Pulmonary lymphoepithelioma‐like carcinoma (PLELC) is a rare and histologically distinctive subtype of nonsmall cell lung cancer (NSCLC). High expression of programmed death ligand 1 (PD‐L1) and ...scarcity of druggable driver mutations raise the potential of immunotherapy for advanced PELEC. However, evidence on the clinical impact of immune‐checkpoint inhibitors (ICIs) remained limited and unconvincing. The present study retrospectively enrolled advanced PLELC patients who received ICIs either as up‐front or salvage therapy in SYSUCC between March 15, 2017 and March 15, 2022. The comparative efficacy of chemoimmunotherapy vs chemotherapy in the first‐line setting and chemoimmunotherapy vs ICIs monotherapy in the ≥2 line setting was investigated. A total of 96 patients were finally enrolled; 49 PLELC patients received immunotherapy plus platinum‐based chemotherapy, while 45 patients received platinum‐based chemotherapy as first‐line treatment. Patients with chemoimmunotherapy significantly obtain more survival benefits than those receiving chemotherapy (median progression‐free survival PFS: 15.6 vs 8.6 months, P = .0015). Additionally, patients with chemoimmunotherapy obtained more PFS benefits than those with ICIs monotherapy in the ≥2 line of therapy (median PFS: 21.7 months vs 7.8 months, P = .094). A significant correlation was observed between prognostic nutritional index (PNI) and favorable treatment outcomes in patients receiving first‐line chemoimmunotherapy (median PFS: 17.8 months vs 7.6 months, P < .0001). Likewise, patients in the monocyte‐to‐lymphocyte ratio (MLR)‐high group had significantly shorter PFS than the MLR‐low group (median PFS: 11.2 months vs not reached, P = .0009). Our study elucidated the superior efficacy of ICIs therapy, especially chemoimmunotherapy in advanced PLELC, which may provide new insight into the role of immunotherapy in advanced PLELC.
What's new?
The high expression of PD‐L1 and scarcity of druggable driver mutations raise the potential of immunotherapy in treating advanced pulmonary lymphoepithelioma‐like carcinoma. However, evidence on the clinical impact of immune checkpoint inhibitors remains limited. Our study shows that patients receiving first‐line chemoimmunotherapy obtain more survival benefits than patients receiving traditional chemotherapy. Chemoimmunotherapy also shows a favorable treatment outcome compared to immune checkpoint inhibitors monotherapy after progression on first‐line platinum‐based chemotherapy. Moreover, the study supports the potential of the pretreatment serum prognostic nutritional index and monocyte‐to‐lymphocyte ratio as prognostic markers for immunotherapy in advanced pulmonary lymphoepithelioma‐like carcinoma.
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Fluorescent probes have emerged as indispensable chemical tools to the field of chemical biology and medicine. The ability to detect intracellular species and monitor physiological ...processes has not only advanced our knowledge in biology but has provided new approaches towards disease diagnosis. In this review, we detail the design criteria and strategies for some recently reported fluorescent probes that can detect a wide range of biologically important species in cells and in vivo. In doing so, we highlight the importance of each biological species and their role in biological systems and for disease progression. We then discuss the current problems and challenges of existing technologies and provide our perspective on the future directions of the research area. Overall, we hope this review will provide inspiration for researchers and prove as useful guide for the development of the next generation of fluorescent probes.
The unique high surface area and tunable cavity size endow metal-organic cages (MOCs) with superior performance and broad application in gas adsorption and separation. Over the past three decades, ...for instance, numerous MOCs have been widely explored in adsorbing diverse types of gas including energy gases, greenhouse gases, toxic gases, noble gases,
etc.
