High internal phase emulsions gel ink for direct-ink-writing 3D printing of liquid metal.

3D printing of liquid metal remains a big challenge due to its low viscosity and large surface tension. In this study, we use Carbopol hydrogel and liquid gallium-indium alloy to prepare a liquid metal high internal phase emulsion gel ink, which can be used for direct-ink-writing 3D printing. The high volume fraction (up to 82.5%) of the liquid metal dispersed phase gives the ink excellent elastic properties, while the Carbopol hydrogel, as the continuous phase, provides lubrication for the liquid metal droplets, ensuring smooth flow of the ink during shear extrusion. These enable high-resolution and shape-stable 3D printing of three-dimensional structures. Moreover, the liquid metal droplets exhibit an electrocapillary phenomenon in the Carbopol hydrogel, which allows for demulsification by an electric field and enables electrical connectivity between droplets. We have also achieved the printing of ink on flexible, non-planar structures, and demonstrated the potential for alternating printing with various materials.

Oligo-residual disease in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer: incidence, pattern of failure, and clinical value of local consolidative therapy.

OBJECTIVES: To investigate the feasibility and potential clinical value of local consolidative therapy (LCT) in PD-1/PD-L1 inhibitor-treated metastatic non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients with measurable disease in three academic centers were screened and those with adequate follow-up were included. Oligo-residual disease (ORD) was defined as residual tumors limited to three organs and five lesions evaluated at the best response among patients with partial response or stable disease after PD-1/PD-L1 inhibitors. Oligometastatic and multiple-metastatic disease (OMD/MMD) were similarly classified at baseline. Locoregional interventions, administered after effective treatment of PD-1/PD-L1 inhibitors and before initial disease progression, were defined as LCT. Patterns of initial progressive disease (PD) were classified as involving only residual sites (RP), only new sites (NP), or a combination of both (BP). RESULTS: Among the 698 patients included, ORD was documented in 73 (47.1%) of 155 patients with baseline OMD and 60 (11.0%) of 543 patients with baseline MMD. With a median follow-up of 31.0 (range, 6.0-53.0) months, 108 patients with ORD developed initial PD, with RP, NP, and BP occurring in 51 (47%), 23 (21.3%), and 34 (31.5%), respectively. Among the 133 patients with ORD, those receiving LCT (n = 43) had longer progression-free survival (HR = 0.58, 95% CI 0.40-0.85, p = 0.01) and overall survival (HR = 0.49, 95% CI 0.30-0.79, p < 0.0001). CONCLUSION: ORD occurs with a clinically relevant frequency among PD-1/PD-L1 inhibitor-treated metastatic NSCLC patients and LCT may provide extra survival benefits in those with ORD.

Enhancing the prediction of symptomatic radiation pneumonitis for locally advanced non-small-cell lung cancer by combining 3D deep learning-derived imaging features with dose-volume metrics: a two-center study.

OBJECTIVE: This study aims to examine the ability of deep learning (DL)-derived imaging features for the prediction of radiation pneumonitis (RP) in locally advanced non-small-cell lung cancer (LA-NSCLC) patients. MATERIALS AND METHODS: The study cohort consisted of 90 patients from the Fudan University Shanghai Cancer Center and 59 patients from the Affiliated Hospital of Jiangnan University. Occurrences of RP were used as the endpoint event. A total of 512 3D DL-derived features were extracted from two regions of interest (lung-PTV and PTV-GTV) delineated on the pre-radiotherapy planning CT. Feature selection was done using LASSO regression, and the classification models were built using the multilayered perceptron method. Performances of the developed models were evaluated by receiver operating characteristic curve analysis. In addition, the developed models were supplemented with clinical variables and dose-volume metrics of relevance to search for increased predictive value. RESULTS: The predictive model using DL features derived from lung-PTV outperformed the one based on features extracted from PTV-GTV, with AUCs of 0.921 and 0.892, respectively, in the internal test dataset. Furthermore, incorporating the dose-volume metric V30Gy into the predictive model using features from lung-PTV resulted in an improvement of AUCs from 0.835 to 0.881 for the training data and from 0.690 to 0.746 for the validation data, respectively (DeLong p < 0.05). CONCLUSION: Imaging features extracted from pre-radiotherapy planning CT using 3D DL networks could predict radiation pneumonitis and may be of clinical value for risk stratification and toxicity management in LA-NSCLC patients. CLINICAL RELEVANCE STATEMENT: Integrating DL-derived features with dose-volume metrics provides a promising noninvasive method to predict radiation pneumonitis in LA-NSCLC lung cancer radiotherapy, thus improving individualized treatment and patient outcomes.

