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In this paper, we devote ourselves to studying robust error bounds for a convex inequality system in the face of data uncertainty. Under the assumption that uncertain sets are convex compact, we present a sufficient condition for the existence of robust error bounds of the uncertain convex inequality system by means of the associated recession cone and recession functions. When the uncertain sets are only compact, we establish a necessary and sufficient condition for the uncertain convex inequality system to possess a robust error bound by the Ekeland variational principle. As an immediate application, we obtain robust error bounds for the uncertain convex polynomial inequality system. [ABSTRACT FROM AUTHOR]

AimTo identify optimally therapeutic exercise interventions for improving motor ability among patients with Parkinson’s disease (PD), we conducted a network meta-analysis (NMA) of randomized controlled trials comparing different exercise regimens.MethodsRelevant RCTs were retrieved by searching PubMed, Embase, Cochrane, Web of Science, CINAHL, CBM, China National Knowledge Infrastructure (CNKI), Wan fang, VIP, and other databases from inception to July 9, 2023 is available in English as the primary language. Exercise outcomes as measured by Movement Disorder Society- Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS-III) score change were evaluated and ranked using STATA software version 18.0. All included studies were assessed for methodological quality using the Cochrane Risk of Bias tool.ResultsThe final NMA included 71 studies involving 3,732 participants, 87 intervention experiments, and 27distinct interventions. Although most exercise interventions showed some efficacy (reducing MDS-UPDRS-III score), cumulative ranking probability surface (SUCRA) values indicated that the best exercise interventions for motor function improvement were archery (95.6%), riding a bicycle (80.9%), and binary rhythm dance (80.8%).ConclusionAn exercise intervention comprising archery, cycling, and(or) binary rhythm dance may yield superior improvements in motor function among patients with Parkinson’s disease.

[Objective] The change characteristics and influencing factors of vegetation coverage and its spatial distribution in the Binchang mining area were analyzed, and the ecological status of the mining area was evaluated in order to provide a scientific reference and theoretical basis for reclamation and ecological restoration of the mining area. [Methods] Landsat Surface Reflectance Tier 1 data (30 m resolution) from 1986 to 2021 were obtained from the Google Earth Engine cloud platform. Based on a pixel binary model, the trend analysis method and F-test were used to quantitatively analyze the temporal and spatial variation of vegetation coverage in the Binchang mining area over many years. Geodetector was used to analyze the spatial heterogeneity of vegetation coverage. [Results] ① Vegetation coverage in the Binchang mining area increased from 1986 to 2021, and the overall growth trend was good (average growth rate of 0.64%/a). The average multi-year vegetation coverage in the study area was relatively high, with the area of medium coverage and greater accounting for 87.14% of the total area. The spatial distribution was characterized as “higher in the southeast and lower in the northwest”. ② In terms of the change trend of vegetation coverage, the study area was dominated by significantly improved areas, accounting for 56.65% of the total area. However, there were still some areas with significant vegetation degradation, mainly concentrated in the area near urban river roads. ③ The factors influencing vegetation coverage followed the order of slope > elevation > annual precipitation > GDP> population density > annual average temperature > vegetation type > soil type. The interaction between slope and annual precipitation had the strongest influence on the spatial heterogeneity of vegetation coverage. [Conclusion] From 1986 to 2021, the vegetation coverage in the Binchang mining area was good, showing a significant growth trend as a whole, and the vegetation improvement was obvious. The dominant factor affecting the spatial heterogeneity of vegetation coverage in the study area was slope.

Objective To investigate the effect of FOCUS-PDCA management mode in standardizing medication of ophthalmic drugs in patients undergoing ambulatory eye surgery, and provide reference for continuous improvement of the nursing quality of ambulatory eye surgery. Methods A non-concurrent control trial was conducted, and patients undergoing ambulatory eye surgery were assigned to the control group (n=146)and the observation group (n=154). The control group received routing nursing management during operation period. The FOCUS-PDCA management mode was adopted in standardizing medication of ophthalmic drugs for patients in the observation group. The rate of qualified self-medication of ophthalmic drugs, awareness and knowledge about ophthalmic drugs and patient satisfaction were measured and compared between groups. Results The rates of proper storage of ophthalmic drugs, proper administration time of ophthalmic drugs and qualified self-medication of ophthalmic drugs in the observation group were higher than those in the control group (P

An on-line pyrolysis-vacuum ultraviolet photoionization mass spectrometer was built for the analysis of pyrolysis products of tobacco. Vacuum ultraviolet photoionization is a “soft” ionization method producing few or no fragments of molecular ions, and identifing the complex pyrolysis products in real time. In this work, the pyrolysis of tobacco leaves from various stalk positions (B2F, C3F and X2F) at 300, 400, 500, 600 and 700 ℃, and the effects of reaction temperature on the pyrolysis products intensity were studied. A series of mass spectra of pyrolysis products were obtained, and the changes of products at different pyrolysis temperatures were compared. The analysis results of products at different pyrolysis temperatures were helpful to reveal the formation mechanism of compounds in different parts of cut tobacco during pyrolysis/combustion. The dynamic curves of pyrolysis products such as vinylamine (m/z 43), isoprene (m/z 68) and dimethylfuran (m/z 96) with time were further observed at 500 ℃, so as to master the dynamic change process of pyrolysis reaction. It was found that the increase of temperature can dramatically shorten the reaction time. Generally, the primary products will be formed at the medium cracking temperature, and gradually pyrolyzed into secondary products with the increase of temperature, the secondary products will be accompanied by higher temperature cracking and thermal synthesis to form tertiary products. In order to quickly screen and identify different parts of tobacco, principal component analysis (PCA) was used to analyze the mass spectra of pyrolysis products, and the differences of chemical components in different parts of tobacco were identified. Then, the components with m/z 58, 96, 110 were the typical products of X2F, the components with m/z 43, 126 were the representative products of C3F, and the main representative product of B2F was the component with m/z 84. Based on the above results, photoionization mass spectrometry was important to study the dynamic changes of tobacco pyrolysis products, the pyrolysis products of different parts of tobacco were quickly identified at 300-700 ℃, and the main pyrolysis products were summarized. By comprehensively evaluating the main components and relative content of pyrolysis products, tobacco samples from different parts can be quickly distinguished.

