Application of Patient-Reported Outcome Measurements in Adult Tumor Clinical Trials in China: Cross-Sectional Study.

BACKGROUND: International health policies and researchers have emphasized the value of evaluating patient-reported outcomes (PROs) in clinical studies. However, the characteristics of PROs in adult tumor clinical trials in China remain insufficiently elucidated. OBJECTIVE: This study aims to assess the application and characteristics of PRO instruments as primary or secondary outcomes in adult randomized clinical trials related to tumors in China. METHODS: This cross-sectional study identified tumor-focused randomized clinical trials conducted in China between January 1, 2010, and June 30, 2022. The ClinicalTrials.gov database and the Chinese Clinical Trial Registry were selected as the databases. Trials were classified into four groups based on the use of PRO instruments: (1) trials listing PRO instruments as primary outcomes, (2) trials listing PRO instruments as secondary outcomes, (3) trials listing PRO instruments as coprimary outcomes, and (4) trials without any mention of PRO instruments. Pertinent data, including study phase, settings, geographic regions, centers, participant demographics (age and sex), funding sources, intervention types, target diseases, and the names of PRO instruments, were extracted from these trials. The target diseases involved in the trials were grouped according to the American Joint Committee on Cancer Staging Manual, 8th Edition. RESULTS: Among the 6445 trials examined, 2390 (37.08%) incorporated PRO instruments as part of their outcomes. Within this subset, 26.82% (641/2390) listed PRO instruments as primary outcomes, 52.72% (1260/2390) as secondary outcomes, and 20.46% (489/2390) as coprimary outcomes. Among the 2,155,306 participants included in these trials, PRO instruments were used to collect data from 613,648 (28.47%) patients as primary or secondary outcomes and from 74,287 (3.45%) patients as coprimary outcomes. The most common conditions explicitly using specified PRO instruments included thorax tumors (217/1280, 16.95%), breast tumors (176/1280, 13.75%), and lower gastrointestinal tract tumors (173/1280, 13.52%). Frequently used PRO instruments included the European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire-30, the visual analog scale, the numeric rating scale, the Traditional Chinese Medicine Symptom Scale, and the Pittsburgh Sleep Quality Index. CONCLUSIONS: Over recent years, the incorporation of PROs has demonstrated an upward trajectory in adult randomized clinical trials on tumors in China. Nonetheless, the infrequent measurement of the patient's voice remains noteworthy. Disease-specific PRO instruments should be more effectively incorporated into various tumor disease categories in clinical trials, and there is room for improvement in the inclusion of PRO instruments as clinical trial end points.

HER2 Expression Associated with Clinical Characteristics and Prognosis of Urothelial Carcinoma in a Chinese Population.

BACKGROUND: The frequency of HER2 overexpression in bladder cancer is reported as 9%-61%. HER2 alteration correlates with aggressive disease in bladder cancer. Traditional anti-HER2 targeted therapy has failed to show clinical benefits in patients with advanced urothelial carcinoma . METHODS: The information on pathologically proven patients with urothelial carcinoma with detected HER2 status was collected from the database of Peking University Cancer Hospital. The HER2 expression, as well as its association with clinical characteristics and prognosis, was analyzed. RESULTS: A total of 284 consecutive patients with urothelial carcinoma were enrolled. HER2 was positive (IHC 2+/3+) in 44% of urothelial carcinoma. HER2 positivity was found more frequent in UCB than in UTUC (51% vs. 38%). Stage, radical surgery, and histological variant were associated with survival (P < .05). For metastatic patients, multivariate analysis shows that 3 indicators, including liver metastasis, the number of involved organs, and anemia, are independent risk factors of prognosis. Receiving immunotherapy or disitamab vedotin (DV) treatment is an independent protecting factor. The survival of patients with low HER2 expression was also significantly improved by the treatment of DV (P < .001). HER2 expression (IHC 1+, 2+, 3+) was associated with a better prognosis in this population. CONCLUSION: DV has improved the survival of patients with urothelial carcinoma in the real world. With the new-generation anti-HER2 ADC treatment, HER2 expression is no longer a poor prognostic factor.

The Photocatalytic Performance of P, Cl Doped Carboxylated Multiwalled Carbon Nanotube Modified Graphitic Carbon Nitride.