Self-Compositing: A Efficient Method of Improving the Electrical Conductivity of Graphene Nanoplatelet/Thermosetting Resin Composites.

Conductive composites based on thermosetting resins have broad applications in various fields. In this paper, a new self-compositing strategy is developed for improving the conductivity of graphene nanoplatelet/thermosetting resin composites by optimizing the transport channels. To implement this strategy, conventional graphene nanoplatelet/thermosetting resin is crushed into micron-sized composite powders, which are mixed with graphene nanoplatelets to form novel complex fillers to prepare the self-composited materials with thermosetting resins. A highly conductive compact graphene layer is formed on the surface of the crushed composite powders, while the addition of the micron-sized powder induces the orientation of graphene nanoplatelets in the resin matrix. Therefore, a highly conductive network is constructed inside the self-composited material, significantly enhancing the electrical conductivity. The composite materials based on epoxy resin, cyanate resin, and unsaturated polyester are prepared with this method, reflecting that the method is universal for preparing composites based on thermosetting resins. The highest electrical conductivity of the self-composited material based on unsaturated polyester is as high as 25.9 S m-1 . This self-compositing strategy is simple, efficient, and compatible with large-scale industrial production, thus it is a promising and general way to enhance the conductivity of thermosetting resin matrix composites.

Stomatal responses of terrestrial plants to global change.

Quantifying the stomatal responses of plants to global change factors is crucial for modeling terrestrial carbon and water cycles. Here we synthesize worldwide experimental data to show that stomatal conductance (gs) decreases with elevated carbon dioxide (CO2), warming, decreased precipitation, and tropospheric ozone pollution, but increases with increased precipitation and nitrogen (N) deposition. These responses vary with treatment magnitude, plant attributes (ambient gs, vegetation biomes, and plant functional types), and climate. All two-factor combinations (except warming + N deposition) significantly reduce gs, and their individual effects are commonly additive but tend to be antagonistic as the effect sizes increased. We further show that rising CO2 and warming would dominate the future change of plant gs across biomes. The results of our meta-analysis provide a foundation for understanding and predicting plant gs across biomes and guiding manipulative experiment designs in a real world where global change factors do not occur in isolation.

High-strength and machinable load-bearing integrated electrochemical capacitors based on polymeric solid electrolyte.

Load bearing/energy storage integrated devices (LEIDs) allow using structural parts to store energy, and thus become a promising solution to boost the overall energy density of mobile energy storage systems, such as electric cars and drones. Herein, with a new high-strength solid electrolyte, we prepare a practical high-performance load-bearing/energy storage integrated electrochemical capacitors with excellent mechanical strength (flexural modulus: 18.1 GPa, flexural strength: 160.0 MPa) and high energy storage ability (specific capacitance: 32.4 mF cm-2, energy density: 0.13 Wh m-2, maximum power density: 1.3 W m-2). We design and compare two basic types of multilayered structures for LEID, which significantly enhance the practical bearing ability and working flexibility of the device. Besides, we also demonstrate the excellent processability of the LEID, by forming them into curved shapes, and secondarily machining and assembling them into complex structures without affecting their energy storage ability.

Pattern of failure and clinical value of local therapy for oligo-recurrence in locally advanced non-small cell lung cancer after definitive chemoradiation: Impact of driver mutation status.