In this paper, we investigate robust optimality conditions of convex multiobjective optimization problems with data uncertainty by ε-constraint scalarization method and image space analysis. We firstly present the concepts of robust solutions to convex multiobjective optimization problems with data uncertainty. The relationships between robust solutions of uncertain convex multiobjective optimization problem and that of its corresponding ε-constraint optimization problem are also obtained. Besides, we employ the image space analysis to establish a theorem of alternative for the ε-constraint robust optimization, which allows to get the robust optimality conditions of optimal solutions of the ε-constraint robust optimization. Lastly, we establish the sufficient and necessary optimality conditions of the robust efficient solutions for convex multiobjective optimization problems with data uncertainty. [ABSTRACT FROM AUTHOR]

Objective To investigate whether hypocalcemia is associated with poor prognosis in COVID-19 patients. Methods A retrospective analysis was performed on 2 651 COVID-19 patients admitted to Wuhan Huoshenshan Hospital from February 4, 2020 to April 11, 2020. They were divided into low and normal calcium groups according to their serum calcium level lower than 2.11 mmol/L or not. Their basic demographic characteristics, results of laboratory tests, treatment, complications and outcomes were analyzed and compared between the 2 groups. COX regression model was used to analyze whether low calcium is an independent risk factors for poor outcomes in COVID-19 patients. Results The low calcium group had significantly higher ratios of mechanical ventilation, extracorporeal membrane oxygenation (ECMO) and ICU occupancy (P < 0.05); obviously higher incidences of sepsis, shock, hypoproteinemia, respiratory failure, coagulation disorders, acute kidney injury, acute myocardial injury, acute respiratory distress syndrome (ARDS), and even mortality (P < 0.05); and remarkably longer length of hospital stay (P < 0.001) when compared with the normal calcium group. The blood calcium level of mild and common, severe, and critical COVID-19 patients was 2.17 (2.11, 2.24), 2.13 (2.04, 2.21), and 2.03 (1.89, 2.18) mmol/L, respectively, and significant differences were seen among the patients (P < 0.05). The calcium level was in a decreasing trend with the severity of COVID-19 (P < 0.05). The calcium level was statistically lower in the dead patients than those survival [1.97 (1.87, 2.03) vs 2.17 (2.09, 2.23), P < 0.001]. Multivariate Cox regression analysis indicated that serum calcium concentration < 2.11 mmol/L was an independent risk factor for poor prognosis of COVID-19 (HR=5.695, 95%CI : 2.363~13.725, P < 0.001). Conclusion Low blood calcium level is an independent risk factor for poor prognosis in COVID-19 patients. Correction for hypocalcemia may be an important strategy to improve the prognosis of COVID-19 patients.

The influence of different multi-stage aging heat treatment on microstructure and corrosion resistance of 7056 alloy was investigated by the measurements of transmission electron microscope(TEM), scanning electron microscope(SEM),mechanical properties and electrical conductivity, exfoliation corrosion, slow strain rate testing(SSRT), Tafel cyclic polarization. The results show that after over-aging and re-aging heat treatment, the solute atoms precipitate again, and the volume fraction of the precipitate in the matrix increases, the grain boundary precipitates coarsen and become discontinuous, the precipitate-free zone becomes wider. Compared with 120℃/24h pre-aging,120℃/6h has advantage in terms of dissolution of finer precipitates and the growth of large coarse phase. Re-aging heat treatment can improve the strength and conductivity of over-aging alloys;compared with peak aging and retrogression and re-aging, the loss of tensile strength of the alloy is not significant, while the conductivity increases obviously. After over-aging and re-aging heat treatment, continuous anodic dissolution is avoided effectively, and the exfoliation corrosion resistance and stress corrosion cracking is enhanced.

Objective To investigate the effects of store-operated calcium entry (SOCE) on the bio-functions of vascular endothelial cells (ECs) based on human umbilical vein endothelial cells (HUVECs). Methods The cultured HUVECs were divided into control group and 2-APB (SOCE inhibitor, 10, 25, 50, 75 and 100 μmol/L) intervention groups. The SOCE was measured by the fluorescence intensity of calcium probe in 5 min after 2-APB treatment (n=10). The proliferation (n=9) and migration (n=10) capacities of HUVECs after different doses of 2-APB treatment (50, 75 and 100 μmol/L) for 24 h were measured by CCK-8 assay and Transwell assay. In addition, at 2 h after 2-APB treatment, Griess reagent kit was employed to detect the production of NO (n=6), and Western blotting was used to measure the expression of eNOS (n=3) in different groups. Results Low doses of 2-APB (10 and 20 μmol/L) showed an inhibitory effect on SOCE, but the inhibition had no statistical significance (P < 0.05), while high doses of 2-APB (50, 75 and 100 μmol/L) inhibited SOCE significantly (P>0.05). Treatment of 2-APB (50, 75 and 100 μmol/L) also suppressed the proliferation (decreased by 33.2%, 46.3% and 61.2%, respectively when compared with control cells, all P < 0.05), the migration (decreased by 33.5%, 54.3% and 64.9%, respectively when compared with control cells, all P < 0.05), NO production (decreased by 40.5%, 61.9% and 73.1%, respectively when compared with control cells, all P < 0.05) as well as the synthesis of eNOS (decreased by 45.1% and 62.4% in the 75 and 100 μmol/L treated cells, respectively when compared with control cells, both P < 0.05) in ECs. Conclusion SOCE is involved in the proliferation and migration of ECs, and inhibition of SOCE can induce ECs dysfunction, which may act through suppressing eNOS synthesis.

The local expansion method is a novel and promising community detection algorithm. Just based on part of network information, it can detect overlapping communities effectively, but some problems exist such as seed node aggregation, poor quality and inaccurate community coverage. Therefore, we propose a local expansion overlapping community detection algorithm based on dispersed seeds. There are four essential parts of this algorithm: 1) We firstly generate non-overlapping partitions of the network, and locate seed nodes with the largest influence in their own partition by using a new index of node influence, which combines the information centrality of nodes and the number of k-order neighbors. 2) Secondly, on the condition of the neighborhood overlap measure maximization, seed nodes merge unseeded nodes to generate a preliminary seed community; 3) Then based on the community conductance gain, the allocated nodes are screened and the free nodes are assigned to the seed community; 4) In the end, a node-community similarity based on common connection edge is proposed to re-allocate new free nodes and obtain the final community structure. This method can make the community distribution more proper and the coverage more reasonable. The experimental results on some artificial data and real network data show that the algorithm performs well on overlapping community indicators such as EQ and ONMI, while the community detection results are more stable.