Graphitized carbonitride (g-C3N4) is widely used in CO2 reduction, hydrogen production, and degradation of toxic chemical dyes and antibiotics. It is a kind of photocatalytic material with excellent performance, and it has the advantages of being safe and nontoxic, having a suitable band gap (2.7 eV), and having a simple preparation and high stability, but because of its fast optical recombination speed and low visible light overutilization, the multifunctional application of g-C3N4 is seriously hindered. Compared with pure g-C3N4, MWCNTs/g-C3N4 have a red-shift in the visible range and a strong absorption in the visible region. Melamine and carboxylated multiwalled carbon nanotubes were used as raw materials to successfully prepare CMWCNT modified g-C3N4 doped with P, Cl by a high temperature calcination method. The effect of the addition amount of P, Cl on the photocatalytic performance of modified g-C3N4 was studied. The experimental results show that the multiwalled carbon nanotubes can accelerate the electron migration, and the doping of P, Cl elements can change the energy band structure of g-C3N4 and reduce the band gap. Through fluorescence analysis and photocurrent analysis, it is known that the incorporation of P, Cl reduces the recombination efficiency of photogenerated electron-hole pairs. In order to explore the application in the degradation of chemical dyes, the photocatalytic degradation efficiency of RhB under visible light was studied. The photocatalytic performance of the samples was evaluated by photodecomposition of aquatic hydrogen. The results showed that when the amount of ammonium dihydrogen phosphate was 10 wt %, the photocatalytic degradation efficiency was the highest, which was 21.13 times higher than that of g-C3N4.

Alcoholamine enhanced fractionation of cellulose from lignocellulosic biomass in ionic liquids.

Ionic liquid based technology is promising in the pretreatment of lignocelluloses. More efforts are still being made to intensify the separation of the main components in this biomass and to inhibit biopolymer degradation, especially in the fabrication of functional materials where excellent mechanical properties are often requisite. In this study, additives with amino and/or hydroxyl groups were proposed to improve the dissolution of lignocellulosic biomass in ionic liquids and to inhibit the degradation of cellulose. Among the tested additives (i.e., urea, L-2-aminobutyric acid, DL-aminopropanol, 3-aminopropanol and ethanolamine), 3-aminopropanol showed the best performance in enhancing wheat straw dissolution and cellulose recovery in 1-ethyl-3-methylimidazolium acetate ([EMIM]Ac). Further study revealed that this additive could also inhibit cellulose degradation in [EMIM]Ac. The interactions between the ionic liquid and additive were revealed by NMR and IR analysis. It was found that the formation of hydrogen bonds between 3-aminopropanol and [EMIM]Ac changed the interactions between ionic liquids and biomass, resulting in improved dissolution efficiency and inhibition of cellulose degradation. Optimization investigation showed that when using the 3-aminopropanol/[EMIM]Ac composite system as the solvent and pine as the raw biomass, the cellulose content in the recovered cellulose-rich material was increased from 33.3% (for the raw pine) to 66.9%. Correspondingly, the regenerated cellulose spinning in the composite system exhibited improved mechanical properties, with the elongation at break reaching 15.6% and the tensile fracture strength of 184.1 N per tex (in comparison with 9.6% for elongation at break and 99.7 N per tex for tensile fracture strength for the sample obtained in neat [EMIM]Ac).

Arctigenin derivatives improve exercise performance in mice: synthesis and biological evaluation.

Arctigenin (ARG) has potent antifatigue activity, but its clinical application has been restricted for its poor water solubility. In this study, seven ARG derivatives containing different amino acids coupled via an ethoxy linker were synthesized, and tested for their solubility, as well as activities to improve exercise performance in mice. All of the derivatives showed improved solubility compared to that of ARG. Derivative Z-A-6 exhibited the highest activity, showing that the mice ran a 4.88-fold greater distance in the running wheel test and swam a 2.86-fold greater time in the swimming test than those in the blank control group. Z-A-6 treatment increased the plasma superoxide dismutase and catalase concentrations as well as reduced lactic acid and blood urea nitrogen accumulation during exercise. Z-A-6 treatment enhanced the phosphorylation of adenosine monophosphate-activated protein kinase, and no acute toxicity was observed. The results will contribute to the development of potential antifatigue agents.

Self-Amplifying Iridium(III) Photosensitizer for Ferroptosis-Mediated Immunotherapy Against Transferrin Receptor-Overexpressing Cancer.