INTRODUCTION: Considerable differences of treatment response and pattern of failure may exist between definitive chemoradiation (CRT) treated locally advanced non-small cell lung cancer (LA-NSCLC) patients. The clinical value of additional tyrosine kinase inhibitors (TKIs) before disease recurrence and salvage local therapy after initial recurrent disease remain controversial. METHODS AND MATERIALS: Consecutive LA-NSCLC patients receiving definitive CRT and having definite results about driver mutations (EGFR, ALK and ROS1) were retrospectively reviewed. Initial recurrent disease was classified as in-field recurrence, out-of-field recurrence and distant metastasis. Recurrent disease occurred only in the brain or limited to ≤3 extra-cranial organs and ≤5 extra-cranial lesions, was defined as oligo-recurrence. Progression free survival and overall survival (OS) were calculated from diagnosis to disease progression or death, and to death, respectively. OS2 was measured from initial disease recurrence to death among patients who had recurrent disease. RESULTS: Of the 153 enrolled patients, 39 had driver mutations and 13 received additional TKI therapy besides definitive CRT. Patients harboring driver mutations but without additional TKI therapy had a similar PFS and significantly longer OS (p = 0.032) than those without driver mutations. Additional TKI therapy prolonged PFS (p = 0.021) but not OS among patients with driver mutations. No significant difference of pattern of failure was observed between patient subgroups stratified by the status of driver mutations and the usage of additional TKI therapy. Furthermore, 57 of the 95 patients with initial recurrent disease developed oligo-recurrence and salvage local therapy significantly improved OS2 (p = 0.01) among patients with oligo-recurrence disease. CONCLUSION: LA-NSCLC patients receiving definitive CRT generally had similar PFS and pattern of treatment failure, regardless of driver mutation status. Additional TKI therapy besides definitive CRT could prolong PFS but not OS. The majority of recurrent disease after definitive CRT belongs to oligo-recurrence and salvage local therapy may provide survival benefit.

Accurate in situ measurements of thermoelectric transport properties at high pressure and high temperature.

Regulating electron structure and electron-phonon coupling by means of pressure and temperature is an effective way to optimize thermoelectric properties. However, in situ testing of thermoelectric transport performance under pressure and temperature is hindered by technical constraints that obscure the intrinsic effects of pressure and temperature on thermoelectric properties. In the present study, a new reliable assembly was developed for testing the in situ thermoelectric transport performance of materials at high pressure and high temperature (HPHT). This reduces the influence of thermal effects on the test results and improves the success rate of in situ experiments at HPHT. The Seebeck coefficient and electrical resistivity of α-Cu2Se were measured under HPHT, and the former was found to increase with increasing pressure and temperature; for the latter, although an increase in the pressure acted to lower the electrical resistivity, an increase in the temperature acted to increase it. On increasing pressure from 0.8 to 3 GPa at 333 K, the optimal power factor of α-Cu2Se was increased by ∼76% from 2.36 × 10-4-4.15 × 10-4 W m-1 K-2, and the higher pressure meant that α-Cu2Se had its maximum power factor at lower temperature. The present work is particularly important for understanding the thermoelectric mechanism under HPHT.

Freezing-triggered gelation of quaternized chitosan reinforced with microfibrillated cellulose for highly efficient removal of bilirubin.

The highly efficient removal of bilirubin from blood by hemoperfusion for liver failure therapy remains a challenge in the clinical field due to the low adsorption capacity and poor hemocompatibility of currently used carbon-based adsorbents. Polysaccharide-based cryogels seem to be promising candidates for hemoperfusion adsorbents owing to their inherited excellent hemocompatibility. However, the weak mechanical strength and relatively low adsorption capacity of polysaccharide-based cryogels limited their application in bilirubin adsorption. In this work, we presented a freezing-triggered strategy to fabricate QCS/MFC cryogels, which were formed by quaternized chitosan (QCS) crosslinked with divinylsulfonyl methane (BVSM) and reinforced with microfibrillated cellulose (MFC). Ice crystal exclusions triggered the chemical crosslinking to generate the cryogels with dense pore walls. The obtained QCS/MFC cryogels were characterized by FTIR, SEM, stress-strain test, and hemocompatibility assay, which exhibited interconnected macroporous structures, excellent shape-recovery and mechanical performance, and outstanding blood compatibility. Due to the quaternary ammonium functionalization of chitosan, the QCS/MFC showed a high adsorption capacity of 250 mg g-1 and a short adsorption equilibrium time of 3 h. More importantly, the QCS/MFC still exhibited high adsorption efficiency (over 49.7%) in the presence of 40 g L-1 albumin. Furthermore, the QCS/MFC could also maintain high dynamic adsorption efficiency in self-made hemoperfusion devices. This facile approach provides a new avenue to develop high-performance hemoperfusion adsorbents for bilirubin removal, showing great promise for the translational therapy of hyperbilirubinemia.