The effect of high buoyancy forces due to density contrast between the fluids on either side of the vent on the discharge coefficient Cd is taken into account in the laboratory. Salt water experiments are conducted at small scale in a large fresh water tank with saline to generate buoyancy force. In non-Boussinesq cases, a larger discharge parameter Γd at the vent may make plume-like flow contract further with a smaller value of the discharge coefficient. A nearly twofold time in the non-dimensional form for draining light fluid fully out of the space is observed comparing with time predicted with a constant value of Cd = 0.6 for simple draining flows. A displacement flow theoretical model with virtual source correction at the initial position of an internal source is developed to reveal a time-dependent movement of the layer interface, and the oscillatory amplitude of the interface overshooting during the transient period is found to depend on the two dimensionless geometrical parameters Λ and Θ.

A drug delivery system based on carboxymethyl cellulose-grafted graphene oxide loaded by methotrexate (MTX/CMC-GO) with pH-sensitive and controlled drug-release properties was developed in this work. CMC was grafted on graphene oxide by ethylenediamine through hydrothermal treatment. CMC serves as a pH-sensitive trigger, while CMC-GO serves as a drug-carrying vehicle due to the curved layer and large plain surface. Different amounts of drugs could be loaded into CMC-GO nanocarriers by control of the original amount of drug/carrier ratios. Additionally, low cytotoxicity against NIH-3T3 cells and low in vivo toxicity was observed. In vivo tumor growth inhibition assays showed that MTX/CMC-GO demonstrated superior antitumor activity than free MTX against HT-29 cells. Moreover, prolonged survival time of mice was observed after MTX/CMC-GO administration. The MTX/CMC-GO drug delivery system has a great potential in colon cancer therapy.

Alien species may adversely affect not only human health, agriculture, and fisheries but also the native ecosystem. Pomacea canaliculata is one of alien harmful species (IUCN). Forest residues are a kind of renewable, cheap and secure source of primary energy. Nandina domestica Thunb. is a commonly and widely cultivated plant for city landscape construction in China. After being pruned, a large of N. domestica leaves are usually abandoned. In this work, extracts of ethanol Soxhlet (SE), ethanol immerse (EE), and water immerse (WE) were obtained from leaves of N. domestica Thunb. cv. Firepower. The molluscicidal effects of the three extracts from the leaves were evaluated against black P. canaliculata. In sand pot culture condition and pot culture with paddy soil condition, SE at concentration of 4000 mg L-1 did not affect seedlings normal growth. Plant height, seedling fresh weight (SFW), seedling dry weight (SDW) and Chlorophyll content of SE (4000 mg L-1) were not significantly different from that in DS (distilled water + seedlings). Besides, in pot culture with paddy soil condition, the SE treatment at concentration of 4000 mg L-1 inhibited P. canaliculata chewing rice seedlings effectively, which was not statistically different from the positive control {NSP, niclosamide (according to field dosage, 0.086 g m-2 ) + seedlings + P. canaliculata)}. Results from this study indicated that SE has molluscicidal effect against P. canaliculata and SE did not affect the normal growth of rice seedlings. Thus, we suggest further chemical and toxicological studies of SE.

Pancreatic cancer is a kind of malignant tumor with high mortality rate. Early operation and late chemoradiotherapy are the treatment criteria, but the prognosis is still poor. Berberine, an alkaloid compound present in many herbal plants, is capable of inducing oxidative DNA damage and downregulating homologous recombination repair (HRR) in cancer cells. Poly (ADP ribose) polymerase-1 (PARP-1) is a sensor of DNA damage with key roles in DNA repair. In this study, we demonstrated that berberine and PARP inhibitor olaparib have a synthetic lethal effect on pancreatic cancer cells. The expression level of RAD51 were reduced by berberine. Correspondingly, PARP became hyperactivated in response to berberine treatment. When berberine is combined with olaparib, the expression of Rad51 and Parp are inhibited. The combination of berberine and olaparib synergistically inhibit cell activity and induce cell apoptosis. In addition, the synergistic effect of berberine and olaparib can be reversed by apoptosis inhibitor and necrosis inhibitor. Together, the results indicate that berberine combined with olaparib have a synthetic lethal effect on pancreatic cancer cells.

To study the deformation and stress of ring-flexspline in harmonic gear under actual working conditions,an interference fit model is applied to solve the problem of assembling between the wave generator and flexspline with large deformation. Further more experiments are performed to test the validity of this method. Then the finite element numerical calculations of the whole harmonic gear are obtained under no-load and rated load on the base of the model. At last,the deformation and stress distributions law of flexspline in the no-load and load are analyzed by data processing. The results show that the stress distribution of the flexspline has its minor value along the neutral layer of flexspline ring,and the maximum stress is located on the tooth root which mainly is tangential. The deformation and stress increment of flexspline under rated load are0. 46% and 93. 6% respectively relative to the no-load. It also shows that the load has little effect on flexspline deformation,but a strong influence on its stress. The finite element analysis results which fit well with related literature calculations proved that the interference fit model is effective,so it can provide a more precise method to study harmonic gear drive in accordance with the actual working conditions.

According to the fact that the traditional manual management method can not solve the problem of frequent accidents in the engineering construction process, the integrated scheme of safety prevention based on BIM and RFID is put forward, and the principle and technical feasibility of the integrated scheme are analyzed. Based on the integration technology scheme, the multi-layer architecture design pattern is adopted, and the software hierarchy of the integration system is designed in detail. On this basis, the integrated application network for engineering construction safety control is analyzed and designed by using the technology based on BIM and RFID. The research results of this paper provide a feasible technical reference scheme for the automatic identification and dynamic monitoring and early warning of the hidden dangers in the construction site.

Abstract Cancer is the leading cause of death worldwide. Nanomaterials and nanotechnologies could provide potential solutions. In this research, a novel biodegradable poly(lactide-co-glycolide)-d-a-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) random copolymer was synthesized from lactide, glycolide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization using stannous octoate as catalyst. The obtained random copolymers were characterized by 1H NMR, FTIR, GPC and TGA. The docetaxel-loaded nanoparticles made of PLGA-TPGS copolymer were prepared by a modified solvent extraction/evaporation method. The nanoparticles were then characterized by various state-of-the-art techniques. The results revealed that the size of PLGA-TPGS nanoparticles was around 250 nm. The docetaxel-loaded PLGA-TPGS nanoparticles could achieve much faster drug release in comparison with PLGA nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated by CLSM, demonstrating the fluorescence PLGA-TPGS nanoparticles could be internalized by human cervix carcinoma cells (HeLa). The results also indicated that PLGA-TPGS-based nanoparticles were biocompatible, and the docetaxel-loaded PLGA-TPGS nanoparticles had significant cytotoxicity against Hela cells. The cytotoxicity against HeLa cells for PLGA-TPGS nanoparticles was in time- and concentration-dependent manner. In conclusion, PLGA-TPGS random copolymer could be acted as a novel and promising biocompatible polymeric matrix material applicable to nanoparticle-based drug delivery system for cancer chemotherapy.