Photoimmunotherapy is attractive for cancer treatment due to its spatial controllability and sustained responses. This work presents a ferrocene-containing Ir(III) photosensitizer (IrFc1) that can bind with transferrin and be transported into triple-negative breast cancer (TNBC) cells via a transferrin receptor-mediated pathway. When the ferrocene in IrFc1 is oxidized by reactive oxygen species, its capability to photosensitize both type I (electron transfer) and type II (energy transfer) pathways is activated through a self-amplifying process. Upon irradiation, IrFc1 induces the generation of lipid oxidation to cause ferroptosis in TNBC cells, which promotes immunogenic cell death (ICD) under both normoxia and hypoxia. In vivo, IrFc1 treatment elicits a CD8+ T-cell response, which activates ICD in TNBC resulting in enhanced anticancer immunity. In summary, this work reports a small molecule-based photosensitizer with enhanced cancer immunotherapeutic properties by eliciting ferroptosis through a self-amplifying process.

Multi-channel higher-order OAM generation and switching based on a mode selective interferometer.

A multi-channel orbital angular momentum (OAM) mode generation and switching scheme is proposed and demonstrated based on an in-fiber mode selective interferometer (MSI), which is formed in a four-mode fiber. The MSI consists of two strong modulated long-period fiber gratings (LPFGs), which realizes the mode selected coupling between a target mode pair. With the optimized structural parameters, the MSI can couple a launched LP01 (or OAM0) into a desired higher-order azimuthal mode (HAM, LPl1 or OAM±l, l≥1) at multiple wavelength channels and generate the HAM with high-purity. To verify this concept, we fabricate two LPFGs in a four-mode fiber with designed distance and hence realize a MSI which can generate the second-order HAM (OAM2 or LP21) at 17 wavelength channels. The mode conversion efficiency is more than 90% at 17 wavelengths and the corresponding mode purity is no less than 97%, respectively. In addition, we also demonstrate that the selected mode pair (OAM0 and OAM2) can be switched at multiple channels by changing the state of the MSI. This MSI can also be used as a wavelength band-rejection filter on different spatial modes and find potential applications in optical communications and sensing.

High-mobility group AT-Hook 1 mediates the role of nuclear factor I/X in osteogenic differentiation through activating canonical Wnt signaling.

It was previously reported that the loss of the transcription factor nuclear factor I/X (NFIX) gene in mice impaired endochondral ossification and mineralization in bone. However, the cellular and molecular basis for the defect remains unexplored. In this study, we investigated if and how NFIX regulates osteoblast differentiation. Nfix mRNA was induced during osteogenic and adipogenic differentiation of progenitor cells. Loss-of-function and gain-of-function studies revealed that NFIX induced osteoblast differentiation and impaired adipocyte formation from progenitor cells. RNA-seq and promoter analysis revealed that NFIX transcriptionally stimulated the expression of high-mobility group AT-Hook 1 (HMGA1). We then demonstrated that HMGA1 stimulated osteogenic differentiation of progenitor cells at the expense of adipogenic differentiation. The effect of Nfix siRNA on the differentiation of progenitor cells could be attenuated when HMGA1 was simultaneously overexpressed. Further investigations revealed the stimulatory effect of NFIX and HMGA1 on canonical wingless-type MMTV integration site family (Wnt) signaling. HMGA1 transcriptionally activates the expression of low-density lipoprotein receptor-related protein 5. Finally, in vivo transfection of Nfix siRNA to the marrow of mice reduced osteoblasts and increased fat accumulation in the marrow, and inactivated HMGA1/ß-catenin signaling in bone marrow mesenchymal stem cells. This study suggests that HMGA1 plays a role in osteoblast commitment and mediates the function of NFIX through transcriptionally activating canonical Wnt signaling.

Hierarchical Fibrous Honeycomb Ceramics with High Load Capability and Low Light-Off Temperature for the Next-Generation Auto Emissions Standards.

Novel and stringent automotive exhaust gas emissions standards are urgently needed to counter the problems posed by the worsening global climate and environment. However, the traditional cordierite-based honeycomb ceramics substrates with ultimate pore density have seriously restricted the establishment of new emission standards. Herein, we introduce a novel robust substrate with tailored volume-specific surface area and low heat capacity. This substrate employs the synergy of high-strength ceramic fibers and ultrathin TiO2 nanosheets. The micro-sized fibers provide support to ensure structural strength during the catalytic reaction, while the nanosheets play the dual role of connecting the fibers and providing a high surface area for catalyst immobilization. The new three-dimensional (3D) microarchitecture exhibits a high volume-specific surface area of 3.59×104  cm2 /cm3 , a compressive strength of 2.01 MPa, and remarkable stability after high-speed air erosion at 800 °C. The honeycomb-like structure exhibit low resistance to gas flow. Furthermore, after loading with Pt and Pd nanoparticles, the composite 3D microarchitecture delivered an excellent catalytic performance and prominent structural stability, with a super low light-off temperature of 150 °C. The outstanding mechanical and thermal stability and the high surface area and light-off temperature of the new substrate indicate its potential for use as a highly efficient catalytic carrier to meet the next-generation auto emissions standards.

