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Background Along with increasing research on acupuncture for chronic pain, the validity of sham acupuncture (SA) has also been argued. Methods Nine databases were searched for randomized controlled trials (RCTs) from the inception dates of the databases to July 5, 2022. With Markov Chain Monte Carlo methods, a Bayesian multiple-treatment network meta-analysis (NMA) with random-effects model was conducted. Results A total of 62 RCTs with 6,806 patients and four kinds of treatments (real acupuncture [RA], non-acupuncture [NA], penetrative SA [PSA], and non-penetrative SA [NPSA]) were included. The results indicated that both NPSA and PSA were not superior to NA in improving chronic pain (NPSA: mean difference [MD]= –4.77, 95% confidence interval [CI] –11.09 to 1.52; PSA: MD= –4.96, 95% CI –10.38 to 0.48). After NPSA and PSA were combined into the SA group, the weak trend of pain relief from SA was still not statistically significant (MD= –4.91, 95% CI –9.93 to 0.05). NPSA and PSA had similar effects (MD= 0.18, 95% CI –5.45 to 5.81). RA was significantly associated with pain relief, compared with NPSA and PSA (NPSA: MD= –12.03, 95% CI –16.62 to –7.41; PSA: MD= –11.85, 95% CI –15.48 to –8.23). The results were generally consistent regardless of pain phenotype, frequency, duration, acupuncture methods, analgesic intake, or detection bias. Conclusion These results suggested that acupuncture was significantly associated with reduced chronic pain. The two kinds of placebo acupuncture, NPSA and PSA, have similar effects. Both NPSA and PSA, with a weak but not significant effect, are appropriate to be inert placebo controls in RCTs for chronic pain.

This study aimed to assess the clinical characteristics affecting outcomes after immune checkpoint inhibitors (ICI) therapies in non-small cell lung cancer (NSCLC) patients, and the underlying mechanism in tumor immune micro-environment (TIME).A total of 144 patients treated with ICI-based strategies were retrospectively analyzed. Expression of 10 immune antibodies in tumor tissues from other 60 untreated NSCLC patients were sequentially tested using multiplexed immunofluorescence (mIF) staining method. Correlation of clinical characteristics with ICI treatment outcomes and TIME characteristics were analyzed.Multivariate logistic and cox regression indicated that BoM negatively affected disease control rate (OR = 0.32, 95%CI: 0.13-0.82, P = 0.018), progression free survival (HR = 3.44, 95% CI:1.97-6.00, P 0.001) and overall survival (HR = 3.24, 95% CI:1.62-6.50, P = 0.001), irrespective of programmed death-ligand 1 (PD-L1) expression. BoM patients were with significantly lower PD-L1, and this heterogeneity of TIME was then confirmed in the mIF staining, where 36 (61.0%) patients were clustered into immune-subtype A, with low expression of all the detected immune markers, similar to "cold" tumors, and 23 (39.0%) in cluster B with likely "hot" tumors. More patients in immune-subtype A were non-smokers (63.9% vs. 39.1% P = 0.063), with BoM (66.7% vs. 21.7%, P = 0.001), in stage IV(88.9% vs. 65.2%, P = 0.045), and with adenocarcinoma (91.7% vs. 69.6%, P = 0.037). Multivariate logistic regression indicated that BoM was independently associated with the "cold" immune characteristics (OR = 0.19, 95% CI:0.04-0.84, P = 0.028). Combination therapy with chemotherapy /antiangiogenesis or use of bisphosphonate during ICI treatment significantly improved clinical outcomes in BoM patients.BoM displays adverse impact on clinical outcomes after ICI treatments in NSCLC patients. The "cold" characteristics of TIME may be the underlying mechanism for the attenuated efficacy of ICIs in bone metastatic NSCLC patients.

We experimentally investigate the performances of an optical reservoir computing (RC) system based on two parallel time-delay reservoirs composed of two semiconductor lasers (SLs) subject to optical feedback. In such a system, the information being processed is split into two parts to send into two reservoirs through directly modulating the pump currents of two SLs, and the temporal output of the two SLs are sampled and taken as the virtual node states for training and testing. Via Santa Fe time series prediction task and multi-waveform recognition task, the performances of the proposed RC system are investigated and compared with those of the system based on one reservoir. The results show that the system based on two parallel reservoirs behaves better performance and stronger parameter robustness than that based on one reservoir. Moreover, through analyzing the dependence of the system performances on the number of virtual node states actually used for readout, the potential data processing rate (DPR) of the system is evaluated. For processing a prediction task under guaranteeing the normalized mean square error below 0.1 and a recognition task under guaranteeing the signal error rate below 0.005, the potential DPR of the proposed RC system can achieve 200 MSa/s, which is twice the DPR of the system with only one reservoir.