Abstract Multidrug resistance (MDR) in tumor cells is a significant obstacle to the success of chemotherapy in many cancers. The purpose of this research is to test the possibility of docetaxel-loaded poly (ε-caprolactone)/Pluronic F68 (PCL/Pluronic F68) nanoparticles to overcome MDR in docetaxel-resistance human breast cancer cell line. Docetaxel-loaded nanoparticles were prepared by modified solvent displacement method using commercial PCL and self-synthesized PCL/Pluronic F68, respectively. PCL/Pluronic F68 nanoparticles were found to be of spherical shape with a rough and porous surface. The nanoparticles had an average size of around 200 nm with a narrow size distribution. The in vitro drug release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake of PCL/Pluronic F68 nanoparticles in docetaxel-resistance human breast cancer cell line, MCF-7 TAX30, when compared with PCL nanoparticles. The cytotoxicity of PCL nanoparticles was higher than commercial Taxotere®in the MCF-7 TAX30 cell culture, but the differences were not significant (p > 0.05). However, the PCL/Pluronic F68 nanoparticles achieved significantly higher level of cytotoxicity than both of PCL nanoparticles and Taxotere®(p < 0.05), indicating docetaxel-loaded PCL/Pluronic F68 nanoparticles could overcome multidrug resistance in human breast cancer cells and therefore have considerable potential for treatment of breast cancer.

Abstract Background Nucleic acid amplification tests (NAATs) have offered hope for rapid diagnosis of tuberculosis (TB). However, their efficiency with smear-negative samples has not been widely studied in low income settings. Here, we evaluated in-house PCR assay for diagnosis of smear-negative TB using Lowenstein-Jensen (LJ) culture as the baseline test. Two hundred and five pulmonary TB (PTB) suspects with smear-negative sputum samples, admitted on a short stay emergency ward at Mulago Hospital in Kampala, Uganda, were enrolled. Two smear-negative sputum samples were obtained from each PTB suspect and processed simultaneously for identification of MTBC using in-house PCR and LJ culture. Results Seventy two PTB suspects (35%, 72/205) were LJ culture positive while 128 (62.4%, 128/205) were PCR-positive. The sensitivity and specificity of in-house PCR for diagnosis of smear-negative PTB were 75% (95% CI 62.6-85.0) and 35.9% (95% CI 27.2-45.3), respectively. The positive and negative predictive values were 39% (95% CI 30.4-48.2) and 72.4% (95% CI 59.1-83.3), respectively, while the positive and negative likelihood ratios were 1.17 (95% CI 0.96-1.42) and 0.70 (95% CI 0.43-1.14), respectively. One hundred and seventeen LJ culture-negative suspects (75 PCR-positive and 42 PCR-negative) were enrolled for follow-up at 2 months. Of the PCR-positive suspects, 45 (60%, 45/75) were still alive, of whom 29 (64.4%, 29/45) returned for the follow-up visit; 15 (20%, 15/75) suspects died while another 15 (20%, 15/75) were lost to follow-up. Of the 42 PCR-negative suspects, 22 (52.4%, 22/42) were still alive, of whom 16 (72.7%, 16/22) returned for follow-up; 11 (26.2%, 11/42) died while nine (21.4%, 9/42) were lost to follow-up. Overall, more PCR-positive suspects were diagnosed with PTB during follow-up visits but the difference was not statistically significant (27.6%, 8/29 vs. 25%, 4/16, p = 0.9239). Furthermore, mortality was higher for the PCR-negative suspects but the difference was also not statistically significant (26.2% vs. 20% p = 0.7094). Conclusion In-house PCR correlates poorly with LJ culture for diagnosis of smear-negative PTB. Therefore, in-house PCR may not be adopted as an alternative to LJ culture.

Abstract Background TC-2559 is a selective α4β2 subtype of nicotinic acetylcholine receptor (nAChR) partial agonist and α4β2 nAChR activation has been related to antinociception. The aim of this study is to investigate the analgesic effect of TC-2559 and its underlying spinal mechanisms. Results 1) In vivo bioavailability study: TC-2559 (3 mg/kg) had high absorption rate in rats with maximal total brain concentration reached over 4.6 μM within first 15 min after administration and eliminated rapidly with brain half life of about 20 min after injection. 2) In vivo behavioral experiments: TC-2559 exerts dose dependent antinociceptive effects in both formalin test in mice and chronic constriction injury (CCI) model in rats by activation of α4β2 nAChRs; 3) Whole-cell patch-clamp studies in the superficial dorsal horn neurons of the spinal cord slices: perfusion of TC-2559 (2 μM) significantly increased the frequency, but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). The enhancement of sIPSCs was blocked by pre-application of DHβE (2 μM), a selective α4β2 nicotinic receptor antagonist. Neither the frequency nor the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) of spinal dorsal horn neurons were affected by TC-2559. Conclusions Enhancement of inhibitory synaptic transmission in the spinal dorsal horn via activation of α4β2 nAChRs may be one of the mechanisms of the antinociceptive effects of TC-2559 on pathological pain models. It provides further evidence to support the notion that selective α4β2 subtype nAChR agonist may be developed as new analgesic drug for the treatment of neuropathic pain.

Abstract Three types of nanoparticle formulation from biodegradable PLGA-TPGS random copolymer were developed in this research for oral administration of anticancer drugs, which include DMAB-modified PLGA nanoparticles, unmodified PLGA-TPGS nanoparticles and DMAB-modified PLGA-TPGS nanoparticles. Firstly, the PLGA-TPGS random copolymer was synthesized and characterized. DMAB was used to increase retention time at the cell surface, thus increasing the chances of particle uptake and improving oral drug bioavailability. Nanoparticles were found to be of spherical shape with an average particle diameter of around 250 nm. The surface charge of PLGA-TPGS nanoparticles was changed to positive after DMAB modification. The results also showed that the DMAB-modified PLGA-TPGS nanoparticles have significantly higher level of the cellular uptake than that of DMAB-modified PLGA nanoparticles and unmodified PLGA-TPGS nanoparticles. In vitro, cytotoxicity experiment showed advantages of the DMAB-modified PLGA-TPGS nanoparticle formulation over commercial Taxotere® in terms of cytotoxicity against MCF-7 cells. In conclusion, oral chemotherapy by DMAB-modified PLGA-TPGS nanoparticle formulation is an attractive and promising treatment option for patients.