Clinical value of PET/CT in identifying patients with oligometastatic/oligoprogressive disease among first-line tyrosine kinase inhibitor-treated advanced EGFR-mutant non-small cell lung cancer: Implications from survival comparisons.

OBJECTIVE: Local therapy (LT) could potentially prolong the survival of patient with advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) receiving tyrosine kinase inhibitors (TKIs) and harboring oligometastatic/oligoprogressive disease (OMD/OPD). However, the optimal imaging method for identifying patients with OMD/OPD remains controversial. The objective of this study was to investigate the clinical value of incorporating PET/CT in detecting patients with OMD/OPD. METHODS: Consecutive cases with metastatic EGFR-mutant NSCLC undergoing first-line EGFR-TKI treatment were retrospectively screened and those receiving baseline PET/CT and brain magnetic resonance imaging (MRI) or complete conventional imaging (CIM), including brain MRI, chest computed tomography (CT), abdomen ultrasound or CT and bone scintigraphy were included. OMD/OPD was defined as metastases/progressions documented at a maximum of five lesions and three organs, otherwise was defined as multiple metastatic/progressive disease (MMD/MPD). Progression-free survival (PFS) and overall survival (OS) were analyzed. RESULTS: Of the 392 patients evaluated, baseline OMD was detected in 22.7% (53/233) of patients by PET/CT and in 18.2% (29/159) of patients by CIM (p = 0.171). Among the patients evaluated with baseline PET/CT, patients with OMD had longer PFS (p = 0.016) and tendency of improved OS (p = 0.058) than those with MMD. However, this result was not observed with patients evaluated using baseline CIM. With a median follow-up of 24.2 (range, 1.1-124.6) months, 297 patients had their first disease progression (FPD), of whom 164 (55.2%) had adequate imaging scans to analyze the tumor distributions at FPD comprehensively. OPD was detected in 63.0% (34/54) and 35.0% (39/110) of patients among the PET/CT and CIM assessed group (p = 0.003), respectively. Among the PET/CT assessed group, patients with OPD had significantly longer post-progressive overall survival (OS2) than those with MPD (p = 0.011). However, no significant difference of OS2 in the CIM assessed group was found. CONCLUSION: Patients with OMD/OPD, evaluated by PET/CT but not CIM, generally had more favorable survival outcomes than those with MMD/MPD among patients with metastatic NSCLC undergoing first-line EGFR-TKI treatment. ADVANCES IN KNOWLEDGE: PET/CT seems to affect the survival of patients under first-line EGFR-TKI treated metastatic NSCLC with OMD/OPD.

Brain metastases, patterns of intracranial progression, and the clinical value of upfront cranial radiotherapy in patients with metastatic non-small cell lung cancer treated with PD-1/PD-L1 inhibitors.

