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Background. Immune checkpoint inhibitors (ICIs) have changed the situation of tumor therapy in recent years. However, for security reasons, those special populations are often excluded from clinical trials, such as infected hepatitis B or hepatitis C patients. ICIs are systematically reviewed and meta-analyzed for the first time in patients infected with hepatitis B or C in this paper. Methods. The relevant studies were searched in PubMed, EMBASE, Cochrane Library, and Web of Science until October 2022. Trials and observational studies meeting the inclusion criteria were included. The outcomes included the effectiveness of ICIs in patients with HBC/HCV (ORR, DCR, mOS, and mPFS), the incidence of adverse reactions, high-grade adverse reactions, and abnormal liver enzymes. At the same time, these indexes were compared with those of uninfected patients. Results. A total of 2,625 patients were enrolled, involving 1,179 patients with hepatitis (HBV or HCV). We found that ICIs showed higher ORR (25.80% vs. 18.10%) and DCR (66.22% vs. 58.74%) in patients with hepatitis B/C than those without infection. In terms of survival time, patients with hepatitis virus infection showed longer mOS (15.44 m vs. 13.30 m) but shorter mPFS (4.94 m vs. 5.01 m) than uninfected patients. As for safety data, patients with hepatitis showed a lower incidence of all-grade irAEs (68.02% vs. 70.43%) than uninfected patients, while that of 3-4 irAEs (21.27% vs. 21.79%) was similar in the two groups. However, hepatic dysfunction was more common and serious in hepatitis patients. Four HBVr and no HCVr were observed. Conclusion. According to this meta-analysis, ICIs are effective and safe for patients with hepatitis B or C, but basic liver enzymes have to be evaluated before treatment to avoid liver adverse events.

Background Lipid metabolism alternations reprogrammed tumor microenvironment (TME) to participate in clinical response to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC). Body mass index (BMI), clinically used to assess body fat, has been positively correlated with ICIs monotherapy response. Circulating cholesterol is mainly packaged into apolipoproteins B (apoB) in the form of apoB containing lipoproteins, including low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC), which have been regarded as risk factors of tumorigenesis. The association between BMI, lipoproteins, and clinical outcome of ICIs is far from clear. Methods We performed a retrospective case-control analysis of 99 NSCLC patients treated with chemotherapy plus ICIs regimens in the department of oncology and lung cancer center of China-Japan Friendship Hospital between January 2019 to December 2021 and assessed the prognostic value of the BMI, serum lipids, lipoproteins, and apolipoproteins. Efficacy was assessed by response evaluation criteria in solid tumors (RECIST) version 1.1 and evaluated by the ICIs response (durable clinical benefit [DCB] / non-durable benefit [NDB]), best response (active/ non-active) and progression-free survival (PFS). The validation test and the mechanism exploration were performed with public data using bioinformatic methods. Results The contrary results to the ICIs single agents were obtained. BMI ≥ 25 kg/m2 was a risk indicator for NDB, non-active response to ICIs, shorter PFS with the confounders adjusted (OR = 6.06, 95% CI 2.05–19.89, p.val = 0.002; OR = 4.37, 95% CI 1.64–12.43, p.val = 0.004; HR = 3.08, 95% CI 1.63–5.82, p.val 2, the elevated cholesterol-riched apoB containing lipoproteins are promise indicators for the poor ICIs response. Further large-scale validations and experimental explorations are needed.