Synthesis and Applications of SAPO-34 Molecular Sieves.

Silicoaluminophosphate zeolite (SAPO-34) has been attracting increasing attention due to its excellent form selection and controllability in the chemical industry, as well as being one of the best industrial catalysts for methanol-to-olefin (MTO) reaction conversion. However, as a microporous molecular sieve, SAPO-34 easily generates carbon deposition and rapidly becomes inactivated. Therefore, it is necessary to reduce the crystal size of the zeolite or to introduce secondary macropores into the zeolite crystal to form a hierarchical structure in order to improve the catalytic effect. In this review, the synthesis methods of conventional SAPO-34 molecular sieves, hierarchical SAPO-34 molecular sieves and nanosized SAPO-34 molecular sieves are introduced, and the properties of the synthesized SAPO-34 molecular sieves are described, including the phase, morphology, pore structure, acid source, and catalytic performance, in particular with respect to the synthesis of hierarchical SAPO-34 molecular sieves. We hope that the review can provide guidance to the preparation of the SAPO-34 catalysts, and stimulate the future development of high-performance hierarchical SAPO-34 catalysts to meet the growing demands of the material and chemical industries.

Safety, activity, and pharmacokinetics of camrelizumab in advanced Asian melanoma patients: a phase I study.

BACKGROUND: Anti-programmed cell death receptor-1 (PD-1) monotherapy is the standard treatment for metastatic melanoma in current. Camrelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody whose safety and efficacy have not been reported in advanced Asian melanoma patients. METHODS: This phase I study investigated the safety, activity, and pharmacokinetics of camrelizumab in Chinese patients with advanced melanoma. The study included two phases, the dose-escalation phase ("3 + 3" design at 60 mg, 200 mg, and 400 mg) and the dose-expansion phase. RESULTS: No dose-limiting toxicities were recorded over the dose-escalation phase, and the maximum tolerated dose was not reached. The most common treatment-related adverse events (TRAEs) in 36 patients were reactive cutaneous capillary endothelial proliferation, followed by rash, fever, hypothyroidism, hyperthyroidism, vitiligo, and fatigue. Five grade 3 or above TRAEs were reported (13.9%), including two cases of elevated γ-glutamyltransferase and blood triglycerides without clinical symptoms, and one liver injury recovered after symptomatic treatment. The confirmed overall response rate was 13.9% (95%CI: 4.7, 29.5%) and disease control rate was 38.9% (95%CI: 23.1, 56.5%). The median progression-free survival was 1.8 months (95%CI: 1.1, 2.4) and the median overall survival was 11.1 months (95%CI: 6.8, 15.4). CONCLUSIONS: Camrelizumab had acceptable tolerability and similar anti-tumor activity compared with other anti-PD-1 antibodies in advanced Asian melanoma patients. TRIAL REGISTRATION: ClinicalTrials.gov identification: NCT02738489. Registered on 14/04/2016, prospectively registered.

Identification of the metabolites of methylophiopogonanone A by ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry.

RATIONALE: Methylophiopogonanone A (MOA) is a naturally occurring homoisoflavonoid from the Chinese herb Ophiopogon japonicus, which has been demonstrated to attenuate myocardial apoptosis. However, the metabolism of MOA remains unknown. The goal of the present work was to investigate the in vitro metabolism of MOA using liver microsomes and hepatocytes. METHODS: The metabolites were generated by incubating MOA with rat, monkey and human liver microsomes or hepatocytes. The resulting samples were analyzed by using a quadrupole-orbitrap high-resolution mass spectrometer. The metabolites were identified through the measurements of the exact mass, elemental composition and product ions. RESULTS: A total of 15 metabolites were detected and identified. Among these metabolites, M7 (demethylenation) was the most abundant metabolite in liver microsomes, while M6 (hydroxylation) was the predominant metabolite in hepatocytes, and glucuronidation metabolites (M9 and M10) were also the main metabolites in hepatocytes. The metabolic pathways of MOA included hydroxylation, demethylenation, glucuronidation, methylation, sulfation and glutathione conjugation. CONCLUSIONS: This study for the first time provides valuable data on the metabolites of MOA, which will be of great importance for a better understanding of its disposition and to predict human pharmacokinetics.