Abstract Background Investigation of global clustering patterns across regions is very important in spatial data analysis. Moran's I is a widely used spatial statistic for detecting global spatial patterns such as an east-west trend or an unusually large cluster. Here, we intend to improve Moran's I for evaluating global clustering patterns by including the weight function in the variance, introducing a population density (PD) weight function in the statistics, and conducting Monte Carlo simulation for testing. We compare our modified Moran's I with Oden's I*pop for simulated data with homogeneous populations. The proposed method is applied to a census tract data set. Methods We present a modified version of Moran's I which includes information about the strength of the neighboring association when estimating the variance for the statistic. We provide a power analysis on Moran's I, a modified version of Moran's I, and I*pop in a simulation study. Data were simulated under two common spatial correlation scenarios of local and global clustering. Results For simulated data with a large cluster pattern, the modified Moran's I has the highest power (43.4%) compared to Moran's I (39.9%) and I*pop (12.4%) when the adjacent weight function is used with 5%, 10%, 15%, 20%, or 30% of the total population as the geographic range for the cluster. For two global clustering patterns, the modified Moran's I (power > 25.3%) performed better than both Moran's I (> 24.6%) and I*pop (> 7.9%) with the adjacent weight function. With the population density weight function, all methods performed equally well. In the real data example, all statistics indicate the existence of a global clustering pattern in a leukemia data set. The modified Moran's I has the lowest p-value (.0014) followed by Moran's I (.0156) and I*pop (.011). Conclusions Our power analysis and simulation study show that the modified Moran's I achieved higher power than Moran's I and I*pop for evaluating global and local clustering patterns on geographic data with homogeneous populations. The inclusion of the PD weight function which in turn redefines the neighbors seems to have a large impact on the power of detecting global clustering patterns. Our methods to improve the original version of Moran's I for homogeneous populations can also be extended to some alternative versions of Moran's I methods developed for heterogeneous populations.

Abstract Background T-cell interferon-gamma release assays (IGRAs) may have a role in the diagnosis of active tuberculosis when evaluating patients for whom standard microbiology has limited sensitivity. Our objective was to examine the accuracy of a commercial IGRA for diagnosis of active tuberculosis in HIV-infected persons. Methods We enrolled HIV-infected patients admitted to Mulago Hospital in Kampala, Uganda with cough ≥ 2 weeks. All patients underwent standard medical evaluation. We collected peripheral blood specimens at enrollment and performed a commercial, ELISPOT-based IGRA according to the manufacturer's recommendations. IGRA sensitivity and specificity were determined using mycobacterial culture results as the reference standard. Results Overall, 236 patients were enrolled. The median CD4+ T-lymphocyte count was 49 cells/μl and 126 (53%) patients were diagnosed with active pulmonary tuberculosis. IGRAs were not performed in 24 (10%) patients due to insufficient mononuclear cell counts. In the remaining 212 patients, results were indeterminate in 54 (25%). IGRAs were positive in 95 of 158 (60%) patients with interpretable results. The proportion of positive test results was similar across CD4+ count strata. IGRA sensitivity was 73% and specificity 54%. IGRA results did not meaningfully alter the probability of active tuberculosis in patients with negative sputum smears. Conclusions An ELISPOT-based IGRA detected a high prevalence of latent tuberculosis infection in a hospitalized population of tuberculosis suspects with advanced HIV/AIDS but had limited utility for diagnosis of active tuberculosis in a high prevalence setting. Further research is needed to identify stronger and more specific immune responses in patients with active tuberculosis.

Abstract Temporal, spatial and space-time scan statistics are commonly used to detect and evaluate the statistical significance of temporal and/or geographical disease clusters, without any prior assumptions on the location, time period or size of those clusters. Scan statistics are mostly used for count data, such as disease incidence or mortality. Sometimes there is an interest in looking for clusters with respect to a continuous variable, such as lead levels in children or low birth weight. For such continuous data, we present a scan statistic where the likelihood is calculated using the the normal probability model. It may also be used for other distributions, while still maintaining the correct alpha level. In an application of the new method, we look for geographical clusters of low birth weight in New York City.

Abstract Background The ability to evaluate geographic heterogeneity of cancer incidence and mortality is important in cancer surveillance. Many statistical methods for evaluating global clustering and local cluster patterns are developed and have been examined by many simulation studies. However, the performance of these methods on two extreme cases (global clustering evaluation and local anomaly (outlier) detection) has not been thoroughly investigated. Methods We compare methods for global clustering evaluation including Tango's Index, Moran's I, and Oden's I*pop; and cluster detection methods such as local Moran's I and SaTScan elliptic version on simulated count data that mimic global clustering patterns and outliers for cancer cases in the continental United States. We examine the power and precision of the selected methods in the purely spatial analysis. We illustrate Tango's MEET and SaTScan elliptic version on a 1987-2004 HIV and a 1950-1969 lung cancer mortality data in the United States. Results For simulated data with outlier patterns, Tango's MEET, Moran's I and I*pop had powers less than 0.2, and SaTScan had powers around 0.97. For simulated data with global clustering patterns, Tango's MEET and I*pop (with 50% of total population as the maximum search window) had powers close to 1. SaTScan had powers around 0.7-0.8 and Moran's I has powers around 0.2-0.3. In the real data example, Tango's MEET indicated the existence of global clustering patterns in both the HIV and lung cancer mortality data. SaTScan found a large cluster for HIV mortality rates, which is consistent with the finding from Tango's MEET. SaTScan also found clusters and outliers in the lung cancer mortality data. Conclusion SaTScan elliptic version is more efficient for outlier detection compared with the other methods evaluated in this article. Tango's MEET and Oden's I*pop perform best in global clustering scenarios among the selected methods. The use of SaTScan for data with global clustering patterns should be used with caution since SatScan may reveal an incorrect spatial pattern even though it has enough power to reject a null hypothesis of homogeneous relative risk. Tango's method should be used for global clustering evaluation instead of SaTScan.

Abstract Background Sputum concentration increases the sensitivity of smear microscopy for the diagnosis of tuberculosis (TB), but few studies have investigated this method in human immunodeficiency virus (HIV)-infected individuals. Methods We performed a prospective, blinded evaluation of direct and concentrated Ziehl-Neelsen smear microscopy on a single early-morning sputum sample in HIV-infected patients with > 2 weeks of cough hospitalized in Kampala, Uganda. Direct and concentrated smear results were compared with results of Lowenstein-Jensen culture. Results Of 279 participants, 170 (61%) had culture-confirmed TB. The sensitivity of direct and concentrated smear microscopy was not significantly different (51% vs. 52%, difference 1%, 95% confidence interval (CI): [-7%, 10%], p = 0.88). However, when results of both direct and concentrated smears were considered together, sensitivity was significantly increased compared with either method alone (64%, 95% CI: [56%, 72%], p < 0.01 for both comparisons) and was similar to that of direct smear results from consecutive (spot and early-morning) specimens (64% vs. 63%, difference 1%, 95% CI: [-6%, 8%], p = 0.85). Among 109 patients with negative cultures, one had a positive direct smear and 12 had positive concentrated smears (specificity 99% vs. 89%, difference 10%, 95% CI: [2%, 18%], p = 0.003). Of these 13 patients, 5 (38%) had improved on TB therapy after two months. Conclusion Sputum concentration did not increase the sensitivity of light microscopy for TB diagnosis in this HIV-infected population. Given the resource requirements for sputum concentration, additional studies using maximal blinding, high-quality direct microscopy, and a rigorous gold standard should be conducted before universally recommending this technique.