Background: Despite the emergence of programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs), knowledge gaps remain regarding the impact and timing of cranial radiotherapy for patients receiving anti-PD-1/PD-L1 therapy. Methods: Data were collected from 461 consecutive patients who received anti-PD-1/PD-L1 therapy for metastatic NSCLC at three institutions between June 2017 and September 2020. Intracranial progressive disease (PD) at the original disease sites, new sites, or both sites were classified as original-site PD (OPD), new-site PD (NPD), and original-and-new-site PD (ONPD), respectively. Patients with baseline BMs were categorized based on whether they received upfront cranial radiotherapy (uCRT) at any time point between the introduction of anti-PD-1/PD-L1 therapy and the first subsequent progression. Results: Of the 461 patients enrolled, 110 (23.9%) had BMs at baseline. The presence of BMs did not show independent prognostic value for progression-free survival (PFS) or overall survival (OS). During a median follow-up of 13.2 months, 96 patients with BMs developed PD, of whom 53 (55.2%) experienced intracranial PD. OPD, NPD, and ONPD were observed in 50.9%, 18.9%, and 30.2% of patients, respectively. Patients who received uCRT exhibited a longer median OS than those with BMs who did not receive uCRT (25.4 vs. 14.6 months, HR: 0.52, 95% CI: 0.29-0.91, P=0.041); this survival advantage was more prominent in patients with 1-4 BMs (median OS, 25.4 vs. 17.0 months, HR: 0.42, 95% CI: 0.22-0.81, P=0.024), and uCRT was independently associated with OS among these patients. Conclusions: The presence of BMs at baseline was not associated with poorer OS in patients with metastatic NSCLC treated with anti-PD-1/PD-L1 therapy. Intracranial progression on PD-l/PD-L1 inhibitors predominately occurred at the original BM sites. The use of uCRT may improve OS, especially in NSCLC patients with 1-4 BMs.

Atypical Response in Metastatic Non-Small Cell Lung Cancer Treated with PD-1/PD-L1 Inhibitors: Radiographic Patterns and Clinical Value of Local Therapy.

PURPOSE: To explore the clinical characteristics, management, and survival outcomes of advanced NSCLC patients treated with PD-1/PD-L1 inhibitors who presented with an atypical response (AR). METHODS: A total of 926 PD-1/PD-L1-inhibitor-treated patients with metastatic NSCLC from three academic centers were retrospectively reviewed. All measurable lesions were evaluated by RECIST version 1.1. RESULTS: Fifty-six (6.1%) patients developed AR. The median time to the occurrence of AR was 2.0 months. Patients with no fewer than 3 metastatic organs at baseline were more prone to develop AR in advanced NSCLC (p = 0.038). The common sites of progressive lesions were lymph nodes (33.8%) and lungs (29.7%). The majority (78.2%) of patients with AR had only 1-2 progressive tumor lesions, and most (89.1%) of the progressive lesions developed from originally existing tumor sites. There was no significance in terms of survival between patients with AR and those with typical response (TR). Local therapy was an independent predictor for PFS of patients with AR (p = 0.025). CONCLUSIONS: AR was not an uncommon event in patients with metastatic NSCLC treated with PD-1/PD-L1 inhibitors, and it had a comparable prognosis to those with TR. Proper local therapy targeting progressive lesions without discontinuing original PD-1/PD-L1 inhibitors may improve patient survival.

Novel and wet-resilient cellulose nanofiber cryogels with tunable porosity and improved mechanical strength for methyl orange dyes removal.

Interconnected macro-porous cryogels with robust and pore-tunable structures have been fabricated using chemically crosslinked microfibrillated cellulose (MFC). Periodate oxidation was initially conducted to introduce aldehyde groups into the MFC surface, followed by the freeze-induced chemical crosslinking via the formation of hemiacetal bonds between aldehyde and hydroxyl at -12 °C. The cryogels with pore-tunable structures and sharply enhanced mechanical strengths were finally achieved by re-assembly of MFCs through soaking in NaIO4 solution. Furthermore, the MFC cryogels were post-crosslinked by polyethyleneimine (PEI), bestowing the cryogels with the capability of adsorbing anionic dyes. The stress of the PEI-MFC cryogel at the 80% strain was determined to be 304.5 kPa, which is the maximum value for the nanocellulose-based cryogels reported so far. Finally, the adsorption performances of PEI-MFC cryogels for methyl orange (MO) were evaluated. Maximum adsorption capacity of 500 mg/g could be obtained by the Langmuir model, outperforming that of previous absorbent materials. Reuse experiments indicated that over 90% of adsorption capacity was retained after 6 cycles. Continuous clean-up experiments demonstrated excellent MO removal abilities of the PEI-MFC cryogel. This study shows that the novel, green strategy to fabricate the robust cryogel extends the practical applications of nanocellulose adsorbents for environmental remediation.

