLC harboring uncommon EGFR mutations. Methods Patients with metastatic NSCLC harboring uncommon EGFR mutations after two previous treatments, including a platinum‐based chemotherapy regimen and a targeted treatment (or chemotherapy only for patients harboring EGFR ex20ins), received sintilimab combined with anlotinib. The primary endpoint was objective response rate (ORR). Results At data cutoff (September 27, 2022), median follow‐up was 22.3 months (range, 1.2–37.6). Among 21 enrolled patients, 12 had EGFR ex20ins and nine had other uncommon EGFR mutations such as L861Q, G719A, and G709X. Overall, eight patients (38.1%) achieved an objective response, and 18 (85.7%) achieved disease control. Median (95% CI) progression‐free survival (PFS) was 7.0 (5.4–8.6) months, and median overall survival (OS) was 20.0 (15.6–24.4) months. The 12‐month PFS rate (95% CI) was 22.2% (7.4–42.0), and the 12‐month OS rate was 66.7% (42.5–82.5). Patients harboring EGFR ex20ins had similar ORR and PFS to those with other mutations. Six patients (28.6%) experienced grade 3 treatment‐related adverse events (TRAEs); hand‐foot syndrome was the most common grade 3 TRAE (2 patients; 9.5%). No grade ≥4 TRAEs were observed. Conclusions The combination of sintilimab and anlotinib demonstrated durable efficacy and was generally well tolerated in patients with NSCLC and uncommon EGFR mutations who had received prior standard‐of‐care treatments. (ClinicalTrials.gov identifier: NCT04790409).

To address the difficulty of detecting low embedding rate and high-concealment CNV-QIM (complementary neighbor vertices-quantization index modulation) steganography in low bit-rate speech codec, the code-word correlation model based on a BiLSTM (bi-directional long short-term memory) neural network is built to obtain the correlation features of the LPC codewords in speech codec in this paper. Then, softmax is used to classify and effectively detect low embedding rate CNV-QIM steganography in VoIP streams. The experimental results show that for speech steganography of short samples with low embedding rate, the BiLSTM method in this paper has a superior detection accuracy than state-of-the-art methods of the RNN-SM(recurrent neural network-steganalysis model) and SS-QCCN (simplest strong quantization codeword correlation network). At an embedding rate of 20% and a duration of 3 s, the detection accuracy of BiLSTM method reaches 75.7%, which is higher than that of RNNSM by 11.7%. Furthermore, the average testing time of samples (100% embedding) is 0.3 s, which shows that the method can realize real-time steganography detection of VoIP streams. [ABSTRACT FROM AUTHOR]

Highly (001)-textured antimony telluride films were fabricated using molecular beam epitaxy (MBE) on Si (111) substrate at 280 °C. X-ray diffraction analysis implying the samples have good crystalline quality, simultaneously, the grain sizes coarsening with increasing thickness. The results of Hall coefficient measurement demonstrated that the carrier concentration and mobility are strongly affected by grain boundaries and microcrystalline internal defects. It was found that the grain boundaries play a primary factor influencing the carrier concentration in thinner film. At room temperature, the results in a maximum mobility value of 305 cm²=Vs for 121-nm-thick film, and the electrical conductivity increased from 425.7 S/cm to 1036 S/cm as the thickness varied from 28 nm to 121 nm. In the range of room temperature to 150 °C, the resistivity almost linearly increased with increasing temperature. This may be explained by low concentration of impurities or defects and shallow impurity band. For difference thickness films, temperature coefficients of resistivity are substantially equal, and the values are about 3~4 µΩ ⋅ cm=K. [ABSTRACT FROM AUTHOR]