Developing an efficient approach to decompose ground-level O

Background. Immune checkpoint inhibitors (ICIs) emerge as the first-line treatment of lung adenocarcinoma (LUAD); selection of subpopulations acquiring clinical benefit is required. Associations between epigenetic modulation of tumor microenvironment (TME) and clinical outcome are far from clear. We focused on immune-related genes closely regulated by DNA methylation to identify the potential clinical outcome indicators. Methods. We systematically calculated immunophenotype score (IMpS) and classified immunophenotypes based on seven TME features in three independent cohorts. The overlapping of differential expressed genes and methylated probes targeted genes was regarded as genes closely regulated by DNA methylation. Then, probe/gene pairs which highly correlated with each other and IMpS were identified and named as immune-related probe/gene pairs (mIMg). Prognostic mIMg were selected and verified in seven independent validation cohorts. Results. Three immune phenotypes were clustered, and similar results were obtained in the three independent training cohorts. C2 displayed as an immunologically hot phenotype, whereas C3 corresponded with immunologically cold phenotype. Average methylation level was decreased from C2 to C3 (C2 > C1 > C3). Similarly, ICIs nonresponders showed global hypo-methylation compared with responders. Genes in mIMg were mainly enriched, especially in T-cell receptor activation, and repressed in noninflamed TME by hyper-methylation. Among mIMg, low expression and hyper-methylation of CD247, LCK, and PSTPIP1 were risk factors of overall survival (OS). ICIs nonresponders were more likely to be hyper-methylated in the three genes. By integrating with the oncogenes status, we demonstrated that EGFR wt and SRGN overexpressed patients were associated with chronic inflammation and immune evasion, showing an immunologically hot phenotype, which might lead to the short OS but derive clinical benefit from ICIs. Conclusions. This study identifies hyper-methylation and concurrent repression of CD247, LCK, PSTPIP1 as immune negative indicators and risk factors for prognosis in LUAD. Moreover, EGFR/SRGN axis may participate in immune modification to influence ICIs response and clinical outcome in LUAD.

Immune checkpoint inhibitors (ICIs) have changed the status of tumor immunotherapy. ICIs-related adverse events (irAEs) have the high incidence and are difficult to predict and prevent. Researches have suggested that changes of cytokines were associated with irAEs. This study focused on the changes of interleukin-6 (IL-6) and interferon-γ in patients before and after irAEs and trying to find the biomarkers of irAEs. Collect basic data of patients who were treated with ICIs in China-Japan Friendship Hospital from January 2017 to August 2021 and had irAEs. Make statistics on IL-6 and INF-γ in the blood before and after irAEs. A total of 10 patients were enrolled, including 7 males and 3 females. According to statistical analysis, the IL-6 concentration level after irAEs was significantly higher than before, and the difference was statistically significant (P = .023); the interferon-γ concentration level was not changed significantly from before, the difference was not statistically significant (P = .853). The elevation of IL-6 was associated with the occurrence of adverse reactions in ICIs.

Mechanical wear failure is the main cause of device failure, and wear particles can be utilized to judge the degree and mechanism of mechanical wear. However, with the further study by researchers, the classes of wear particles are likely to increase. As the number of classes increases, it is necessary to reconstruct and retrain the previous automatic recognition model of wear particles. To solve this problem, a novel convolutional neural network (CNN) model based on class center vectors and distance comparison, called CDCNN, is proposed in this study. The model can not only accurately classify the particles that appear in the training set, but also identify the new classes that were not seen during training. This work can show its advantages when the classification criteria for wear particles have changed or new classes of particles have appeared. We applied the proposed model and the previous convolutional neural network model for the wear particle dataset, and compared the classification results of the models. The comparison results show that the model has strong classification ability and generalization ability.

The accumulation of antibiotics in river watersheds and lakes could induce the spread of antibiotic-resistance genes in drinking water, causing damage to human health. An OH equipment, that produces OH by strong ionization discharge combined with water jet cavitation effect, was installed in a drinking water treatment system of 12,000 m3 per day in Xiang’an water plant, Xiamen of China. The NFX as a model antibiotic was mixed into a branched pipe at a flow rate of 1.0 m3 h−1 for OH mineralization. As a result, the OH after coagulation sedimentation at 1.0 mg L−1 and after sand filtration at 0.5 mg L−1 degraded NFX to not detected within only 20 s. Moreover, the OH mineralizes the NFX into CO2 and H2O by breaking the C F bond, and opening the piperizine, nalidixic, and benzene rings, while NaClO only opens the piperizine ring and adversely forms chlorinated intermediates. By OH disinfection at 0.5 mg L−1 in the main pipe of 500 m3 h−1, all algae blooms were inactivated; the tests of 106 drinking water quality indicators satisfied the Chinese Standards; any disinfection by-products, such as bromate and trihalomethanes (THMs) were not be detected. By NaClO disinfection, the total THMs increased to 190 μg L−1, which is 2.4 times higher than the limit regulated by Environmental Protection Agency (80 μg L−1). To prevent the spread of antibiotic-resistance genes in humans, OH advanced oxidation based on strong ionization discharge could be apply to mineralize antibiotics during practical drinking water treatment.

