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Abstract Background We conducted a systematic review and meta-analysis to assess the risk of respiratory adverse effects in patients with solid tumors treated with immune checkpoint inhibitors (PD-1, PD-L1 and CTLA-4 inhibitors) in combination with radiation therapy. Methods We selected eligible studies through the following databases: PubMed, Embase, Cochrane Library, and Clinicaltrials ( https://clinicaltrials.gov/ ). The data was analyzed by using Rstudio. Results Among 3737 studies, 26 clinical trials, including 2670 patients, were qualified for the meta-analysis. We evaluated the incidence rates of adverse respiratory events, including cough, pneumonia, upper respiratory tract infections, and others: grades 1–5 cough, 0.176 (95%CI: 0.113–0.274, I2 = 92.36%); grades 1–5 pneumonitis, 0.118 (95%CI: 0.067–0.198, I2 = 88.64%); grades 1–5 upper respiratory tract infection, 0.064 (95%CI: 0.049–0.080, I2 = 0.98%); grades 3–5 cough, 0.050 (95%CI: 0.012–0.204, I2 = 8.90%); grades 3–5 pneumonitis, 0.052 (95%CI: 0.031–0.078, I2 = 83.86%); grades 3–5 upper respiratory tract infection, 0.040 (95%CI: 0.007–0.249, I2 = 45.31%). Conclusions Our meta-analysis demonstrated that ICI combined with radiotherapy for solid tumors can produce respiratory adverse effects. ICIs combination treatment, a tumor located in the chest, is more likely to cause adverse reactions, and SBRT treatment and synchronous treatment will bring less incidence of adverse reactions. This study provide insights for clinicians to balance the risks of radiotherapy in the course of treating oncology patients.

Abstract The underlying atomistic mechanism of deformation is a central problem in mechanics and materials science. Whereas deformation of crystalline metals is fundamentally understood, the understanding of deformation of amorphous metals lacks behind, particularly identifying the involved temporal and spatial scales. Here, we reveal that at small scales the size-dependent deformation behavior of amorphous metals significantly deviates from homogeneous flow, exhibiting increasing deformation rate with reducing size and gradually shifted composition. This transition suggests the deformation mechanism changes from collective atomic transport by viscous flow to individual atomic transport through interface diffusion. The critical length scale of the transition is temperature dependent, exhibiting a maximum at the glass transition. While viscous flow does not discriminate among alloy constituents, diffusion does and the constituent element with higher diffusivity deforms faster. Our findings yield insights into nano-mechanics and glass physics and may suggest alternative processing methods to epitaxially grow metallic glasses.

In metallic liquids, the fragility is difficult to predict and measure. Here, the authors present the film inflation method, which reveals large fragility variations across Mg–Cu–Y, and introduce the crystallization complexity as additional contribution to glass forming ability.

Abstract Aims/Introduction Non‐alcoholic fatty liver disease and type 2 diabetes mellitus are closely related, and often occur simultaneously in patients. Type 2 diabetes increases the risk of diabetic peripheral neuropathy, resulting in intolerable pain and extremity amputation that reduces the quality of life. However, the role of non‐alcoholic fatty liver disease in the pathogenesis of diabetic peripheral neuropathy remains unclear. Thus, we evaluated the correlation of liver fibrosis and steatosis, which are representative histological morphologies of non‐alcoholic fatty liver disease, with diabetic peripheral neuropathy in type 2 diabetes patients. Materials and Methods Five hundred twenty individuals with type 2 diabetes were recruited. All the patients were detected nerve conduction study for diabetic peripheral neuropathy and fibro touch for liver steatosis and fibrosis. Correlation of DPN with liver steatosis and fibrosis were analysed with binary logistic analysis. Results Among the 520 patients, the prevalence of liver steatosis, fibrosis and diabetic peripheral neuropathy was 63.0% (n = 328), 18.1% (n = 94) and 52.1% (n = 271), respectively. The prevalence of diabetic peripheral neuropathy was significantly elevated in patients with liver steatosis (55.7 vs 44.9%, P = 0.03) and fibrosis (61.5 vs 50%, P = 0.04), and it increased as liver stiffness measurement increased. Additionally, both hepatic steatosis (odds ratio 1.48, 95% confidence interval 1.04–2.11, P = 0.03) and fibrosis (odds ratio 1.60, 95% confidence interval 1.02–2.51, P = 0.04) were correlated with diabetic peripheral neuropathy. After adjusting for age, sex, weight, height, body mass index, waist hip ratio, duration of type 2 diabetes, blood glucose, homeostatic model assessment of insulin resistance, blood pressure, serum lipid, liver enzyme, urea, uric acid, creatinine and inflammatory factors, liver fibrosis remained associated with diabetic peripheral neuropathy (odds ratio 2.24, 95% confidence interval 1.11–4.53, P = 0.02). Conclusions The prevalence of diabetic peripheral neuropathy was elevated in patients with liver steatosis and fibrosis. Liver fibrosis was also independently associated with an increased risk of diabetic peripheral neuropathy.