Revealing the Unusual Boron-Pinned Layered Substructure in Superconducting Hard Molybdenum Semiboride.

Improving the poor electrical conductivity of hard materials is important, as it will benefit their application. High-hardness metallic Mo2B was synthesized by high-pressure and high-temperature methods. Temperature-dependent resistivity measurements suggested that Mo2B has excellent metallic conductivity properties and is a weakly coupled superconductor with a T c of 6.0 K. The Vickers hardness of the metal-rich molybdenum semiboride reaches 16.5 GPa, exceeding the hardness of MoB and MoB2. The results showed that a proper boron concentration can improve the mechanical properties, not necessarily a high boron concentration. First-principles calculations revealed that the pinning effect of light elements is related to hardness. The high hardness of boron-pinned layered Mo2B demonstrated that the design of high-hardness conductive materials should be based on the structure formed by light elements rather than high-concentration light elements.

Mechanisms and Implications of CDK4/6 Inhibitors for the Treatment of NSCLC.

Cyclin-dependent kinases (CDKs) are key regulators of cell cycle progression in malignant tumor cells and play an important role through complex molecular interactions. Dysregulation of CDK dependent pathways is often found in non-small cell lung cancer, which indicates its vulnerability and can be used in clinical benefit. CDK4/6 inhibitors can prevent tumor cells from entering the G approved 1 and S phases, which have been studied in a series of explorations and brought great clinical effect to patients and encouragement to both physicians and researchers, thereby showing potential as a new therapeutic agent. A series of preclinical and clinical studies have been carried out on CDK4/6 inhibitors in NSCLC, and have been achieved some results, which may become a new potential treatment in the future. This review focuses on the research progress on CDK4/6 inhibitors in NSCLC, particularly the mechanisms of action, drugs, clinical research progress, and future application.

Shapeable and underwater super-elastic cellulose nanofiber/alginate cryogels by freezing-induced oxa-Michael reaction for efficient protein purification.

Construction of monolithic cryogels that can efficiently adsorb proteins is of great significance in biotechnological and pharmaceutical industries. Herein, a novel approach is presented to fabricate microfibrillated cellulose (MFC)/sodium alginate (SA) cryogels by using freezing-induced oxa-Michael reaction at -12 °C. Thanks to the controllable reactiveness of divinyl sulfone (DVS), cryo-concentrated pH increase activates the oxa-Michael reaction between DVS and hydroxyl groups of MFCs and SAs. The obtained composite cryogel exhibits outstanding underwater shape recovery and excellent fatigue resistance. Moreover, the MFC/SAs reveal a high lysozyme adsorption capacity of 294.12 mg/g, surpassing most of absorbent materials previously reported. Furthermore, the cryogel-packed column can purify lysozyme continuously from chicken egg white, highlighting its outstanding practical application performance. Reuse experiments indicated that over 90% of lysozyme extraction capacity was retained after 6 cycles. This work provides a new avenue to design and develop next-generation chromatographic media of natural polysaccharide-based cryogel for protein purification.

ZnO nanorods/Fe3O4-graphene oxide/metal-organic framework nanocomposite: recyclable and robust photocatalyst for degradation of pharmaceutical pollutants.