e21036 Background: Non-small cell lung cancer(NSCLC) patients(pts) with epidermal growth factor receptor (EGFR) exon 19 deletion have more benefit from EGFR-tyrosine kinase inhibitors(EGFR-TKIs) compared to pts with EGFR exon 21 L858R mutation. Icotinib, which is a first-generation EGFR-TKI had been approved for use in EGFR-positive advanced NSCLC pts. A phase II trial(INCREASE trial) showed that high-dose icotinib 250mg tid(ico250) can effectively prolong the progression-free survival(PFS) of NSCLC pts with exon 21 L858R mutation without increased toxicity. However, the RW evidence is lacking. Methods: In this single-center, single-arm study, data were retrospectively collected from China-Japan Friendship Hospital. Pts with advanced LUAD, harboring EGFR exon 21 L858R mutation, and who received ico250 for more than 20 days without chemotherapy or immunotherapy were reviewed. Clinical data were analyzed for PFS, objective response rate(ORR), disease control rate(DCR), overall survival(OS), duration of treatment(DoT) and adverse events(AEs). Survival factors were evaluated by univariate and multivariate Cox regression analysis. Results: In total 40 pts(14M,26F; median age 67[46-86]; smoker:20.0%; ECOG performance status 0-1/2-3: 33/7) who received ico250 between 4/2019-11/2021 were analyzed. The median line of pre-ico therapies was 1(range 0-2). At the cut-off day, 29(72.5%) pts had discontinued ico250, and 7(17.5%) pts died. Overall, ORR was 30.0%, DCR was 80.0%, median DoT was 8.0mos (95%CI, 3.4-12.6), median PFS was 12.9mos (95%CI, 8.2-17.6) and median OS was not reached. The univariate and multivariate analysis showed that there was no significant and independent factor associated with PFS(all P> 0.05). 30(75.0%) pts experienced AEs, while the most common AEs were rash(24,60.0%), dry skin(9,22.5%), paronychia(8,20.0%) and diarrhea(6,15.0%). Grade 3/4 AEs in 6(15.0%) pts included AST/ALT elevation(3,7.5%), rash(2,5%), diarrhea(1,2.5%) and mucositis(1,2.5%)(1 suffered both rash and mucositis). 5(12.5%) pts discontinued high-dose icotinib due to AEs. Conclusions: These data add to the RW evidence that the efficacy and tolerability of ico250 in advanced LUAD pts harboring EGFR exon 21 L858R mutation. The efficacy results are consistent with the previous INCREASE trial. High-dose icotinib could be considered whatever the previous treatment and basic characteristics of LUAD pts with exon 21 L858R mutation. However, the higher incidence of grade3/4 AEs deserves special attention.

Biomedical degradable polyester materials are widely used in medical field because of their excellent mechanical properties and degradation properties. Analysis of the degradation process and strength change of biomedical degradable materials is essential for clinical use. The evolution of structure from micro to mesoscale is critical for chain broken, recrystallization and macro strength performance during polymer degradation. A structure pattern dynamic interaction method coupled with multi-scale model is proposed in this paper to simulate the degradation process. In the process of status evolution, Blocked Cavity structure pattern (BC pattern) and Blocked Amorphous pattern (BA pattern) are denoted as the interaction of different phases due to their influence on chain scission and oligomer diffusion. In strength structure, Crystalline Island pattern, Amorphous Island pattern and Vacancy Marsh pattern are defined as the interaction to model the strength support. An algorithm named Boundary Encirclement Algorithm (BEA) is designed for the interaction pattern recognition. With the evolution of different phase patterns and the interaction of different phases, chain broken, recrystallization and oligomer diffusion are reconsidered in local area. And strength model is constructed which is based on the interaction of strength patterns. The coupled multiscale model is denoted as Structure Dynamic Interaction-Multiscale Degradation Model (SDI-MSDM). Calculated examples are compared with the experimental data. The simulation value and the experimental value are well fitted, which indicates that the patterns recognition affect the model calculation.

Photoluminescence (PL) spectra were measured for dodecene-capped Si nanocrystals with a wide range of average diameters, from 1.8 to 9.1 nm. Nanocrystals larger than 3 nm exhibited relatively high PL quantum yields of 30%−45%. Smaller nanocrystals exhibited lower quantum yields that decreased significantly with reduced size. Because smaller nanocrystals also have lower optical absorption there is a significant biasing of the PL spectra by the larger nanocrystals. We show that with proper accounting of polydispersity and size- dependent quantum yields and optical absorption the effective mass approximation (EMA) accurately estimates the average diameter of silicon (Si) nanocrystals from experimentally determined PL emission peak energies. A finite confinement model is presented that explains the decreased PL quantum yields of the smaller diameter nanocrystals.