Abstract Background The TM4 (UBAC2) protein, which contains 4 transmembrane domains and one ubiquitin binding domain, is mainly expressed in cell and nuclear membranes. The current research aimed to explore the role of TM4 in metabolic inflammation and to examine whether the ubiquitin–proteasome inhibitor PS-341 could regulate the function of TM4. Methods The metabolic phenotypes of TM4 knockout (KO) mice were studied. We next explored the association between the polymorphisms of TM4 and obesity in a Chinese Han population. TM4 expression in the visceral fat of obese patients who underwent laparoscopic cholecystectomy was also analysed. Finally, the effect of PS-341 on the degradation and function of the TM4 protein was investigated in vivo and in vitro. Results TM4 KO mice developed obesity, hepatosteatosis, hypertension, and glucose intolerance under a high-fat diet. TM4 counterregulated Nur77, IKKβ, and NF-kB both in vivo and in vitro. The TM4 SNP rs147851454 is significantly associated with obesity after adjusting for age and sex (OR 1.606, 95% CI 1.065–2.422 P = 0.023) in 3394 non-diabetic and 1862 type 2 diabetic adults of Han Chinese. TM4 was significantly downregulated in the visceral fat of obese patients. PS-341 induced TM4 expression through inhibition of TM4 degradation in vitro. In db/db mice, PS-341 administration led to downregulation of Nur77/IKKβ/NF-κB expression in visceral fat and liver, and alleviation of hyperglycaemia, hypertension, and glucose intolerance. The hyperinsulinaemic-euglycaemic clamp demonstrated that PS-341 improved the glucose infusion rate and alleviated insulin resistance in db/db mice. Conclusions PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through inhibition of TM4 degradation.

Abstract Direct measurement of critical cooling rates has been challenging and only determined for a minute fraction of the reported metallic glass forming alloys. Here, we report a method that directly measures critical cooling rate of thin film metallic glass forming alloys in a combinatorial fashion. Based on a universal heating architecture using indirect laser heating and a microstructure analysis this method offers itself as a rapid screening technique to quantify glass forming ability. We use this method to identify glass forming alloys and study the composition effect on the critical cooling rate in the Al–Ni–Ge system where we identified Al51Ge35Ni14 as the best glass forming composition with a critical cooling rate of 104 K/s.

In electromagnetic sounding, the detection areas of time-domain and frequency-domain electromagnetic detection methods cannot be effectively connected, and the detection processes for these two methods must be implemented separately. To combine time-domain and frequency-domain electromagnetic detection methods and simplify the detection process, a time-frequency fusion transmission method is proposed to simultaneously excite the earth to produce transient and steady-state responses. By analyzing the characteristics of the time-domain and frequency-domain excitation current waveforms, a pseudorandom transmission waveform with dead time is designed, and a transmission system for a time-frequency fusion electromagnetic detection method is developed. In this detection mode, the pseudorandom transmission waveform contains several frequencies, and the transient induction field can be received during the dead time. The time-domain and frequency-domain responses can be obtained by the same procedure. At the same time, a self-adaptive pseudoload device is designed and matched with the corresponding control sequence to reduce the influence of dead-time. The experimental results show that the self-adaptive pseudoload transmitter can effectively reduce the current fluctuation, and the time-frequency electromagnetic transmission system can effectively excite the earth to produce transient and steady-state responses. The time-frequency fusion electromagnetic transmission method proposed in this paper can be used in electromagnetic detection instruments to improve the efficiency of electromagnetic sounding.