Circ_0049472 regulates the damage of Aß-induced SK-N-SH and CHP-212 cells by mediating the miR-107/KIF1B axis.

Alzheimer's disease (AD) is a neurodegenerative disease that seriously affects the life and health of the elderly. Studies have found that circular RNAs (circRNAs) are associated with human diseases, including AD. Hsa_circ_0049472 has been uncovered to be overexpressed in AD, but the role of circ_0049472 remains unclear. AD patients were recruited to collect cerebrospinal fluid (CSF) and serum samples. Amyloid beta (Aß)-induced SK-N-SH and CHP-212 cells were used as the AD cell models in vitro. Quantitative real-time PCR (qRT-PCR) was used to assess the expression of circ_0049472, microRNA-107 (miR-107) and kinesin family member 1B (KIF1B). Cell counting kit-8 assay tested the cell viability, and flow cytometry measured cell apoptosis. The levels of proliferating cell nuclear antigen (PCNA), BCL2 Associated X (Bax) and kinesin family member 1B (KIF1B) protein were examined by western blot. In addition, the relative inflammatory cytokines (TNF-α, IL-6 and IL-1ß) were detected by enzyme-linked immunosorbent assay (ELISA). The malondialdehyde (MDA) level and superoxide dismutase (SOD) activity were measured by relative kits. Dual-luciferase reporter assays and RNA pull-down assay verified the relationship between miR-107 and circ_0049472 or KIF1B. Circ_0049472 and KIF1B were overexpressed in AD patient-derived cerebrospinal fluid (CSF) and serum samples, as well as Aß-induced SK-N-SH and CHP-212 cells. Silencing circ_0049472 promoted cell proliferation, and inhibited cell apoptosis in Aß-induced SK-N-SH and CHP-212 cells. MiR-107 was a target of circ_0049472. MiR-107 silencing abolished the cell viability and apoptosis affected by down-regulation of circ_0049472 in Aß-induced SK-N-SH and CHP-212 cells. Besides, miR-107 targeted KIF1B, and overexpressed KIF1B reverted miR-107 elevation-mediated effects on cell apoptosis, inflammation, and oxidative stress of Aß-induced SK-N-SH and CHP-212 cells. Circ_0049472 modulated KIF1B by serving as a miR-107 decoy, thereby mediating Aß-induced neurotoxicity, suggesting that circ_0049472 may be involved in AD pathogenesis.

Tungsten-Based Nanocatalysts: Research Progress and Future Prospects.

The high price of noble metal resources limits its commercial application and stimulates the potential for developing new catalysts that can replace noble metal catalysts. Tungsten-based catalysts have become the most important substitutes for noble metal catalysts because of their rich resources, friendly environment, rich valence and better adsorption enthalpy. However, some challenges still hinder the development of tungsten-based catalysts, such as limited catalytic activity, instability, difficult recovery, and so on. At present, the focus of tungsten-based catalyst research is to develop a satisfactory material with high catalytic performance, excellent stability and green environmental protection, mainly including tungsten atomic catalysts, tungsten metal nanocatalysts, tungsten-based compound nanocatalysts, and so on. In this work, we first present the research status of these tungsten-based catalysts with different sizes, existing forms, and chemical compositions, and further provide a basis for future perspectives on tungsten-based catalysts.

Periodontal ligament cells derived small extracellular vesicles are involved in orthodontic tooth movement.