BackgroundQL1604 is a humanized immunoglobulin G4 monoclonal antibody against programmed cell death protein 1. This first-in-human, open-label phase I study aimed to investigate the safety and tolerability and to identify the recommended doses of QL1604 for future studies. Pharmacokinetics/pharmacodynamics (PK/PD) and preliminary antitumor activity were also assessed.MethodsPatients with advanced or metastatic solid tumors who failed or had no standard therapies available were recruited. In the dose-escalation phase, patients were treated with QL1604 at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg intravenously once every 2 weeks (Q2W) in an accelerated titration with a traditional 3 + 3 design, followed by a dose-expansion phase at 3 mg/kg Q2W, 3 mg/kg once every 3 weeks (Q3W), 10 mg/kg Q2W and a fixed dose of 200 mg Q3W. Dose-limiting toxicities (DLTs) were assessed during the first 28 days after the first dose of study drug. Adverse events (AEs) were graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0, and antitumor activity of QL1604 was evaluated by investigators on the basis of Response Evaluation Criteria in Solid Tumors version 1.1.ResultsA total of 35 patients with advanced or metastatic solid tumors were enrolled. DLTs were reported in one patient at the dose level of 3 mg/kg Q2W (grade 3 immune-mediated myositis and myasthenia gravis), and maximum tolerated dose was not reached. The most frequent treatment-related AEs (≥10%) were fatigue (37.1%), anemia (22.9%), increased blood thyroid-stimulating hormone (17.1%), increased aspartate aminotransferase (AST) (17.1%), increased alanine aminotransferase (ALT) (14.3%), decreased white blood cell (WBC) count (11.4%), rash (14.3%), and pruritus (14.3%). AEs leading to discontinuation of QL1604 occurred in three of the 35 patients (8.6%). Partial responses (PRs) occurred in seven patients, resulting in an objective response rate of 20.0% (7/35). Single dose of QL1604 exhibited a dose-dependent increase in the exposure ranging from 0.3 mg/kg to 10 mg/kg. Mean receptor occupancy (RO) for QL1604 at the dose of 3 mg/kg (Q2W and Q3W) and 200 mg (Q3W) was greater than 80% during cycle 1 after one infusion.ConclusionQL1604 monotherapy exhibited favorable safety, PK, and signal of antitumor activity in patients with advanced or metastatic solid tumors, and the results supported further clinical studies of QL1604. On the basis of the safety, PK, and RO data, the recommended dosage for further clinical trials is 3 mg/kg or a fixed dose of 200 mg given every 3 weeks.Clinical Trial Registrationhttps://classic.clinicaltrials.gov/ct2/show/NCT05649761?term=QL1604&draw=2&rank=1, identifier NCT05649761.

Due to its limited intelligence and abilities, machine learning is currently unable to handle various situations thus cannot completely replace humans in real-world applications. Because humans exhibit robustness and adaptability in complex scenarios, it is crucial to introduce humans into the training loop of artificial intelligence (AI), leveraging human intelligence to further advance machine learning algorithms. In this study, a real-time human-guidance-based (Hug)-deep reinforcement learning (DRL) method is developed for policy training in an end-to-end autonomous driving case. With our newly designed mechanism for control transfer between humans and automation, humans are able to intervene and correct the agent’s unreasonable actions in real time when necessary during the model training process. Based on this human-in-the-loop guidance mechanism, an improved actor-critic architecture with modified policy and value networks is developed. The fast convergence of the proposed Hug-DRL allows real-time human guidance actions to be fused into the agent’s training loop, further improving the efficiency and performance of DRL. The developed method is validated by human-in-the-loop experiments with 40 subjects and compared with other state-of-the-art learning approaches. The results suggest that the proposed method can effectively enhance the training efficiency and performance of the DRL algorithm under human guidance without imposing specific requirements on participants’ expertise or experience.

Abstract Previous small-size studies reported BRAF-mutated NSCLC patients have comparable sensitivity to immune checkpoint inhibitors (ICIs). However, how BRAF mutation affects the tumor immune microenvironment (TIME) is unknown. We performed Nanostring-panel RNA sequencing to evaluate TIME in 57 BRAF mutated and wild-type (WT) NSCLC specimens (cohort A). The efficacy of ICI monotherapy or combined therapies was determined in 417 patients with WT and BRAF mutated NSCLC (cohort B). We found that BRAF-mutant tumors had similar ratios of CD8+ T cells to Tregs, the balance of cytotoxicity gene expression signatures and immune suppressive features, and similar ICI-response-related biomarkers to WT NSCLC. A similar TIME pattern was observed between the BRAF V600E and Non-V600E subgroups of NSCLC. The further retrospective study confirmed that treatment with ICI monotherapy or combined therapies resulted in similar overall survival (OS) (HR: 0.85; 95% CI, 0.56 to 1.30; p = 0.47) and progress-free survival (PFS) (HR: 1.02; 95% CI, 0.72 to 1.44; p = 0.91) of patients with WT (n = 358) and BRAF mutant (n = 59) NSCLC. Similarly, both patients with BRAF V600E or Non-V600E NSCLC had similar responses to immunotherapy. Our findings support that BRAF mutation did not modulate TIME in NSCLC and therapeutic responses to ICIs. Patients with NSCLC harboring BRAF mutation should not be denied treatment with ICIs.

An ultraviolet (UV)-protective cotton fabric has been developed by combining tannic acid and copper ions (TA-Cu) on cotton fabrics. The structure and properties of TA-Cu and cotton fabrics finished with TA-Cu were characterized by Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, scanning electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The UV resistance and laundering durability of modified cotton fabrics were measured. The cotton fabric finished with tannic acid showed a maximum UV-protection factor value of 44.5, which was further improved by chelation with copper ions. The cotton fabric finished by the TA-Cu exhibits a UV-protection factor value of up to 172.1 and a UV transmittance of less than 1.5% when the concentration of tannic acid and copper ions was 0.1 mmol/L. The as-prepared cotton fabrics retained their UV resistance after laundering. This study proposes an eco-friendly anti-UV treatment for cotton fabrics and a novel application for tannic acid and copper ions to imbue fabrics with UV protection.