Along with increasing research on acupuncture for chronic pain, the validity of sham acupuncture (SA) has also been argued.Nine databases were searched for randomized controlled trials (RCTs) from the inception date to July 5, 2022. Using Markov Chain Monte Carlo methods, a Bayesian multiple treatment network meta-analysis (NMA) with random-effects model was conducted.A total of 62 RCTs with 6806 patients and four kinds of treatments (real acupuncture (RA), non-acupuncture (NA), penetrative SA (PSA) and non-penetrative SA (NPSA)) were included. The results indicated that both NPSA and PSA were not superior to NA in improving chronic pain (NPSA: MD -4.77 [95% CI, -11.09 to 1.52]; PSA: MD, -4.96 [95% CI, -10.38 to 0.48]). After combining NPSA and PSA into the SA group, the weak trend of pain relief from SA was still not statistically significant (MD, -4.91 [95% CI, -9.93 to 0.05]). NPSA and PSA had similar effects (MD, 0.18 [95% CI, -5.45 to 5.81]). RA was significantly associated with pain relief, compared with NPSA and PSA (NPSA: MD, -12.03 [95% CI, -16.62 to -7.41]; PSA: MD, -11.85 [95% CI, -15.48 to -8.23]). The results were generally consistent regardless of pain phenotype, frequency, duration, acupuncture methods, analgesic intake, or detection bias.These results suggested that acupuncture was significantly associated with reduced chronic pain. The two kinds of placebo acupuncture, NPSA and PSA, have similar effects. Both NPSA and PSA, with a weak but not significant effect, are appropriate to be inert placebo controls in RCTs for chronic pain.

A scheme for generating wideband optical frequency comb (OFC) is proposed and experimentally investigated based on a master-slave system. In such a system, a tunable optical resource and a distributed feedback semiconductor laser are utilized as master lasers (MLs), and their outputs provide dual optical injection (DOI) into a slave laser (SL) which is a 1550 nm multi-transverse mode vertical-cavity surface-emitting laser (1550 nm-VCSEL) operating at gain-switched state. For the 1550 nm-VCSEL biased at a relatively high current, two low-order transverse modes LP01 and LP11 can simultaneously lase and possess comparable powers. After loaded a large signal modulation, the 1550 nm-VCSEL can be driven into gain-switched state, and two separated sub-combs originating from two transverse modes can be generated. Through further introducing DOI to the gain-switched 1550 nm-VCSEL, the two sub-combs can link up to form an overall OFC under suitable operation parameters. The experimental results show that, through selecting optimized operating parameters, the bandwidth of the integral OFC within 10 dB amplitude variation can achieve 150.0 GHz. Additionally, the effects of the wavelengths of the two injection lights on the bandwidth of the overall OFC are also analyzed.

Patients with EGFR gene mutation often obtain de novo resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or develop secondary resistance to EGFR-TKIs after taking EGFR-TKI therapy. Traditional Chinese medicine (TCM) with different treatment principles, in combination with EGFR-TKIs, plays an important role in the treatment of cancers including resistant non-small cell lung cancer (NSCLC). However, inappropriate use of TCM herbs may induce resistance to gefitinib. Therefore, it is of a great value to evaluate which TCM treatment principle should be combined with EGFR-TKIs, and which one should be avoided, and find out the potential mechanisms. The lentiviral transfection assay was used for overexpression of PIK3CA mutation gene in PC-9 cells to construct PC-9-PIK3CA-mutation (PC-9-PIK3CA-M) cells. Cell proliferation, apoptosis, and the expression of EGFR/PI3K/AKT and EGFR/RAS/RAF/ERK in PC-9-PIK3CA-M and H1975 cells treated by the typical cooling-heat drug, Qing-kai-ling (QKL) and Tan-re-qing (TRQ), or the typical warming-yang drug, Shen-fu (SF) and gefitinib treatment, were detected by MTT, Annexin V/PI double labeling, and Western blot assays, respectively. Tumor xenograft and immunohistochemistry experiments were carried out to confirm the in vitro findings. PC-9-PIK3CA-M cells were less sensitive to gefitinib, when compared with PC-9 cells. QKL injection and TRQ injection, not SF injection, combined with gefitinib induced significantly increased cell growth inhibition and apoptosis in PC-9-PIK3CA-M and H1975 cells. SF injection antagonized the effect of gefitinib in promoting cancer cell apoptosis. QKL injection and TRQ injection increased the sensitivity of gefitinib by inhibiting the phosphorylation of AKT or ERK in H1975 and PC-9-PIK3CA-M cells. Similar findings were observed in vivo in H1975 xenograft mouse model. QKL and TRQ, with cooling-heat TCM treatment principle, should be combined with gefitinib in the treatment of NSCLC. Furthermore, warming-yang drug SF should be avoided to be used together with EGFR-TKIs.

