Northward shift of Indian summer monsoon and intensifying winter westerlies cause stronger precipitation seasonality over Pamirs and its downstream basins in the 21st century.

Hydroclimate will change over Pamirs and its downstream basins (PDB), including Indus River, Tarim River, Amu Darya and Syr Darya Basins, in response to the variation of Indian summer monsoon (ISM) and mid-latitude westerlies. However, the precipitation variation and its mechanism over PDB in the 21st century are yet not fully understood. Here, the best models ensemble selected from 25 CMIP6 models under SSP2-4.5 and SSP5-8.5 scenarios is applied to detect the precipitation variations over PDB in the 21st century. A remarkable dipolar pattern is found in both summer and winter precipitation over PDB, particularly in the central Indus River Basin and upper Amu and Syr Darya Basins. The central Indus River Basin (upper Amu and Syr Darya Basins) will experience an increasingly wet (dry) summer in response to northward ISM and a dry (wet) winter driven by mid-latitude westerlies. The amplifying dipolar pattern of seasonal precipitation thus increases the water resource vulnerability over PDB and emphasizes the role of Pamirs in modulating the water resources over surrounding basins, especially the Amu Darya and Syr Darya Basins in the future. The findings underscore the need for prioritizing policies by considering the impacts of precipitation seasonality on social planning.

NK-92MI Cells Engineered with Anti-claudin-6 Chimeric Antigen Receptors in Immunotherapy for Ovarian Cancer.

Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to be explored. Methods: CLDN6 expression in primary human ovarian cancer, normal tissues and cell lines were detected by immunohistochemistry and western blot. Two types of third-generation CAR NK-92MI cells targeting CLDN6, CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) and CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB) were constructed by lentivirus transfection, sorted by flow cytometry and verified by western blot and qPCR. OVCAR-3, SK-OV-3, A2780, Hey and PC-3 cells expressing the GFP and luciferase genes were transduced. Subcutaneous and intraperitoneal tumor models were established via NSG mice. The ability of CLDN6-CAR NK cells to kill CLDN6-positive ovarian cancer cells were evaluated in vitro and in vivo by live cell imaging and bioluminescence imaging. Results: Both CLDN6-CAR1 and CLDN6-CAR2 NK-92MI cells could specifically killed CLDN6-positive ovarian cancer cells (OVCAR-3, SK-OV-3, A2780 and Hey), rather than CLDN6 negative cell (PC-3), in vitro. CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) exhibited stronger cytotoxicity than CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB). Furthermore, CLDN6-CAR1 NK cells could effectively eliminate ovarian cancer cells in subcutaneous and intraperitoneal tumor models. More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. Conclusions: These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.

Research on rice disease recognition based on improved SPPFCSPC-G YOLOv5 network.

Spatial Pyramid Pooling (SPP) is important in capturing remote contextual information for pixel-level prediction tasks in scene-resolved detection of rice diseases. In this paper, the detection objects of the rice disease dataset used in this paper have almost the same target size and do not need to be passed through different filters to obtain different receptive fields of view. Therefore, this paper proposed a new pooling structure, SPPFCSPC-G, which split the feature vector into 2 channels for processing. One channel was processed using grouped 1×1 Conv, while the other channel mainly used multiple filters with the same parallel structure (5×5 MaxPool). Additionally, multiple 1×1 and 3×3 grouped convolutions were concatenated in series in that branch (Group-Conv) to extract more complex features in rice. Finally, the 2 parts were connected (Concat) together, with each convolutional layer Conv divided into 4 groups as a way to reduce the amount of computation in the model. The project team incorporated SPPFCSPC-G into the Backbone of YOLOv5 and trained it on NVIDIA Tesla T4 (GPU). The experimental results showed that the performance of the method used in this paper improved, including Precision, Recall, mAP, and training speed, while reducing the size of computational parameters (Parameters), computational volume (GFLOPs), and model size (Param.). The project team carried out the trained YOLOv5 model on Intel Core i5 (CPU) for inference detection of rice leaves in real scenarios, and the experiments showed that both pre-inference and actual inference were faster. Moreover, the consumption of computational resources was almost minimized, and the model effectively identified rice diseases.

Impact of genetic patterns on sorafenib efficacy in patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation: a multi-center, cohort study.