Nanocrystal superlattices are typically fabricated by either solvent evaporation or destabilization methods that require long time periods to generate highly ordered structures. In this paper, we report for the first time the use of electric fields to reversibly drive nanocrystal assembly into superlattices without changing solvent volume or composition, and show that this method only takes 20 min to produce polyhedral colloidal crystals, which would otherwise need days or weeks. This method offers a way to control the lattice constants and degree of preferential orientation for superlattices and can suppress the uniaxial superlattice contraction associated with solvent evaporation. In situ small-angle X-ray scattering experiments indicated that nanocrystal superlattices were formed while solvated, not during drying.

The growth of algae in water and the taste and odour compounds produced by algal metabolism present a threat to water quality, public health and aquatic ecosystems and cannot be effectively removed by conventional water treatment processes. In this paper, a hydroxyl radical (OH)-based drinking water treatment system (DWTS) with a capacity of 480 m

We recently observed that a disordered assembly of octadecanethiol-capped gold (Au) nanocrystals can order when heated from room temperature to 60 °C [Yu, Y.; Jain, A.; Guillaussier, A.; Voggu, V. R.; Truskett, T. M.; Smilgies, D.-M.; Korgel, B. A. Faraday Discuss. 2015, 181, 181–192]. This “inverse melting” structural transition was reversible and occurred near the melting-solidification temperature of the capping ligands. To determine the generality of this phenomenon, we studied by in situ grazing incidence small-angle X-ray scattering (GISAXS) the structure of assemblies of Au nanocrystals with shorter C12 and C5 alkanethiol capping ligands that form ordered superlattices at room temperature and have a ligand melting-solidification temperature below room temperature. Superlattices of dodecanethiol-capped Au nanocrystals disorder when cooled below 260 K, which is the melting-solidification temperature for dodecanethiol. Au nanocrystals capped with even shorter pentanethiol ligands that have a melting t...

Plastic photovoltaic devices (PVs) were fabricated by spray-depositing copper indium diselenide (CuInSe2) nanocrystals into micrometer-scale groove features patterned into polyethylene terephthalate (PET) substrates. Each groove has sidewall coatings of Al/CdS and Au and performs as an individual solar cell. These PV groove features can be linked electrically in series to achieve high voltages. For example, cascades of up to 15 grooves have been made with open-circuit voltages of up to 5.8 V. On the basis of the groove geometry, the power conversion efficiencies (PCEs) of the devices reached as high as 2.2%. Using the active area and photovoltaic response of devices determined from light-beam-induced current (LBIC) and photoreflectivity measurements gave PCE values as high as 4.4%.

Biomedical degradable polymer materials are widely used in medicine because of their excellent mechanical properties and degradation properties. The matching of strength change and degradation rate in the degradation process is a crucial consideration in the design of polymer devices. Establishing a strength model of the polymer degradation process can quantify the intensity evolution during the degradation process. In this research, the structural changes in the process of polymer erosion degradation are taken as the primary consideration, and the evolution of the phases of strength are reflected by the changes of structure. The concept of strength phase images is proposed. The images of the strength phase diagram are identified by the image processing method. The Near Neighbor-Boundary Enlargement Algorithm (NNBE) is put forward to identify features with the hole(block) and crack(strip) shape patterns. The strength model for different phase patterns is established. The model calculation is compared with the experimental data, and the model simulation value and the experimental value are well fitted, which indicates that the strength model and phase diagram feature extraction algorithm are feasible.

This paper addresses the assembly of body centered-cubic (bcc) superlattices of organic ligand-coated nanocrystals. First, examples of bcc superlattices of dodecanethiol-capped Au nanocrystals and oleic acid-capped PbS and PbSe nanocrystals are presented and examined by transmission electron microscopy (TEM) and grazing incidence small-angle X-ray scattering (GISAXS). These superlattices tend to orient on their densest (110) superlattice planes and exhibit a significant amount of {112} twinning. The same nanocrystals deposit as monolayers with hexagonal packing, and these thin films can coexist with thicker bcc superlattice layers, even though there is no hexagonal plane in a bcc lattice. Both the preference of bcc in bulk films over the denser face-centered cubic (fcc) superlattice structure and the transition to hexagonal monolayers can be rationalized in terms of packing frustration of the ligands. A model is presented to calculate the difference in entropy associated with capping ligand packing frustration in bcc and fcc superlattices.