OBJECTIVES: Small extracellular vesicles (EVs) from human periodontal ligament cells (hPDLCs) are closely associated with periodontal homeostasis. Far less is known about EVs association with orthodontic tooth movement (OTM). This study aimed to explore the role of small EVs originated from hPDLCs during OTM. MATERIALS AND METHODS: Adult C57BL/6 mice were used. Springs were bonded to the upper first molars of mice for 7 days to induce OTM in vivo. To block small EVs release, GW4869 was intraperitoneally injected and the efficacy of small EVs inhibition in periodontal ligament was verified by transmission electron microscope (TEM). Tooth movement distance and osteoclastic activity were studied. In vitro, hPDLCs were isolated and administered compressive force in the EV-free culture media. The cell morphologies and CD63 expression of hPDLCs were studied. Small EVs were purified and characterized using a scanning electron microscope, TEM, western blot, and nanoparticle tracking analysis. The expression of proteins in the small EVs was further processed and validated using a human immuno-regulated cytokines array and an enzyme-linked immunosorbent assay (ELISA). RESULTS: The small EV depletion significantly decreased the distance and osteoclastic activity of OTM in the mice. The hPDLCs displayed different morphologies under force compression and CD63 expression level decreased verified by western blot and immunofluorescence staining. Small EVs purified from supernatants of the hPDLCs showed features with <200 nm diameter, the positive EVs marker CD63, and the negative Golgi body marker GM130. The number of small EVs particles increased in hPDLCs suffering force stimuli. According to the proteome array, the level of soluble intercellular adhesion molecule-1 (sICAM-1) displayed the most significant fold change in small EVs under compressive force and this was further confirmed using an ELISA. LIMITATIONS: Further mechanism studies are warranted to validate the hPDLC-originated small EVs function in OTM through proteins delivery. CONCLUSIONS: The notable decrease in the OTM distance after small EV blocking and the significant alteration of the sICAM-1 level in the hPDLC-originated small EVs under compression provide a new vista into small EV-related OTM biology.

Construction and Evaluation of Traceable rhES-QDs-M-MS Protein Delivery System: Sustained-Release Properties, Targeted Effect, and Antitumor Activity.

Recombinant human endostatin (rhES) is a protein drug with poor stability and short in vivo circulation time. The present study was therefore aimed at developing sustained-release lung targeted microspheres drug delivery system and evaluating its targeting efficiency using in vivo imaging techniques with quantum dots (QDs) as the imaging material. The oil-soluble QDs were coated with amphiphilic polymers to obtain a polymer-quantum dots micelle (QDs-M) with the potential to stably disperse in water. The rhES and QDs-M were combined using covalent bonds. The rhES-QDs-M microspheres (rhES-QDs-M-MS) were prepared using electrostatic spray technology and also evaluated via in vivo imaging techniques. The pharmacodynamics was further studied in mice. The rhES-QDs-M-MS (4-8 µm) were stable in an aqueous medium with good optical properties. The in vitro studies showed that the rhES-QDs-M-MS had sustained release which was maintained for at least 15 days (cumulative release >80%) without any burst release. The rhES-QDs-M-MS had a very high safety profile and also effectively inhibited the in vitro proliferation of human umbilical vein endothelial cells by about 70%. The pharmacokinetic results showed that the rhES could still be detected at 72 h in the experimental group which meant that the rhES-QDs-M-MS had a significant sustained-release effect. The rhES-QDs-M-MS had a better lung targeting effect and higher antitumor activity compared with the rhES. The traceable rhES-QDs-M-MS served as a promising drug delivery system for the poorly stable rhES proteins and significantly increased its lung-targeted effect, sustained-release properties, and antitumor activities.

Lysophosphatidic acid receptor 4 regulates osteogenic and adipogenic differentiation of progenitor cells via inactivation of RhoA/ROCK1/ß-catenin signaling.

Recent evidence revealed that lysophosphatidic acid receptor 4 (LPAR4) plays a role in osteogenesis and bone remodeling in mice. However, the molecular mechanism by which LPAR4 controls osteogenic and adipogenic differentiation of mesenchymal progenitor cells remains pending. In the current study, our data showed that Lpar4 was expressed in bone and adipose tissue and the expression increased during osteoblast and adipocyte differentiation. Lpar4 overexpression in stromal ST2 and preosteoblastic MC3T3-E1 cells inhibited osteogenic differentiation. By contrast, Lpar4 overexpression in ST2 and mesenchymal C3H10T1/2 cells enhanced adipogenic differentiation. Conversely, depletion of endogenous Lpar4 in the progenitor cells induced osteogenic differentiation and inhibited adipogenic differentiation. Furthermore, enhanced osteoblast differentiation and alleviated fat accumulation were observed in marrow of mice after in vivo transfection of Lpar4 siRNA. Mechanism investigations revealed that LPAR4 inhibited the activation of ras homolog family member A (RhoA)/Rho-associated kinases 1 (ROCK1) and canonical Wnt signal pathways. ROCK1 was shown to be able to activate Wnt/ß-catenin pathway. We further demonstrated that the overexpression of ROCK1 stimulated osteogenic differentiation and restrained adipogenic differentiation from stromal progenitor cells. Moreover, overexpression of ROCK1 attenuated the inhibition of osteogenic differentiation by LPAR4. The current study has provided evidences demonstrating that RhoA/ROCK1 activates ß-catenin signaling to promote osteogenic differentiation and conversely restrain adipogenic differentiation. The inactivation of RhoA/ROCK1/ß-catenin signaling is involved in LPAR4 regulation of the directional differentiation of marrow stromal progenitor cells.