Long non-coding RNAs (lncRNAs) are commonly known for their important characters in cancer progression. LncRNA MAFG-antisense 1 (AS1) (MAFG-AS1) has been discovered as a novel oncogenic lncRNA for several years. Accumulating data have demonstrated abnormal overexpression of MAFG-AS1 in various human cancers, including breast, bladder, liver, gastric, and lung. Importantly, through regulating various microRNAs and cell signaling pathways, MAFG-AS1 has been demonstrated to exhibit various biological effects, including proliferation, metastasis, and epithelial-mesenchymal transition (EMT). Meanwhile, abnormal overexpression of MAFG-AS1 is closely linked with histological grade, TNM stage, extensive depth of invasion, poor OS, and lymph node metastasis (LNM). In the present review, the authors summarized the previous studies on the biological properties, molecular mechanisms, and clinicopathological characters of MAFG-AS1 in human cancers. In summary, MAFG-AS1 is a promising prognostic biological marker and potential therapeutic target for cancer treatment.

BackgroundThe circulating predictive factors for the outcomes of advanced non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs) remain elusive. We aimed to assess the predictive value of circulating cytokines for outcomes.MethodsSerum samples of 102 advanced-stage NSCLC patients who underwent immunotherapy were collected at baseline. The relative levels of 37 cytokines were detected. PD-L1 expression was also analyzed.ResultsHigher serum CXCL12 levels (top 33%) were a poor predictive biomarker for durable clinical benefit (DCB) (23.5% vs. 72.1%, p

In order to understand the current situation and measures of physical training of volleyball team in higher vocational colleges, this paper takes the current situation of physical training of volleyball team in Higher Vocational Colleges as the object, starting with the physical training of volleyball team in Higher Vocational Colleges as the starting point, using the methods of literature review, questionnaire survey, expert interview and mathematical statistics, briefly discusses the concept of physical training of volleyball team in Higher Vocational Colleges at this stage, and analyzes the current stage of vocational colleges This paper analyzes the performance of insufficient physical training of college volleyball team, and introduces the new concept of physical training to analyze the optimization measures of physical training of volleyball team in higher vocational colleges. It is concluded that the basic situation of volleyball players in higher vocational colleges is not different, which has no great impact on physical training, but the physical training lacks certain scientificity, and the training mode is relatively single, and the training plan is not targeted. Through scientific physical training, we can improve the competitive ability of volleyball players in higher vocational colleges. Therefore, physical fitness is an important component of the competitive ability of volleyball players in higher vocational colleges, and good physical quality is the key for volleyball players in Higher Vocational Colleges to have high-level technology and obtain good sports results.

The phosphoinositide 3-kinase (PI3K) signaling pathway is well-known for its important role in cancer growth, proliferation and migration. The activation of PI3K pathway is always connected with endocrine resistance and poor prognosis in cancers. Alpelisib, a selective inhibitor of PI3K, has been demonstrated to be effective in combination with endocrine therapy in HR+ PIK3CA-mutated advanced breast cancer in preclinical and clinical trials. Recently, the synergistic effects of alpelisib combined with targeted agents have been widely reported in PIK3CA-mutated cancer cells, such as breast, head and neck squamous cell carcinoma (HNSCC), cervical, liver, pancreatic and lung cancer. However, previous reviews mainly focused on the pharmacological activities of alpelisib in breast cancer. The synergistic therapeutic potential of alpelisib in other cancers has not yet been well reviewed. In this review, an extensive study of related literatures (published until December 20, 2022) regarding the anti-cancer functions and synergistic effects of alpelisib was carried out through the databases. Useful information was extracted. We summarized the preclinical and clinical studies of alpelisib in combination with targeted anti-cancer agents in cancer treatment (excluding breast cancer). The combinations of alpelisib and other targeted agents significantly improved the therapeutic efficacy both in preclinical and clinical studies. Unfortunately, synergistic therapies still could not effectively avoid the possible toxicities and adverse events during treatment. Finally, some prospects for the combination studies in cancer treatment were provided in the paper. Taken together, this review provided valuable information for alpelisib in preclinical and clinical applications.