Lung cancer organoids (LCOs) have sprung up in more and more researching fields, because of their ability to recapitulate the three-dimensional structure and functions of the in vivo counterpart organs. However, the culture system for LCOs is still immature, resulting in limited success rate and low tumor purity when culturing LCOs. This is mainly due to the deficiency of an optimal formula of culture medium specially for LCOs. Various cytokines and small molecules have been added in the LCOs culturing system. Compound screening, considering both the mechanism of these molecules and the complexity of lung cancer types is warranted to optimize LCOs culture medium. As methods to culture LCOs increase in sophistication, this model will undoubtedly stand its ground in the coming years in every aspect of cancer researches, especially with major advantages in the field of personalized medicine and tumor microenvironment researches.

Based on three-level exciton model, the enhanced photonic microwave signal generation by using a sole excited-state (ES) emitting quantum dot (QD) laser under both optical injection and optical feedback is numerically studied. Within the range of period-one (P1) dynamics caused by the optical injection, the variations of microwave frequency and microwave intensity with the parameters of frequency detuning and injection strength are demonstrated. It is found that the microwave frequency can be continuously tuned by adjusting the injection parameters, and the microwave intensity can be enhanced by changing the injection strength. Moreover, considering that the generated microwave has a wide linewidth, an optical feedback loop is further employed to compress the linewidth, and the effect of feedback parameters on the linewidth is investigated. It is found that with the increase of feedback strength or delay time, the linewidth is evidently decreased due to the locking effect. However, for the relatively large feedback strength or delay time, the linewidth compression effect becomes worse due to the gradually destroyed P1 dynamics. Besides, through optimizing the feedback parameters, the linewidth can be reduced by up to more than one order of magnitude for different microwave frequencies.

Recombinant protein purification remains to be a major challenge in biotechnology and medicine. In this paper we report a simple method for recombinant protein purification using self-assembling peptide-tagged tobacco etch virus protease (TEVp). After construction of an N-terminal ELK16 peptide fusion expression vector, we expressed ELK16-TEVp fusion protein in E. coli. SDS-PAGE analysis showed that ELK16-TEVp was expressed as active protein aggregates which could be purified to 91% purity with 92% recovery by centrifugation in the presence 0.5% Triton X-100. By using His-tagged bovine interferon-γ (His-BoIFN-γ) as the substrate, we demonstrated that EKL16-TEVp had a protease activity of 1.3 × 10(4) units/mg protein with almost 100% cleavage efficiency under the optimized conditions. More importantly, EKL16-TEVp could be removed from the cleavage reaction by single-step centrifugation. After removing the His-tag by nickel-conjugated agarose bead absorption, the recombinant BoIFN-γ (rBoIFN-γ) was purified to 98.3% purity with 63% recovery. The rBoIFN-γ had an antiviral activity of 1.6 × 10(3) units/mg protein against vesicular stomatitis virus. These data suggest that ELK16-TEVp may become a universal tool for recombinant protein purification.