To gain a better understanding of the structure-performance relationships, great endeavors have been devoted to ligand design, metal node regulation, active metal site construction, cavity size adjustment, and function-oriented ligand modification, thus opening up routes toward rationally designed MOCs with enhanced capabilities. Focusing on the unveiled structure-performance relationships of MOCs towards target gas molecules, this review consists of two parts, gas adsorption and gas separation, which are discussed separately. Each part discusses the cage assembly process, gas adsorption strategies, host-guest chemistry, and adsorption properties. Finally, we briefly overviewed the challenges and future directions in the rational development of MOC-based sorbents for application in challenging gas adsorption and separation, including the development of high adsorption capacity MOCs oriented by adsorbability and the development of highly selective adsorption MOCs oriented by separation performance.
In this highlight, we summarize the design principle and representative examples of MOCs for gas adsorption and separation, with the aim of providing a theoretical basis for designing more MOCs that can adsorb and purify gas.
"Anti-angiogenetic drugs plus chemotherapy" (anti-angio-chemo) and "immune checkpoint inhibitors plus chemotherapy" (ICI-chemo) are superior to traditional chemotherapy in the first-line treatment of ...patients with advanced non-small-cell lung cancer (NSCLC). However, in the absence of a direct comparison of ICI-chemo with anti-angio-chemo, the superior one between them has not been decided, and the benefit of adding anti-angiogenetic agents to ICI-chemo remains controversial. This study aimed to investigate the role of antiangiogenic agents for advanced NSCLC in the era of immunotherapy.
Eligible randomized controlled trials (RCTs) comparing chemotherapy versus therapeutic regimens involving ICIs or anti-angiogenetic drugs were included. Outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and rate of grade 3-4 toxicity assessment. R-4.3.1 was utilized to perform the analysis.
A total of 54 studies with a sample size of 25,046 were finally enrolled. "Atezolizumab + Bevacizumab + Chemotherapy" significantly improved the ORR compared with "Atezolizumab + Chemotherapy" (Odds ratio (OR) = 2.73, 95% confidence interval (CI): 1.27-5.87). The trend also favored "Atezolizumab + Bevacizumab + Chemotherapy" in PFS and OS (hazard ratio (HR) = 0.71, 95% CI: 0.39-1.31; HR = 0.94, 95% CI: 0.77-1.16, respectively). In addition, "Pembrolizumab + Chemotherapy" and "Camrelizumab + Chemotherapy" significantly prolonged the PFS compared to "Bevacizumab + Chemotherapy" (HR = 0.65, 95% CI: 0.46-0.92; HR = 0.63, 95% CI: 0.41-0.97; respectively). Meanwhile, "Pembrolizumab + Chemotherapy" and "Sintilimab + Chemotherapy" yielded more OS benefits than "Bevacizumab + Chemotherapy" (HR = 0.69, 95% CI: 0.56-0.83; HR = 0.64, 95%CI: 0.46-0.91; respectively). Scheme between "Atezolizumab + Bevacizumab + Chemotherapy" and "Atezolizumab + Chemotherapy" made no significant difference (OR = 1.18, 95%CI: 0.56-2.42) concerning the rate of grade 3-4 toxicity. It seemed that ICI-chemo yielded more improvement in quality-adjusted life-year (QALY) than "Bevacizumab + Chemotherapy" in cost-effectiveness analysis.
Our results suggest that ICI-chemo is associated with potentially longer survival, better cost-effectiveness outcomes, and comparable safety profiles than anti-angio-chemo. Also, adding bevacizumab to ICI-chemo seemed to provide additional therapeutic benefits without adding treatment burden. Our findings would supplement the current standard of care and help the design of future clinical trials for the first-line treatment of patients with advanced NSCLC.