Abstract Background Determining the tissue of origin (TOO) is essential for managing cancer of unknown primary (CUP). In this study, we evaluated the concordance between genome profiling and DNA methylation analysis in determining TOO for lung-specific CUP and assessed their performance by comparing the clinical responses and survival outcomes of patients predicted with multiple primary or with metastatic cancer. Methods We started by retrospectively screening for CUP patients who presented with both intra- and extrathoracic tumors. Tumor samples from included patients were analyzed with targeted sequencing with a 520-gene panel and targeted bisulfite sequencing. TOO inferences were made in parallel via an algorithm using genome profiles and time interval between tumors and via machine learning-based classification of DNA methylation profiles. Results Four hundred patients were screened retrospectively. Excluding patients definitively diagnosed with conventional diagnostic work-up or without available samples, 16 CUP patients were included. Both molecular approaches alone enabled inference of clonality for all analyzed patients. Genome profile enabled TOO inference for 43.8% (7/16) patients, and the percentage rose to 68.8% (11/16) after considering inter-tumor time lag. On the other hand, DNA methylation analysis was conclusive for TOO prediction for 100% (14/14) patients with available samples. The two approaches gave 100% (9/9) concordant inferences regarding clonality and TOO identity. Moreover, patients predicted with metastatic disease showed significantly shorter overall survival than those with multiple primary tumors. Conclusions Genome and DNA methylation profiling have shown promise as individual analysis for TOO identification. This study demonstrated the feasibility of incorporating the two methods and proposes an integrative scheme to facilitate diagnosing and treating lung-specific CUPs.

Abstract Accumulating evidence indicates that inflammation and nutrition status are associated with clinical outcomes in patients with various malignancies. This study aimed to evaluate the prognostic significance of the pretreatment platelet to albumin ratio (PAR) in esophageal squamous cell carcinoma (ESCC) patients undergoing definitive radiotherapy. A total of 470 patients who underwent definitive radiotherapy with or without chemotherapy were enrolled. The optimal cut-off values of PAR and other indicators were determined by the X-tile. The Kaplan–Meier method, multivariate analyses Cox regression were conducted to identify the association between those indicators and the survival outcomes. The median follow-up time was 23.5 months. The optimal cut-off value of PAR was 5.7 × 109 and patients were stratified as the low PAR group and the high PAR group. In the univariate analysis, a low overall survival rate was significantly associated with T stage (P = 0.005), TNM stage (P

Abstract Bone morphogenetic protein 1 (BMP1) belongs to the astacin/BMP1/tolloid-like family of zinc metalloproteinases, which play a fundamental role in the development and formation of extracellular matrix (ECM). BMP1 mediates the cleavage of carboxyl terminal (C-term) propeptides from procollagens, a crucial step in fibrillar collagen fiber formation. Blocking BMP1 by small molecule or antibody inhibitors has been linked to anti-fibrotic activity in the preclinical models of skin, kidney and liver fibrosis. Therefore, we reason that BMP1 may be important for the pathogenesis of lung fibrosis and BMP1 could be a potential therapeutic target for progressive fibrotic disease such as idiopathic pulmonary fibrosis (IPF). Here, we observed the increased expression of BMP1 in both human IPF lungs and mouse fibrotic lungs induced by bleomycin. Furthermore, we developed an inducible Bmp1 conditional knockout (cKO) mouse strain. We found that Bmp1 deletion does not protect mice from lung fibrosis triggered by bleomycin. Moreover, we found no significant impact of BMP1 deficiency upon C-term propeptide of type I procollagen (CICP) production in the fibrotic mouse lungs. Based on these results, we propose that BMP1 is not required for lung fibrosis in mice and BMP1 may not be considered a candidate therapeutic target for IPF.

Abstract Background Brain metastasis is a common and lethal complication of non-small cell lung cancer (NSCLC). It is mostly diagnosed only after symptoms develop, at which point very few treatment options are available. Therefore, patients who have an increased risk of developing brain metastasis need to be identified early. Our study aimed to identify genomic and epigenomic biomarkers for predicting brain metastasis risk in NSCLC patients. Methods Paired primary lung tumor tissues and either brain metastatic tissues or cerebrospinal fluid (CSF) samples were collected from 29 patients with treatment-naïve advanced NSCLC with central nervous system (CNS) metastases. A control group comprising 31 patients with advanced NSCLC who died without ever developing CNS metastasis was also included. Somatic mutations and DNA methylation levels were examined through capture-based targeted sequencing with a 520-gene panel and targeted bisulfite sequencing with an 80,672 CpG panel. Results Compared to primary lung lesions, brain metastatic tissues harbored numerous unique copy number variations. The tumor mutational burden was comparable between brain metastatic tissue (P = 0.168)/CSF (P = 0.445) and their paired primary lung tumor samples. Kelch-like ECH-associated protein (KEAP1) mutations were detected in primary lung tumor and brain metastatic tissue samples of patients with brain metastasis. KEAP1 mutation rate was significantly higher in patients with brain metastasis than those without (P = 0.031). DNA methylation analysis revealed 15 differentially methylated blocks between primary lung tumors of patients with and without CNS metastasis. A brain metastasis risk prediction model based on these 15 differentially methylated blocks had an area under the curve of 0.94, with 87.1% sensitivity and 82.8% specificity. Conclusions Our analyses revealed 15 differentially methylated blocks in primary lung tumor tissues, which can differentiate patients with and without CNS metastasis. These differentially methylated blocks may serve as predictive biomarkers for the risk of developing CNS metastasis in NSCLC. Additional larger studies are needed to validate the predictive value of these markers.