Objective: To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children., Methods: A systematic search was conducted in PubMed, Embase, the Cochrane library, Web of Science, China National Knowledge Internet(CNKI), Wanfang Datebase from in ception to February 2022. Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included. Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality, their excellent and good rate of fracture healing, malunion, delayed union or nonunion, infection, limitation of elbow flexion or extension(>10°) were extracted and analyzed using software Rev Man 5.3., Results: A total of 9 retrospective studies involving 647 patients were included, with 255 patients in the screw fixation group(including screw combined with Kirschner wire) and 392 patients in the Kirschner wire fixation group. Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[ OR =0.22, 95% CI (0.09, 0.56), P =0.001]. There were no significant differences between the 2 groups in excellent and good rate of fracture healing, malunion rate( P >0.05). Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[ OR =0.18, 95% CI (0.05, 0.65), P =0.009]., Conclusion: For lateral humeral condyle fractures, Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation. There were no significant differences in the excellent and good rate of fracture healing, malunion. In terms of postoperative efficacy and safety of internal fixation, orthopaedic surgeons are more likely to recommend screws for fixation of lateral humeral condyle fractures in children.

Post-stroke depression is commonly experienced by stroke survivors and has a significant negative impact on the physical, cognitive, and social functioning of those affected. This study aims to investigate the prevalence of depressive symptoms and their associated factors in Chinese stroke patients. Research samples were selected from the China Health and Retirement Longitudinal Study 2018 survey. Depression was evaluated using the 10-item Center for Epidemiological Studies Depression Scale, with a score ≥ 10 defined as depression. Univariate and multivariable analyses were performed to examine the associations of depressive symptoms with demographics, family relationships, health status, and lifestyle. A total of 963 stroke patients were included and 57.8% of them had depressive symptoms. Depressive symptoms were significantly associated with female sex (OR 1.762, 95% CI 1.235-2.514), lower education level (non-formal education: OR 2.148, 95% CI 1.235-3.737, primary to secondary school education: OR 1.964, 95% CI 1.272-3.033), dissatisfaction with spouse (OR 1.912, 95% CI 1.075-3.401), dissatisfaction with life (OR 1.779, 95% CI 1.080-2.931), dissatisfaction with health (OR 1.592, 95% CI 1.138-2.226), pain (OR 1.392, 95% CI 1.005-1.928) and abnormal sleep (OR 1.557, 95% CI 1.126-2.152). The findings suggest the need for regular depression screening and evaluation after a stroke, and that a well-functioning support system, effective health management, and lifestyle modifications could potentially improve the mental state of stroke patients., (© 2024. The Author(s).)

Background: The COVID-19 pandemic's impact on thyroid function is a growing concern. Previous studies have produced inconclusive results, and there is a lack of comprehensive research into the long-term risks of thyroid dysfunction following COVID-19 infection. Methods: In this retrospective cohort study, we used data from the TriNetX international database, which includes electronic health records from a broad, diverse patient population. We compared patients with COVID-19 (cases) to those without (controls), matching for age, sex, race, and comorbidities using propensity score matching. The primary outcome was the diagnosis of thyroid dysfunction (thyrotoxicosis or hypothyroidism) within a 12-month period, analyzed using hazard ratios (HRs) and Kaplan-Meier curves, and stratified by age and sex. Results: Initially, the study included 1,379,311 COVID-19 patients and 6,896,814 non-COVID-19 patients from the TriNetX database. After matching, the cohorts were comparable in demographics and baseline characteristics. This study consistently demonstrated a significant increase in the risk of thyroid dysfunction, including thyrotoxicosis and hypothyroidism, among COVID-19 patients compared to non-COVID-19 patients. In the short term (3 months postexposure), the COVID-19 group exhibited a HR of 2.07 (95% confidence interval [CI] 2.01-2.12) for thyroid dysfunction, which included both thyrotoxicosis (HR 2.10, CI 1.92-2.29) and hypothyroidism (HR 2.08, CI 2.01-2.13). This heightened risk persisted over the long term (up to 12 months), with HRs indicating an ∼2.01-fold increased risk for overall thyroid dysfunction, a 1.8-fold increased risk for thyrotoxicosis, and a 2.04-fold increased risk for hypothyroidism. Subgroup analysis, stratified by age and sex, revealed a notably higher risk of thyroid dysfunction in patients aged 65 and above (HR 2.18, CI 2.11-2.25), compared to those in the under-65 age group (HR 1.97, CI 1.91-2.03). Both male and female patients were associated with an elevated risk, with females showing a slightly higher association with thyroid dysfunction (HR 2.12, CI 2.06-2.16) compared to males (HR 1.76, CI 1.69-1.82). Conclusions: COVID-19 infection was associated with an increased risk of thyroid dysfunction, including thyrotoxicosis and hypothyroidism, regardless of age or sex, during a 12-month follow-up period. Further research is required to validate these findings.

Objective: To explore clinical efficacy of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures by Meta analysis., Methods: Controlled clinical studies on autogenous bone transplantation and bone substitutes in treating tibial plateau fractures published on PubMed,Web of Science,CNKI,Wanfang and other databases from January 2005 to August 2022 were searched by computer. Literature screening and data extraction were performed according to randomized controlled trial(RCT),and the quality of RCT were evaluated by using intervention meta-analysis criteria in Cochrane manual. Meta-analysis of joint depression,secondary collapse rate of articular surface,blood loss,operative time and infection rate between two methods were performed by Rev Man 5.3 software., Results: Seven RCT studies (424 patients) were included,296 patients in bone replacement group and 128 patients in autograft group. Operative time [ MD =-16.79,95% CI (-25.72,-7.85), P =0.000 2] and blood loss[ MD =-70.49,95% CI (-79.34,-61.65), P <0.000 01] between two groups had statistically differences,while joint depression[ MD =-0.17,95% CI (-0.91,0.58), P =0.66],secondary collapse rate of joint surface[ RR =-0.74, 95% CI (0.35,1.57), P =0.43],infection rate [ RR =1.21,95% CI (0.31,4.70), P =0.78] between two groups had no differences., Conclusion: The effects of bone substitute and autograft for the treatment of tibial plateau fracture have similar effects in terms of joint depression,secondary articular surface collapse rate and infection rate. However,compared with autologous bone transplantation,bone replacement could reduce blood loss and shorten operation time.