Background/Aims: Non-small-cell lung carcinoma (NSCLC) is the leading cause of cancer death, with tumor metastasis being mainly responsible for lung cancer-associated mortality. Our previous studies have found that tubulin polymerization promoting protein family member 3 (TPPP3) acted as a potential oncogene in NSCLC. Little is known about the function of TPPP3 in tumor metastasis. Methods: RT-qPCR and IHC were used to investigate the expression of TPPP3 in NSCLC tissues. CCK8 assay and transwell assay were used to measure proliferation and migration of NSCLC cells in vitro and xenograft model was performed to assess the tumor growth and metastasis in vivo. Results: In the present study, upregulation of TPPP3 was found to correlate with an increased metastasis capability of NSCLC. Ectopic expression of TPPP3 significantly enhanced cell proliferation in vitro and promoted tumor growth in vivo. Furthermore, overexpression of TPPP3 remarkably promoted NSCLC cell migration and invasion along with the upregulation of Twist1 both in vitro and in vivo. Further investigations showed that activation of STAT3 was required for TPPP3-mediated upregulation of Twist1, cell migration and invasion. A strong positive correlation between TPPP3 and Twist1 expression was identified in NSCLC tissues. Patients with low TPPP3 or low Twist1 in NSCLC tissues had a better prognosis with longer overall survival (OS) and disease-free survival (DFS). Conclusion: Overall, this study demonstrates that TPPP3 promotes the metastasis of NSCLC through the STAT3/Twist1 pathway.

Monitoring homeostasis is an essential aspect of obtaining pathophysiological insights for treating patients. Accurate, timely assessments of homeostatic dysregulation in deep tissues typically require expensive imaging techniques or invasive biopsies. We introduce a bioresorbable shape-adaptive materials structure that enables real-time monitoring of deep-tissue homeostasis using conventional ultrasound instruments. Collections of small bioresorbable metal disks distributed within thin, pH-responsive hydrogels, deployed by surgical implantation or syringe injection, allow ultrasound-based measurements of spatiotemporal changes in pH for early assessments of anastomotic leaks after gastrointestinal surgeries, and their bioresorption after a recovery period eliminates the need for surgical extraction. Demonstrations in small and large animal models illustrate capabilities in monitoring leakage from the small intestine, the stomach, and the pancreas. [ABSTRACT FROM AUTHOR]

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Large-scale, controlled fabrication of ordered phases is challenging at the nanoscale, yet highly demanded as their well-ordered structure and chemistry is the key for advanced functionality. Here, we demonstrate a general nanomolding process of ordered phases based on atomic diffusion. Resulting nanowires are single crystals and maintain their composition and structure throughout their length, which we explain by a self-ordering process originating from their narrow Gibbs free energy. The versatility, control, and precision of this thermomechanical nanomolding method of ordered phases provides new insights into single crystal growth and suggest itself as a technology to enable wide spread usage for nanoscale and quantum devices. [ABSTRACT FROM AUTHOR]

We report on a thermomechanical nanomolding method for crystalline metals. Quantified by the aspect ratio, this process becomes easier with decreasing mold diameter. As the responsible underlying diffusion mechanism is present in all metals and alloys, the discovered nanomolding process provides a toolbox to shape essentially any metal and alloy into a nanofeature. Technologically, this highly versatile and practical thermomechanical nanomolding technique offers a method to fabricate high-surface-area metallic nanostructures which are impactful in diverse fields of applications including catalysts, sensors, photovoltaics, microelectronics, and plasmonics. [ABSTRACT FROM AUTHOR]