The heterogeneous Fenton system has drawn great attention in recent years due to its effective degradation of polluted water capability without limitation of the pH range and avoiding excess ferric hydroxide sludge. Therefore, simple chemical precipitation and vacuum filtration method for manufacturing the heterogeneous Fenton aramid nanofibers (ANFs)/ferrous oxalate (FeC2O4) composite membrane catalysts with excellent degradation of methylene blue (MB) is reported in the study. The morphology and structure of materials synthesized were characterized by scanning electron microscope (SEM), X-ray energy spectrum analysis (EDS), infrared spectrometer (FTIR), and X-ray diffraction (XRD) equipment. The 10 ppm MB degradation efficiency of composite catalyst and ferrous oxalate (FeC2O4) within 15 min were 94.5% and 91.6%, respectively. The content of methylene blue was measured by a UV-Vis spectrophotometer. Moreover, the dye degradation efficiency still could achieve 92% after five cycles, indicating the composite catalyst with excellent chemical stability and reusability. Simultaneously, the composite catalyst membrane can degrade not only MB but also rhodamine B (RB), orange II (O II), and methyl orange (MO). This study represents a new avenue for the fabrication of heterogeneous Fenton catalysts and will contribute to dye wastewater purification, especially in the degradation of methylene blue.

Herein, a comprehensive examination of the effect of concentration on graphene oxide (GO) photoluminescence (PL) is presented. It is found that GO exhibits a concentration‐induced redshift and white light PL for GO aqueous dispersions, and displays visible–NIR PL for a 3D GO foam (3DGOF) corresponding to the high‐concentration‐limit of GO. It is deduced that the effect of the coupling between the GO sheets gives rise to the observed redshift, and hopping and tunneling effects result in the saturation of the PL redshift and then the PL quenching. Due to the intense interactions and coupling of the GO sheets, the modification of the GO surface state increases the energy of the π* state and/or makes the high‐energy level appear and therefore gives rise to the blue light component. Consequently, high concentrations of GO aqueous dispersion lead to the appearance of combined white light. For 3DGOF, electron–hole radiation recombination in laser‐induced plasma and GO bandgap may be responsible for the observed visible–NIR PL. Based on its tunable PL in the visible–NIR region of the spectrum and the induced white light PL, GO has huge potential for applications in graphene‐based optoelectronics and biomedicine.

BackgroundSmall-cell lung cancer (SCLC) is the most lethal cancer. With the development of chemotherapy and radiotherapy, brain metastasis (BM) emerged as one most predominant treatment failure. However, the factors affecting BM have not been identified completely. The purpose of this study was to investigate the risk factors involved in the development of BM in patients with limited-stage small-cell lung cancer (LS-SCLC) following definitive thoracic radiotherapy (TRT) and to provide a reference for the planning of a clinical treatment strategy.MethodsThe clinical data of patients with LS-SCLC treated with neoadjuvant chemotherapy (NAC) followed by TRT were collected and retrospectively reviewed. The factors affecting BM, BM-free survival (BMFS) and overall survival (OS) rates were analyzed statistically.ResultsA total of 152 patients with LS-SCLC fulfilled the inclusion criteria were reviewed. Following TRT, 31 (20.4%) patients achieved CR, 90 (59.2%) patients reached PR, 31 (20.4%) patients maintained SD, and no patients developed PD. The OS at 1, 3, and 5 years was 80.6, 34.2, and 19.4%, respectively. Multivariate analyses indicated that the greatest dimension of primary tumor (Dmax-T) and short-term response to TRT were risk factors affecting BM. The clinical N stage (cN), greatest dimension of metastatic nodes (Dmax-N), short-term response to TRT, and adjuvant chemotherapy (AC) were identified as independent factors correlated with OS.ConclusionsPoor short-term response to TRT and huger Dmax-T were risk factors for BM. AC following TRT improved patient survival, but not decreased BM. However, due to the limitations associated with the retrospective design of the present study, further prospective clinical trials are required to confirm these conclusions.