Local electronic structure engineering is an effective approach for optimizing the catalytic performance of electrocatalysts. Herein, a dual-phase vanadium-doped nickel phosphide (NiV x P) catalyst supported on nickel foam (NF) was synthesized via a successive hydrothermal and phosphorization process with interconnected nanosheet structures and homogeneous distributions. The catalyst's stable phase and strong adhesion to the substrate ensure good electrochemical stability. The incorporation of V effectively promotes initial H 2 O adsorption and H* formation, leading to a lower overpotential. As a result, the fabricated NiV x P@NF demonstrates favorable hydrogen evolution reaction (HER) activity and stability, with only 85 mV overpotential needed to reach 10 mA·cm -2 and showing no significant increase in the overpotential during the long-term 78-hour stability test., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Child maltreatment is a complex problem requiring interdisciplinary collaborative research to generate innovative solutions. The Doris Duke Fellowships for the Promotion of Child Well-Being were designed to identify and nurture emerging scholars committed to child maltreatment prevention and create a supportive interdisciplinary learning network., Objective: This paper examines connectivity within the collaborative network created by the fellowships program using longitudinal social network data., Participants and Setting: Participants were 120 individuals selected as Doris Duke Fellows during their doctoral training at universities in the United States., Methods: Fellows completed annual, voluntary web-based surveys to assess their interactions with other fellows during the past year. Social network analysis methods were used to assess the strength and quality of the learning network over a four-year period., Results: Across four years of data, there were increases in the number of connections, proportion of cross-cohort connections, and proportion of interdisciplinary connections. Network analyses showed a highly connected network consisting of primarily medium- and high-quality connections between fellows from different disciplines. The number of scientific journal articles authored by two or more fellows grew substantially over time., Conclusions: Findings indicate the collaborative network created by the fellowships program is growing and strengthening over time. The new Child Well-Being Research Network extends the fellowships network to a broader group of scholars and professionals to advance diversity, equity, inclusion, and justice in the field of child well-being research., Competing Interests: Conflict of Interest Statement: None to Disclose

Recently, growing evidence of the relationship between G-protein coupled receptor 44 (GPR44) and the inflammation-cancer system has garnered tremendous interest, while the exact role of GPR44 has not been fully elucidated. Currently, there is a strong and urgent need for the development of non-invasive in vivo GPR44 positron emission tomography (PET) radiotracers that can be used to aid the exploration of the relationship between inflammation and tumor biologic behavior. Accordingly, the choosing and radiolabeling of existing GPR44 antagonists containing a fluorine group could serve as a viable method to accelerate PET tracers development for in vivo imaging to this purpose. The present study aims to evaluate published (2000-present) indole-based and cyclopentenyl-indole-based analogues of the GPR44 antagonist to guide the development of fluorine-18 labeled PET tracers that can accurately detect inflammatory processes. The selected analogues contained a crucial fluorine nuclide and were characterized for various properties including binding affinity, selectivity, and pharmacokinetic and metabolic profile. Overall, 26 compounds with favorable to strong binding properties were identified. This review highlights the potential of GPR44 analogues for the development of PET tracers to study inflammation and cancer development and ultimately guide the development of targeted clinical therapies.

Obesity, in which the functional importance of small nucleolar RNAs (snoRNAs) remains elusive, correlates with risk for many cancer types. Here, we identify that the serum copies of adipocyte-expressed SNORD46 correlate with body mass index (BMI), and serum SNORD46 antagonizes interleukin-15 (IL-15) signaling. Mechanically, SNORD46 binds IL-15 via G11, and G11A (a mutation that significantly enhances binding affinity) knockin drives obesity in mice. Functionally, SNORD46 blocks IL-15-induced, FER kinase-dependent phosphorylation of platelet glycoprotein 4 (CD36) and monoglyceride lipase (MGLL) in adipocytes, leading to inhibited lipolysis and browning. In natural killer (NK) cells, SNORD46 suppresses the IL-15-dependent autophagy, leading to reduced viability of obese NK. SNORD46 power inhibitors exhibit anti-obesity effects, concurring with improved viability of obese NK and anti-tumor immunity of CAR-NK cell therapy. Hence, our findings demonstrate the functional importance of snoRNAs in obesity and the utility of snoRNA power inhibitors for antagonizing obesity-associated immune resistance., Competing Interests: Declaration of interests M.A.C. reports grants and personal fees from ImmunoGenesis, Inc. and personal fees from Alligator Bioscience, Inc.; ImmunOS, Inc.; Oncoresponse, Inc.; Nurix, Inc.; Aptevo, Inc.; Kineta, Inc.; Xencor, Inc.; Agenus, Inc.; Adagene, Inc.; and Astrazeneca, Inc. outside the submitted work. K.R. and the University of Texas MD Anderson Cancer Center have an institutional financial conflict of interest with Takeda Pharmaceutical and Affimed GmbH. K.R. participates on the Scientific Advisory Board for GemoAb, AvengeBio, Virogin Biotech, GSK, Caribou Biosciences, Navan Technologies, and Bayer. B.G. is an inventor on patent applications involving targeting ferroptosis in cancer therapy and reports personal fees from Guidepoint Global, Cambridge Solutions, and NGM Bio., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

The regulation of bile acid pathways has become a particularly promising therapeutic strategy for a variety of metabolic disorders, cancers, and diseases. However, the hydrophobicity of bile acids has been an obstacle to clinical efficacy due to off-target effects from rapid drug absorption. In this report, we explored a novel strategy to design new structure fragments based on lithocholic acid (LCA) with improved hydrophilicity by introducing a polar "oxygen atom" into the side chain of LCA, then (i) either retaining the carboxylic acid group or replacing the carboxylic acid group with (ii) a diol group or (iii) a vinyl group. These novel fragments were evaluated using luciferase-based reporter assays and the MTS assay. Compared to LCA, the result revealed that the two lead compounds 1a - 1b were well tolerated in vitro, maintaining similar potency and efficacy to LCA. The MTS assay results indicated that cell viability was not affected by dose dependence (under 25 µM). Additionally, computational model analysis demonstrated that compounds 1a - 1b formed more extensive hydrogen bond networks with Takeda G protein-coupled receptor 5 (TGR5) than LCA. This strategy displayed a potential approach to explore the development of novel endogenous bile acids fragments. Further evaluation on the biological activities of the two lead compounds is ongoing.