Conventional horizontal twin-roll casting (TRC) with steel rollers generally possesses slow casting speed. In this study, the inclined TRC method with Cu rollers was proposed, which significantly ...increases the casting efficiency. A three-dimensional model of the inclined TRC was established, which revealed the temperature field, solid fraction, velocity distribution, and TRC microstructure of the AA6005 aluminum (Al) alloys by the finite element simulation. We considered the various effects of the pouring temperature, roll gap, and rolling speed on the outlet temperature of the inclined cast rolling zone, and determined the appropriate range of processing parameters. The casting speed of the inclined TRC process could reach ∼5.8–7.9 m/min when the roll gap was 2 and 3 mm. Due to the different contact areas between the melt and two rollers, the temperature field and the shape of the liquid hole were asymmetric, and the isotherm and solidification end point (Kiss point) shifted to the direction of the upper roller at the steady inclined TRC state. The columnar/equiaxed grain structure and the upper shift of central segregation in the inclined TRC sheets were successfully simulated by the finite element method, which was in good agreement with the experiments. Moreover, the inclined TRC method with Cu rollers has high cooling intensity and the potential to eliminate central segregation. The results of this study can effectively reduce the trial-and-error effort, and provide a new insight into the development of the TRC Al alloys.
Understanding the metal pollution can help governments and estuary management groups manage metal inputs. Here, we comprehensively analyzed the behaviors of seven metals Cd, Zn, Cu, As, Pb, Cr, and ...Hg in water and the responses of these metals to hydrological connectivity in the Pearl River Estuary. The analyses were based on the field measurements of August-2016 in the estuary and January-2016 in the upper river mouth. We also assessed the ecosystem health of these metals. Overall, this estuary had an overall moderate pollution level, with occasional severe perturbations. The mean concentration of individual metal was in the order of Zn > As > Cu > Cr > Pb > Cd > Hg. The eastern estuary was more heavily polluted by metals (notably, Zn, Cd, and Cu) than the western estuary; this condition was attributable to sewage and industrial effluent discharges from the eastern urban cities of Dongguan and Shenzhen. Longitudinally, high levels of Cd and Zn appeared in the upper estuary, while elevated levels of Cu, As, Pb, Cr, and Hg were found in the middle and lower estuaries. The riverine inputs and estuarine mixing significantly influenced the distribution and movement of trace metals in the estuary, and have contributed to phytoplankton productivity (chlorophyll-a > 10 μg/L). River inflow inhibited the vertical diffusion of metals, and tidal currents facilitated surface-to-bottom mixing. Cu and Cd posed ecological risks. We determined the source contributions and transport routes of the metals using principal component analysis combining with multiple linear regression. The results of this study suggest that the source apportionment of metals can help to manage the source input entering into the estuary. Further, identified hydrological connectivity of metals can inform water quality managers in the highly anthropogenically influenced estuary.
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•The metal concentration was in the order of Zn > As > Cu > Cr > Pb > Cd > Hg.•Ecological risks caused by Cu and Cd were high to the ecosystem’s health.•We discussed the effect of hydrological connectivity on metals.•River-tide dynamics influenced surface-to-bottom mixing of the metals.•PCA-MLR was useful to identify the source types and contributions of metals.
Bacteria from the genus
Geobacillus
are generally obligately thermophilic, with a unique bioenergy production capacity and unique enzymes.
Geobacillus
species were isolated primarily from hot ...springs, oilfields, and associated soils. They often exhibit unique survival patterns in these extreme oligotrophic environments. With the development of the microbial resources found in oilfields,
Geobacillus
spp. have been proven as valuable bacteria in many reports related to oilfields. After the isolation of
Geobacillus
by culture methods, more evidence was found that they possess the abilities of hydrocarbon utilization and bioemulsifier production. This paper mainly summarizes some characteristics of the
Geobacillus
species found in the oilfield environment, focusing on the inference and analysis of hydrocarbon degradation and bioemulsifier synthesis based on existing research, which may reveal their potential value in microbial enhanced oil recovery. It also provides references for understanding microbes in extreme environments.