Photoacoustic microscopy (PAM) and optical coherence tomography (OCT) are sensitive to optical absorption and scattering characteristics, respectively. As such, the integration of these two modalities in order to combine important complementary information has garnered much attention. Due to the relatively low axial resolution of PAM, PAM and OCT dual modality systems generally have a large resolution gap, especially for reflection mode systems. In this study, based on a wide-band transparent pure-optical ultrasonic detector, we developed a dual modality system (PAM-OCT system) in which PAM has a similar spatial resolution (i.e. several micrometers in both the lateral and axial directions) to OCT. In addition, due to the optical transparency advantage, the integrated system works in reflection mode, which is ideal for in vivo biomedical imaging. We successfully imaged the skin of a mouse hindlimb, which cannot be done by a transmission mode dual modality system. Our work demonstrates this dual modality system has potential in biomedical studies with complementary imaging contrasts.

Background/Aims: Cyclin-dependent kinase 6 (CDK6) regulates inflammatory response and cell differentiation. This study sought to determine whether CDK6 and miR-320c co-regulate chondrogenesis and inflammation. Methods: Utilizing quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), CDK6 and miR-320c expression were assessed in a micromass culture of human bone mesenchymal stem cells that underwent chondrogenesis in vitro as well as in chondrocytes from E16.5 mouse forelimbs. Normal chondrocytes were transfected with miR-320c mimic, miR-320c inhibitor, or CDK6-siRNA. Luciferase reporter assay results confirmed that miR-320c directly targets CDK6 by interacting with the 3′-untranslated region (3′-UTR) of its mRNA. qRT-PCR, Western blotting, and Cell Counting Kit-8 were subsequently used to evaluate the effects of miR-320c overexpression and CDK6 inhibition on inflammatory factor expression, as well as to investigate the effects of NF-kB and MAPK signaling pathway activation on IL-1β-induced chondrocyte inflammation. Results: Our results show that miR-320c expression increased during the middle stage and decreased during the late stage of hBMSC chondrogenic differentiation. In contrast, CDK6 expression decreased during the middle stage and increased during the late stage of hBMSC chondrogenic differentiation. Moreover, CDK6 expression increased in severe OA cartilage and in hypertrophic chondrocytes of mouse forelimbs at E16.5. Results of the luciferase reporter assay showed that miR-320c modulated CDK6 expression by binding to the 3′-UTR of its mRNA. miR-320c overexpression and CDK6 inhibition repressed IL-1β-induced expression of inflammatory factors and regulated the NF-kB signaling pathway. Conclusion: CDK6 and miR-320c co-regulate hBMSC chondrogenesis and IL-1β-induced chondrocyte inflammation through the NF-kB signaling pathway, suggesting that miR-320c and CDK6 inhibitors can be used to repress catabolism in human chondrocytes.

Abstract Background WNT5A is known to be involved in the pathogenesis of osteoarthritis. This study investigated the molecular mechanism of exosomal miR-92a-3p and WNT5A in chondrogenesis and cartilage degeneration. Methods Exosomal miR-92a-3p expression was assessed in vitro in a human mesenchymal stem cell (MSC) model of chondrogenesis and in normal and OA primary human chondrocytes (PHCs). MSCs and PHCs were treated with exosomes derived from MSC-miR-92a-3p (MSC-miR-92a-3p-Exos) or its antisense inhibitor (MSC-anti-miR-92a-3p-Exos), respectively. Small interfering RNAs (siRNAs) and luciferase reporter assay were used to reveal the molecular role of exosomal miR-92a-3p and WNT5A in chondrogenesis. The protective effect of exosomes in vivo was measured using Safranin-O and Fast Green staining and immunohistochemical staining. Results Exosomal miR-92a-3p expression was elevated in the MSC chondrogenic exosome, while it was significantly reduced in the OA chondrocyte-secreted exosome compared with normal cartilage. Treatment with MSC-miR-92a-3p-Exos promoted cartilage proliferation and matrix genes expression in MSCs and PHCs, respectively. In contrast, treatment with MSC-anti-miR-92a-3p-Exos repressed chondrogenic differentiation and reduced cartilage matrix synthesis by enhancing the expression of WNT5A. Luciferase reporter assay demonstrated that miR-92a-3p suppressed the activity of a reporter construct containing the 3’-UTR and inhibited WNT5A expression in both MSCs and PHCs. MSC-miR-92a-3p-Exos inhibit cartilage degradation in the OA mice model. Conclusions Our results suggest that exosomal miR-92a-3p regulates cartilage development and homeostasis by directly targeting WNT5A. This indicates that exosomal miR-92a-3p may act as a Wnt inhibitor and exhibits potential as a disease-modifying osteoarthritis drug.