Next-generation sequencing has revealed that less than 2% of transcribed genes are translated into proteins, with a large portion transcribed into noncoding RNAs (ncRNAs). Among these, long noncoding RNAs (lncRNAs) represent the largest group and are pervasively transcribed throughout the genome. Dysfunctions in lncRNAs have been found in various diseases, highlighting their potential as therapeutic, diagnostic, and prognostic targets. However, challenges, such as unknown molecular mechanisms and nonspecific immune responses, and issues of drug specificity and delivery present obstacles in translating lncRNAs into clinical applications. In this review, we summarize recent publications that have explored lncRNA functions in human diseases. We also discuss challenges and future directions for developing lncRNA treatments, aiming to bridge the gap between functional studies and clinical potential and inspire further exploration in the field., Competing Interests: Declaration of interests The authors declare no known competing interests., (Copyright © 2023. Published by Elsevier Inc.)

Objective: To compare the long-term follow-up effect and complications of ceramic on ceramic (CoC) interface and ceramic on polyethyleneon ceramic (CoP) interface in primary total hip arthroplasty, and provide clinical evidence., Methods: Search PubMed, EMBase, the CoChrane Library databases, Web of science, Wanfang database, and CNKI from January 2000 to September 2021, screening and inclusion of randomized controlled trials (RCTs) comparing the long-term efficacy and complications of CoC interface and CoP interface in total hip arthroplasty. Literature screening, quality evaluation and data extraction were carried out according to the inclusion and exclusion criteria, using Review Manager 5.3 statistical software. The software was used to perform statistical analysis on joint function, revision, prosthesis fracture, abnormal joint noise, and prosthesis wear rate after CoC or CoP., Results: Seven RCTs studies were included, including 390 cases of hips with CoC artificial joints and 384 cases of hips with CoP artificial joints. The long-term joint function improvement of CoC and CoP artificial joints was similar and there was no significant differences, with an average difference was MD =0.63, 95% CI =(-1.81, 3.07), P =0.61. About the postoperative complications, CoC artificial joints have higher incidence rate of abnormal joint noise, with odds ratio ( OR )=11.05, 95% CI =(2.04, 59.84), P =0.005. CoP artificial joints wear faster, with an average MD =-87.11, 95% CI =(-114.40, -59.82), P <0.000 1. There was no significant difference between the two groups in the replacement-related complications such as joint dislocation, prosthesis loosening, osteolysis, and the rate of prosthesis revision caused by various reasons., Conclusion: The clinical function results and complications of CoC artificial joints are comparable to those of CoP artificial joints. Although CoP artificial joint prosthesis has a faster wear rate, it does not affect joint function and increase complications, and there is no abnormal joint noise. CoC is expensive and the long-term efficacy is equivalent to CoP. Clinicians should consider cost performance when choosing CoC.

Efficient and low-cost transition metal single-atom catalysts (TMSACs) for hydrogen evolution reaction (HER) have been recognized as research hotspots recently with advances in delivering good catalytic activity without noble metals. However, the high-cost complex preparation of TMSACs and insufficient stability limited their practical applications. Herein, a simple top-down pyrolysis approach to obtain P-modified Co SACs loaded on the crosslinked defect-rich carbon nanosheets was introduced for alkaline hydrogen evolution, where Co atoms are locally confined before pyrolysis to prevent aggregation. Thereby, the abundant defects and the unsaturated coordination formed during the pyrolysis significantly improved the stability of the monatomic structure and reduced the reaction barrier. Furthermore, the synergy between cobalt atoms and phosphorus atoms was established to optimize the decomposition process of water molecules, which delivers the key to promoting the slow reaction kinetics of alkaline HER. As the result, the cobalt SAC exhibited excellent catalytic activity and stability for alkaline HER, with overpotentials of 70 mV and 192 mV at current densities of -10 mA cm -2 and -100 mA cm -2 , respectively.

One of the major obstacles to treating pancreatic ductal adenocarcinoma (PDAC) is its immunoresistant microenvironment. The functional importance and molecular mechanisms of Schwann cells in PDAC remains largely elusive. We characterized the gene signature of tumor-associated nonmyelinating Schwann cells (TASc) in PDAC and indicated that the abundance of TASc was correlated with immune suppressive tumor microenvironment and the unfavorable outcome of patients with PDAC. Depletion of pancreatic-specific TASc promoted the tumorigenesis of PDAC tumors. TASc-expressed long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 ( PVT1 ) was triggered by the tumor cell-produced interleukin-6. Mechanistically, PVT1 modulated RAF proto-oncogene serine/threonine protein kinase-mediated phosphorylation of tryptophan 2,3-dioxygenase in TASc, facilitating its enzymatic activities in catalysis of tryptophan to kynurenine. Depletion of TASc-expressed PVT1 suppressed PDAC tumor growth. Furthermore, depletion of TASc using a small-molecule inhibitor effectively sensitized PDAC to immunotherapy, signifying the important roles of TASc in PDAC immune resistance.

Home visitors face the difficult task of engaging and supporting families who experience economic, social, and mental health challenges. Infant and Early Childhood Mental Health Consultation (IECMHC) is one strategy to improve early childhood professionals' abilities to promote maternal and children's mental health through relationship building and collaboration. To date, most of the evidence showing positive effects of IECMHC comes from evaluations conducted in center-based early childhood programs. Only a few have examined the implementation and outcomes of IECMHC in home visiting programs. Using a longitudinal, matched-comparison group design, a three-year pilot study of a cross-system, embedded model of IECMHC assessed implementation and outcomes for teachers and home visitors. Here, we focus on intervention effects on home visitor-family relationships based on an analysis of 42 recordings of home visits. We used the Home Visit Rating Scales Adapted & Extended to Excellence (HOVRS-A+ v.2.1; Roggman et al., in  2010) and created another scale, the IECMHC scale, of items aligned with the expected outcomes of the model. Home visitors in the intervention group scored significantly higher on the HOVRS-A+ home visitor responsiveness to family scale over time than those in the comparison group. Additionally, scores of home visitors in the intervention group increased at a greater rate, on average, on the newly developed IECMHC scale than scores of home visitors in the comparison group. We conclude that the Illinois model of IECMHC successfully improved home visitors' responsiveness to families and improved the quality of home visits. Due to the small sample, we recommend further study of the model in home visiting and further development of the IECMHC scale as part of the HOVRS-A+ ., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)