Triclinic Layered A2ZnSi3S8 (A = Rb and Cs) with Large Optical Anisotropy and Systematic Research on the Inherent Structure-Performance Relationship in the A2MIIBMIV3Q8 Family.

Two triclinic A2ZnSi3S8 (A = Rb and Cs) with layered structures were successfully synthesized, and their physicochemical performances including optical bandgap, thermal behavior, and optical anisotropy were investigated. A2ZnSi3S8 could be viewed as the first discovered Si-based examples in the known A2MIIMIV3Q8 family (2-1-3-8 system; A = monovalent alkali metal; MII = divalent transition metal; MIV = group 14 metal; Q = chalcogen). The A2MIIMIV3Q8 family members crystallize in five different space groups (P1̅, P21, P21/n, P212121, and Pa3̅), and their structural transformation and optical performances (bandgap, NLO coefficient, and birefringence) were systematically studied based on the first-principles calculation among 13 A2MIIBMIV3Q8 (MIIB = Zn, Cd, and Hg) compounds without cubic ß-K2ZnSn3S8. Research result shows that the above 13 compounds exhibit the layered structures, but diverse wavelike layers and their optical anisotropy (Δn) undergo an increasing trend range from the triclinic to orthorhombic systems. Moreover, P212121 compounds have very weak NLO effects compared with those of the P21 compounds since the polarization directions of anionic groups (MIIBQ4 and MIVQ4) in P212121 compounds are directing oppositely and almost completely canceled out by the dipole moment calculation, which further indicates that P21 compounds exhibiting the relatively strong NLO effect and large optical anisotropy could be expected as potential IR NLO candidates.

Polydopamine Nanocluster Embedded Nanofibrous Membrane via Blow Spinning for Separation of Oil/Water Emulsions.

Developing a porous separation membrane that can efficiently separate oil-water emulsions still represents a challenge. In this study, nanofiber membranes with polydopamine clusters polymerized and embedded on the surface were successfully constructed using a solution blow-spinning process. The hierarchical surface structure enhanced the selective wettability, superhydrophilicity in air (≈0°), and underwater oleophobicity (≈160.2°) of the membrane. This membrane can effectively separate oil-water emulsions, achieving an excellent permeation flux (1552 Lm-2 h-1) and high separation efficiency (~99.86%) while operating only under the force of gravity. When the external driving pressure was increased to 20 kPa, the separation efficiency hardly changed (99.81%). However, the permeation flux significantly increased to 5894 Lm-2 h-1. These results show that the as-prepared polydopamine nanocluster-embedded nanofiber membrane has an excellent potential for oily wastewater treatment applications.

Multiple orbital angular momentum mode switching at multi-wavelength in few-mode fibers.

Mode division multiplexing has attracted great attention because it can potentially overcome the limitation of single-mode fiber traffic capacity. However, it has been challenging to realize multiple modes controlling and switching due to the intrinsic overlap of the modes in the transmission waveguide. As a solution, we propose a cascaded phase-shifted long-period fiber grating (PS-LPFG) based multiple mode switching scheme. Using the PS-LPFGs, the multiple guided orbital angular momentum (OAM) modes selective controlling and switching at multi-wavelength can be achieved in few-mode fibers by regulating the grating resonance condition. In principle, a N × N mode switch matrix can be realized by cascading CN2 gratings, where each grating acts as a mode switch element to achieve a couple selected OAM mode switching and meanwhile the other modes are under nonblocking status. As a proof of the concept, a 2 × 2 mode switching between two OAM modes at different wavelengths based on one PS-LPFG element is demonstrated in our experiments. The switching efficiency of the two modes at two wavelengths 1537nm and 1558nm are ∼98.4% and ∼98.7%, respectively. The proposed multiple OAM mode switch has potential applications in the future hybrid multi-dimensional multiplexing optical fiber communication systems.