Abstract Background Fundus fluorescein angiography (FFA) imaging is a standard diagnostic tool for many retinal diseases such as age-related macular degeneration and diabetic retinopathy. High-resolution FFA images facilitate the detection of small lesions such as microaneurysms, and other landmark changes, in the early stages; this can help an ophthalmologist improve a patient’s cure rate. However, only low-resolution images are available in most clinical cases. Super-resolution (SR), which is a method to improve the resolution of an image, has been successfully employed for natural and remote sensing images. To the best of our knowledge, no one has applied SR techniques to FFA imaging so far. Methods In this work, we propose a SR method-based pipeline for FFA imaging. The aim of this pipeline is to enhance the image quality of FFA by using SR techniques. Several SR frameworks including neighborhood embedding, sparsity-based, locally-linear regression and deep learning-based approaches are investigated. Based on a clinical FFA dataset collected from Second Affiliated Hospital to Xuzhou Medical University, each SR method is implemented and evaluated for the pipeline to improve the resolution of FFA images. Results and conclusion As shown in our results, most SR algorithms have a positive impact on the enhancement of FFA images. Super-resolution forests (SRF), a random forest-based SR method has displayed remarkable high effectiveness and outperformed other methods. Hence, SRF should be one potential way to benefit ophthalmologists by obtaining high-resolution FFA images in a clinical setting.

Bi2Te3 thin films were electrodeposited on silicon substrate with a epitaxial seed layer from acidic aqueous solutions at room temperature. The seed layer optimized the charge transfer in the electrodeposition process and reduced the lattice mismatch between the thin film and the substrate, leading to the Bi2Te3 thin films with uniform structure and highly crystallographically texture. By changing the substrate from doped to intrinsic silicon, we obtained the Bi2Te3 thin films with (00L) preferential orientation which is different from previously reported (015) or (110)-oriented thin films prepared by ECD. The (00L)-oriented thin film showed a more compact structure with lower roughness and an improved thermoelectric performance. The electrical conductivity increased by about 72% compared with the (110)-oriented thin film in our system. Simultaneously, the Seebeck coefficient was comparable, indicating the improvement of power factors by ~45%. We also altered the thickness of the seed layer from 40 nm to 20 nm and found that both the electrical conductivity and Seebeck coefficient decreased due to the insufficient charge transfer in the electrodeposition process. [ABSTRACT FROM AUTHOR]

Seven novel polyketides, namely, 1xylarenone Axylariate A 1, xylarioic acid B 2, xylariolide A 3, xylariolide B 4, xylariolide C 5, methyl xylariate C 6, and xylariolide D 7, together with the known one taiwapyrone 8, were isolated from the endophytic fungal strain Xylariasp. NCY2 of Torreya jackiiChun. Their structures were elucidated by spectroscopic analyses, including 1D and 2DNMR experiments, and on the basis of HRQTOF mass spectrometry. Antitumor and antibacterial assays of compounds 1–8were carried out, which show moderate activities. [ABSTRACT FROM AUTHOR]

In this article, various energies and geometries of pure platinum nanoparticles and those of platinum nanoparticles with adsorbed OH were investigated. Fourteen different platinum clusters of 3–40 atoms were studied using spin-unrestricted density functional theory (DFT) with a double numerical plus polarization basis set. This range of sizes gave enough information for establishing the general trends that were the primary goal of the study. Three different shapes of platinum clusters were presented, and the effect of cluster size on binding energy, total energy, and HOMO–LUMO energy gap was investigated. Subsequently, same calculations were performed for those selected Pt clusters with OH adsorbate on the surface. The results show that the stability of both the pure clusters and the clusters with adsorbed OH molecule increases with an increase of cluster size. This fact indicates that direct influence of the size of Pt cluster on the reaction rate is possible, and the understanding of how cluster size would affect binding energy is important. As expected, the effect of cluster size on total energy of molecule was shown to be a linear function independent of cluster type. We also found that optimized (stable) Pt clusters were bigger in size than that of the initial clusters, or clusters with bulk geometry. [ABSTRACT FROM AUTHOR]