Over the past few years, the field of regulated cell death continues to expand and novel mechanisms that orchestrate multiple regulated cell death pathways are being unveiled. Meanwhile, researchers ...are focused on targeting these regulated pathways which are closely associated with various diseases for diagnosis, treatment, and prognosis. However, the complexity of the mechanisms and the difficulties of distinguishing among various regulated types of cell death make it harder to carry out the work and delay its progression. Here, we provide a systematic guideline for the fundamental detection and distinction of the major regulated cell death pathways following morphological, biochemical, and functional perspectives. Moreover, a comprehensive evaluation of different assay methods is critically reviewed, helping researchers to make a reliable selection from among the cell death assays. Also, we highlight the recent events that have demonstrated some novel regulated cell death processes, including newly reported biomarkers (e.g., non-coding RNA, exosomes, and proteins) and detection techniques.
Osteoporotic bone defects result from an imbalance in bone homeostasis, excessive osteoclast activity, and the weakening of osteogenic mineralization, resulting in impaired bone regeneration. Herein, ...inspired by the hierarchical structures of mollusk nacre, nacre exhibits outstanding high-strength mechanical properties, which are in part due to its delicate layered structure. SrFe
12
O
19
nanoparticles and nano-layered double hydroxide (LDH) were incorporated into a bioactive chitosan (CS) matrix to form multifunctional layered nano-SrFe
12
O
19
-LDH/CS scaffolds. The compressive stress value of the internal ordered layer structure matches the trabecular bone (0.18 MPa). The as-released Mg
2+
ions from the nano-LDH can inhibit bone resorption in osteoclasts by inhibiting the NFκB signaling pathway. At the same time, the as-released Sr
2+
ions promote the high expression of osteoblast collagen 1 proteins and accelerate bone mineralization by activating the BMP-2/SMAD signaling pathway.
In vivo,
the Mg
2+
ions released from the SrFe
12
O
19
-LDH/CS scaffolds inhibited the release of pro-inflammatory factors (IL-1β and TNF-α), while the as-released Sr
2+
ions promoted osteoblastic proliferation and the mineralization of osteoblasts inside the layered SrFe
12
O
19
-LDH/CS scaffolds. Immunofluorescence for OPG, RANKL, and CD31, showed that stable vasculature could be formed inside the layered SrFe
12
O
19
-LDH/CS scaffolds. Hence, this study on multifunctional SrFe
12
O
19
-LDH/CS scaffolds clarifies the regulatory mechanism of osteoporotic bone regeneration and is expected to provide a theoretical basis for the research, development, and clinical application of this scaffold on osteoporotic bone defects.
Image 1
•
1, SrFe
12
O
19
nanoparticles and LDH were incorporated into a bioactive CS matrix.
•
2, SrFe
12
O
19
-LDH/CS scaffolds were prepared as a layered scaffold to increase mechanical strength.
•
3, The slow release of Mg
2+
and Sr
2+
could maintain bone homeostasis.
•
4, The scaffolds also promote the formation of new blood vessels.
The lack of clamping force detection function of the surgical robot's end effector poses a challenge to the operation of doctors, which requires sensing and rapid response to transient forces during ...surgery. Therefore, it is necessary to design a surgical robot with a clamping force detection function. In this paper, the piezoelectric sensor was prepared with tetrapod-like zinc oxide (T-ZnO) as the primary raw material. The performance of the sensors was enhanced by adjusting the preparation parameters, and the prepared sensors were characterized by high sensitivity (182.5 mV/N). This work is the first to apply the piezoelectric sensor made of T-ZnO to the end fixtures of surgical robots, and the results show that the sensor's output voltage in the end fixture of the surgical robot increases with the increase of pressure, and the sensor has different responses to the clamped object with different stiffness. The sensor can be applied to the end fixture of surgical robots.
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•The first to apply sensor made of T-ZnO to the end fixture of the surgical robot.•The prepared sensors exhibit high sensitivity of 182.5 mV/N.•We have identified the factors that affect the performance of the sensor.•The sensor can be applied in the end fixture of the surgical robot.
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