Spectral analysis is a useful tool for the rapid and accurate prediction of soil properties. Our objective is to select the best model for predicting the three soil cation concentrations ([Na+], [Mg2+], and [Ca2+]) and sodium adsorption ratio (SAR). Three methods were applied, i.e., stepwise multiple linear regression (SMLR), partial least-squares regression (PLSR), and support vector machine (SVM). Estimation models for four soil properties were developed using three different spectral processing and transformation techniques, i.e., reflectance (Re), logarithm of reciprocal Re (LR), and standard normal variable of Re (SNV) were used. A total of 36 models were established. Of these, 27 models for [Na+], [Mg2+], and [Ca2+] were not applicable for subsequent prediction, because the coefficients of determination (R2) were not high (0.224–0.689), and their relative percent deviations (RPD) were all smaller than the 1.4 threshold. However, the models for SAR~R using PLSR (R2 = 0.728 for calibration and 0.661 for validation, RPD = 1.43), SAR~LR using SVM (R2 = 0.791 for calibration and 0.712 for validation, RPD = 1.81), and SAR~SNV using SVM (R2 = 0.878 for calibration and 0.814 for validation, RPD = 2.13) were valid for further prediction. Finally, SAR~SNV using SVM was selected as the best model. There are intrinsic factors resulting in an unsatisfied model performance.

Hyperspectral remote sensing data have special advantages, i.e., they have high spectral resolution and strong band continuity, and a great number of spectral information could be widely used in soil properties monitoring research. Using hyperspectral remote sensing technique to analyze saline soil properties makes great significance for the crop growth in the irrigation district and agricultural sustainable development. 221 soil samples were collected from Manasi River Basin to measure soil electrical conductivity (EC), soil organic matter (SOM) and 3 kinds of cation concentrations including Na+, Ca2+ and Mg2+, which were used to obtain sodium adsorption ration value (SAR). The soil hyperspectral curves were also measured. EC, SOM and SAR models were established based on the six spectral-related indices, including raw reflectance (R), standard normal variable (SNV), normalized difference vegetation index (NDVI), logarithm of the reciprocal (LR), the first derivative reflectance (FDR) and continuum-removal reflectance (CR) by the stepwise linear regression method. The results showed that, compared to the other five models, the model of log (EC)~R had the highest accuracy with r value of 0.782 and RMSE value of 0.256. The model of SOM vs. NDVI had the highest accuracy with r value of 0.670 and RMSE value of 5.352. The model of SAR vs. FDR had the highest accuracy with r value of 0.647 and RMSE value of 1.932. As to the model accuracy of the studied soil physico-chemical properties, the log(Ec) model was the most effective one, followed by the SOM model, the SAR model was the most inaccurate. The sensitive wavelengths for EC, SOM and SAR distributed in 395~1 801 nm, 352~1 144 nm and 394~1 011 nm, respectively. Since soil physico-chemical properties were highly spatially variable, there were large differences for the model establishment and validation of the soil properties. This research could be a reference of hyperspectral remote sensing monitoring of salinized soils.

Soil water repellency (SWR) impedes the processes of soil water infiltration and redistribution. Although water repellent soils exist extensively in the world, its causes were not very clear. In this research, three measurement methods including the water droplet penetration time (WDPT), the molarity of ethanol drop (MED) and the contact angle (denoted as θ below) methods, were applied to obtain different SWR indices for the tested soils collected in Manas River Basin, Xinjiang Uygur Autonomous Region, China. The height method and the mass method were conducted to measure θ values. WDPT values of different soil samples were compared to investigate whether WDPT values were affected after being oven-dried or by different bulk densities. The relationships among three SWR indices (WDPT, MED and θ) were compared, and the major soil physico-chemical properties which influenced SWR were analyzed to discuss the intrinsic mechanism that caused SWR. The results showed that WDPT values of higher bulk density were larger than those of lower bulk density, and WDPT values of oven-dried soils were larger than those of air-dried soils. There were correlations between the three SWR indices of WDPT, MED and θ, but MED was insignificantly related to θ, which showed the differences among various SWR indices, although they were related to each other. When measuring θ values of soil-water, θ values obtained using the height method were larger than those obtained using the mass method, and the differences of θ for the three replications with the height method were smaller than those with the mass method. When using octane as the reference liquid for measuring θ values of soil-water, the differences of the three replications were small, being lower than those using ethyl alcohol. Among the studied multi-physico-chemical properties, clay content affected WDPT and θ values more significantly than other soil physico-chemical properties. Concentrations of K土壤斥水性(SWR)阻碍入渗及再分布过程.虽然斥水土壤在世界广泛存在,但其产生机理并不明确.本文采用滴水穿透时间(WDPT)法、酒精摩尔浓度(MED)法和接触角(