Nanosized semiconductors are widely utilized as solar energy based photocatalyst. However, the deficiencies such as poor adsorption toward contaminants and recyclability issues, rapid recombination of photo-introduced radicals, and deactivation by scavengers are still be the obstacle. To addressing those obstacles, zeolitic imidazolate framework-8 (ZIF-8), photosensitive ZnO, and paramagnetic Fe3O4 were anchored on conductive graphene oxide (GO) to prepare a nanocomposite photocatalyst ZnO/Fe3O4-GO/ZIF. The photocatalyst showed good robustness to scavengers of hydroxyl radicals (OH•), superoxide radicals (O2•-), and hole (h+) with hydrophobic ZIF-8 modified surface. Finally, four pharmaceuticals (sulfamethazine, metronidazole, norfloxacin, and 4-acetaminophen) were degraded rapidly under simulated solar irradiation for 1 h, and the photocatalyst could be recycled at least ten times without obvious deactivation. The final results show that combination of semiconductor, graphene oxide and ZIF-8 is a good idea for construction of efficient photocatalyst. It offers new views in interface modification of nanomaterials, photocatalysis, and adsorption.

The effects of elevated CO2, elevated O3, elevated temperature, and drought on plant leaf gas exchanges: a global meta-analysis of experimental studies.

Global change significantly influences plant leaf gas exchange, which affects the carbon-water cycle of terrestrial ecosystems. However, the magnitudes of the effects of multiple global change factors on leaf gas exchanges are currently lacking. Therefore, a global meta-analysis of 337 published articles was conducted to determine the effects of elevated CO2 (eCO2), elevated O3 (eO3), elevated temperature (eT), and drought on plant leaf gas exchanges. The results indicated that (1) the overall responses of photosynthesis rate (Pn) and instantaneous water use efficiency (WUEi) to eCO2 increased by 28.6% and 58.6%. But transpiration rate (Tr) and stomatal conductance (gs) responded negatively to eCO2 (- 17.5% and - 17.2%, respectively). Furthermore, all Pn, gs, and WUEi responded negatively to eO3 (- 32.7%, - 24.6%, and - 27.1%), eT (- 23.2%, - 10.8%, and - 28.9%), and drought (- 53.6%, - 59.3%, and - 4.6%, respectively), regardless of functional groups and various complex experimental conditions. (2) Elevated CO2 increased WUEi combined with eO3, eT, and drought (26.6%, 36.0%, and 58.6%, respectively, for eCO2 + eO3, eCO2 + eT, and eCO2 + drought) and mitigated their negative impacts on Pn to some extent. (3) Plant form and foliage type play an important role in the responses of leaf gas exchanges. Trees responded mostly to eCO2, but responded least to eT in Pn, Tr, gs, and WUEi compared with shrubs and herbs. Evergreen broad-leaved species were more responsive to eCO2 and drought. (4) The stress level of each factor can also significantly influence the responses of leaf gas exchanges to environment change. Hopefully, the quantitative results are helpful for the further assessments of the terrestrial carbon-water cycle.

Protective effect of trimetazidine in radiation-induced cardiac fibrosis in mice.

Radiation-induced heart damage is a serious side effect caused by radiotherapy, especially during the treatment of cancer near the chest. Trimetazidine is effective at reducing inflammation in the heart, but how it affects radiation-induced cardiac fibrosis (RICF) is unknown. To investigate the potential effect and molecular mechanism, we designed this project with a C57BL6 male mouse model supposing trimetazidine could inhibit RICF in mice. During the experiment, mice were randomly divided into six groups including a control group (Con), radiation-damaged model group (Mod) and four experimental groups receiving low-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimetazidine before or after radiation treatment. Apart from the control group, all mice chests were exposed to 6 MV X-rays at a single dose of 20 Gy to induce RICF, and tissue analysis was done at 8 weeks after irradiation. Fibroblast or interstitial tissues and cardiac fibrosis-like characteristics were determined using haematoxylin and eosin and Masson staining, which can be used to assess myocardial fibrosis. Immunohistochemical analysis and RT-PCR were used to determine gene expression and study the molecular mechanism. As a result, this study suggests that trimetazidine inhibits RICF by reducing gene expression related to myocyte apoptosis and fibrosis formation, i.e. connective tissue growth factor (CTGF), transforming growth factor (TGF)-ß1, smad2 and smad3. In conclusion, by regulating the CTGF/TGF-ß1/Smad pathway, trimetazidine could be a prospective drug for clinical treatment of RICF.