Background/Aims: Long noncoding RNAs (lncRNAs) play important roles in stem cell differentiation. However, their role in osteogenesis of human adipose-derived stem cells (ASCs), a promising cell source for bone regeneration, remains unknown. Here, we investigated the expression profile and potential roles of lncRNAs in osteogenic differentiation of human ASCs. Methods: Human ASCs were induced to differentiate into osteoblasts in vitro, and the expression profiles of lncRNAs and mRNAs in undifferentiated and osteogenic differentiated ASCs were obtained by microarray. Bioinformatics analyses including subgroup analysis, gene ontology analysis, pathway analysis and co-expression network analysis were performed. The function of lncRNA H19 was determined by in vitro knockdown and overexpression. Quantitative reverse transcription polymerase chain reaction was utilized to examine the expression of selected genes. Results: We identified 1,460 upregulated and 1,112 downregulated lncRNAs in osteogenic differentiated human ASCs as compared with those of undifferentiated cells (Fold change ≥ 2.0, P < 0.05). Among these, 94 antisense lncRNAs, 85 enhancer-like lncRNAs and 160 lincRNAs were further recognized. We used 12 lncRNAs and 157 mRNAs to comprise a coding-non-coding gene expression network. Additionally, silencing of H19 caused a significantly increase in expression of osteogenesis-related genes, including ALPL and RUNX2, while a decrease was observed after H19 overexpression. Conclusion: This study revealed for the first time the global expression profile of lncRNAs involved in osteogenic differentiation of human ASCs and provided a foundation for future investigations of lncRNA regulation of human ASC osteogenesis.

Colony-stimulating factor 1 (CSF1) and interleukin 34 (IL34) signal via the CSF1 receptor to regulate macrophage differentiation. Studies in IL34- or CSF1-deficient mice have revealed that IL34 function is limited to the central nervous system and skin during development. However, the roles of IL34 and CSF1 at homeostasis or in the context of inflammatory diseases or cancer in wild-type mice have not been clarified in vivo. By neutralizing CSF1 and/or IL34 in adult mice, we identified that they play important roles in macrophage differentiation, specifically in steady-state microglia, Langerhans cells, and kidney macrophages. In several inflammatory models, neutralization of both CSF1 and IL34 contributed to maximal disease protection. However, in a myeloid cell-rich tumor model, CSF1 but not IL34 was required for tumor-associated macrophage accumulation and immune homeostasis. Analysis of human inflammatory conditions reveals IL34 upregulation that may account for the protection requirement of IL34 blockade. Furthermore, evaluation of IL34 and CSF1 blockade treatment during Listeria infection reveals no substantial safety concerns. Thus, IL34 and CSF1 play non-redundant roles in macrophage differentiation, and therapeutic intervention targeting IL34 and/or CSF1 may provide an effective treatment in macrophage-driven immune-pathologies.

A superwicking Ti-6Al-4V alloy material with a hierarchical capillary surface structure was fabricated using femtosecond laser. The basic capillary surface structure is an array of micropillars/microholes. For enhancing its capillary action, the surface of the micropillars/microholes is additionally structured by regular fine microgrooves using a technique of laser-induced periodic surface structures (LIPSS), providing an extremely strong capillary action in a temperature range between 23 °C and 80 °C. Due to strong capillary action, a water drop quickly spreads in the wicking surface structure and forms a thin film over a large surface area, resulting in fast evaporation. The maximum water flow velocity after the acceleration stage is found to be 225–250 mm/s. In contrast to other metallic materials with surface capillarity produced by laser processing, the wicking performance of which quickly degrades with time, the wicking functionality of the material created here is long-lasting. Strong and long-lasting wicking properties make the created material suitable for a large variety of practical applications based on liquid-vapor phase change. Potential significant energy savings in air-conditioning and cooling data centers due to application of the material created here can contribute to mitigation of global warming.

Autotetraploid rice is a useful rice germplasm for polyploid rice breeding. However, low fertility limits its commercial production. A neo-tetraploid rice with high fertility was developed from the progenies of crossing between autotetraploid lines by our research group. Our previous study showed that a myeloblastosis (MYB) transcription factor, MOF1, might be associated with the pollen development in tetraploid rice. However, little information is available about its role in pollen development in tetraploid rice. Here, we identified a new haplotype of MOF1 from neo-tetraploid rice and marked it as MOF1a. Transcriptome and qRT-PCR analysis demonstrated that MOF1a highly expressed in anthers, and displayed differential expression in neo-tetraploid rice compared to tetraploid rice line with low pollen fertility. The mutant (mof1a) of MOF1a, which was generated by CRISPR/Cas9 knockout in neo-tetraploid rice, showed low pollen fertility, and also exhibited abnormal tapetum and middle layer development, and defective chromosome behaviors during meiosis. A total of 13 tapetal related genes were found to be up-regulated in meiotic anthers of MOF1a compared with wild type plants by RNA-seq analysis, including CYP703A3, PTC1, and OsABCG26, which had been demonstrated to affect tapetal development. Moreover, 335 meiosis-related genes displayed differential expression patterns at same stage, including nine important meiosis-related genes, such as metallothionein OsMT1a. These results demonstrated that MOF1a plays an important role in pollen development and provides a foundation for understanding the molecular mechanism underlying MOF1a in reproduction of tetraploid rice.