Dodecanethiol-capped gold (Au) nanocrystal superlattices can undergo a surprisingly diverse series of ordered structure transitions when heated (Goodfellow, B. W.; Rasch, M. R.; Hessel, C. M.; Patel, R. N.; Smilgies, D.-M.; Korgel, B. A. Nano Lett. 2013, 13, 5710-5714). These are the result of highly uniform changes in nanocrystal size, which subsequently force a spontaneous rearrangement of superlattice structure. Here, we show that halide-containing surfactants play an essential role in these transitions. In the absence of any halide-containing surfactant, superlattices of dodecanethiol-capped (1.9-nm-diameter) Au nanocrystals do not change size until reaching about 190-205 °C, at which point the gold cores coalesce. In the presence of halide-containing surfactant, such as tetraoctylphosphonium bromide (TOPB) or tetraoctylammounium bromide (TOAB), the nanocrystals ripen at much lower temperature and superlattices undergo various ordered structure transitions upon heating. Chloride- and iodide-containing surfactants induce similar behavior, destabilizing the Au-thiol bond and reducing the thermal stability of the nanocrystals.

Undecanoic acid facilitates attachment of styrene to hydride-terminated Si nanocrystals at room temperature, avoiding polymerization of styrene, yielding free-standing styrene-terminated Si nanocrystals. The nanocrystals have diamond cubic crystal structure, with photophysical properties similar to typical alkene-capped Si nanocrystals, such as bright photoluminescence with relatively long radiative lifetimes. We propose a reaction mechanism for room temperature styrene addition in which the resonance form of undecanoic acid coordinates to surface Si-H and facilitates H(-) attack at terminal C═C of styrene.

Two families of strongly luminescent silicon nanocrystals (SiNCs) cofunctionalized with dodecyl chains and pyrene chromophores perform as light-harvesting antennae and interact with carbon allotropes. The energy harvested in the SiNC core can thus be used to populate, for example, the lowest triplet excited state of C-60.

A method was developed to create free-standing nanocrystal films in the form of solidified bubbles. Bubbles of octadecanethiol-capped gold nanocrystals were studied by in situ grazing incidence small-angle X-ray scattering (GISAXS) to determine how the absence of an underlying substrate influences a disorder–order transition of a nanocrystal superlattice. We find that the presence of the substrate does not significantly change the nature of the disorder–order transition but does lead to reduced interparticle separation and reduced thermal expansion. Bubble assemblies of silicon and copper selenide nanocrystals are also demonstrated.

Auger recombination lifetimes, absorption cross sections, and the quantum yields of carrier multiplication (CM), or multiexciton generation (MEG), were determined for solvent-dispersed silicon (Si) nanorods using transient absorption spectroscopy (TAS). Nanorods with an average diameter of 7.5 nm and aspect ratios of 6.1, 19.3, and 33.2 were examined. Colloidal Si nanocrystals of similar diameters were also studied for comparison. The nanocrystals and nanorods were passivated with organic ligands by hydrosilylation to prevent surface oxidation and limit the effects of surface trapping of photoexcited carriers. All samples used in the study exhibited relatively efficient photoluminescence. The Auger lifetimes increased with nanorod length, and the nanorods exhibited higher CM quantum yield and efficiency than the nanocrystals with a similar band gap energy Eg. Beyond a critical length, the CM quantum yield decreases. Nanorods with the aspect ratio of 19.3 had the highest CM quantum yield of 1.6 ± 0.2 at 2....

While silicon nanostructures are extensively used in electronics, the indirect bandgap of silicon poses challenges for optoelectronic applications like photovoltaics and light emitting diodes (LEDs). Here, we show that size-dependent pseudo-direct bandgap transitions in silicon nanocrystals dominate the interactions between (photoexcited) charge carriers and phonons, and hence the optoelectronic properties of silicon nanocrystals. Direct measurements of the electronic density of states (DOS) for different sized silicon nanocrystals reveal that these pseudo-direct transitions, likely arising from the nanocrystal surface, can couple with the quantum-confined silicon states. Moreover, we demonstrate that since these transitions determine the interactions of charge carriers with phonons, they change the light emission, absorption, charge carrier diffusion and phonon drag (Seebeck coefficient) in nanoscaled silicon semiconductors. Therefore, these results can have important implications for the design of optoelectronics and thermoelectric devices based on nanostructured silicon.