Sorafenib therapy improves overall survival (OS) in patients with FLT3 internal tandem duplication (ITD) acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation. We explored the efficacy of sorafenib therapy in this population with different concomitant genetic patterns. In this multi-center, cohort study, we enrolled patients with FLT3-ITD AML undergoing allogenic hematopoietic cell transplantation. Patients with sorafenib maintenance post-transplantation for at least four weeks were allocated to the sorafenib group, and otherwise to the control group. Endpoints were OS, disease-free survival, and relapse for the whole cohort and OS for genetic pattern subgroups. Among 613 patients enrolled, 275 were in the sorafenib and 338 the control group. Median follow-up was 36.5 (interquartile range (IQR), 25.2-44.7) months post-transplantation. The 3-year OS post-transplantation was 79.6% (95% confidential interval (CI) 74.8%-84.6%) and 65.2% (95% CI 60.3%-70.6%) (Hazard ratio (HR) 0.50, 95% CI 0.37-0.69; P < 0.0001) in both groups. Sorafenib maintenance post-transplantation improved OS in the favorable (HR 0.33, 95% CI 0.14-0.77; P = 0.011) and adverse (HR 0.56, 95% CI 0.33-0.93; P = 0.026) ELN 2017 risk subgroups. Patients with mutated NPM1, DNMT3A, co-occurring NPM1/DNMT3A, "activated signaling" and "DNA methylation" genes benefited in OS from sorafenib maintenance, while those carrying CEBPA, "tumor suppressors" and "myeloid transcription factors" genes did not. Patients with FLT3-ITDhigh and FLT3-ITDlow AML both benefited in OS from sorafenib maintenance. Our results identify the response of genetic patterns to sorafenib maintenance, providing new viewpoints for the optimal use of sorafenib in FLT3-ITD AML in the transplantation setting.

Fine-tuning benzazole-based probe for the ultrasensitive detection of Hg2+ in water samples and seaweed samples.

Developing potentially toxic metal ion probes is significant for environment and food safety. Although Hg2+ probes have been extensively studied, small molecule fluorophores that can integrate two applications of visual detection and separation into one unit remain challenging to access. Herein, by incorporating triphenylamine (TPA) into tridentate skeleton with an acetylene bridge, 2,6-bisbenzimidazolpyridine-TPA (4a), 2,6-bisbenzothiazolylpyridine-TPA (4b) and 2,6-bisbenzothiazolylpyridine-TPA (4c) were first constructed, expectably showing distinct solvatochromism and dual-state emission properties. Since the diverse emission properties, the fluorescence detection of 4a-4b can be achieved with an ultrasensitive response (LOD = 10-11 M) and efficient removal of Hg2+. More interestingly, 4a-4b can not only be developed into paper/film sensing platform, but also reliably detect Hg2+ in real water and seaweed samples, with recoveries ranging from 97.3% to 107.8% and a relative standard deviation of less than 5%, indicating that they have excellent application potential in the field of environmental and food chemistry.

Long-Term Soil Drought Limits Starch Accumulation by Altering Sucrose Transport and Starch Synthesis in Sweet Potato Tuberous Root.

In this study, the influences of long-term soil drought with three levels [soil-relative water content (SRWC) (75 ± 5)%, as the control; SRWC (55 ± 5)%, mild drought; SRWC (45 ± 5)%, severe drought] were investigated on sucrose-starch metabolism in sweet potato tuberous roots (TRs) by pot experiment. Compared to the control, drought stress increased soluble sugar and sucrose content by 4-60% and 9-75%, respectively, but reduced starch accumulation by 30-66% through decreasing the starch accumulate rate in TRs. In the drought-treated TRs, the inhibition of sucrose decomposition was attributed to the reduced activities of acid invertase (AI) and alkaline invertase (AKI) and the IbA-INV3 expression, rather than sucrose synthase (SuSy), consequently leading to the increased sucrose content in TRs. In addition, starch synthesis was inhibited mainly by reducing ADP-glucose pyrophosphorylase (AGPase), granular starch synthase (GBSS) and starch branching enzyme (SBE) activities in TRs under drought stress, and AGPase was the rate-limiting enzyme. Furthermore, soil drought remarkably up-regulated the IbSWEET11, IbSWEET605, and IbSUT4 expressions in Jishu 26 TRs, while it down-regulated or had no significant differences in Xushu 32 and Ningzishu 1 TRs. These results suggested that the sucrose-loading capability in Jishu 26 TRs were stronger than that in Xushu 32 and Ningzishu 1 TRs. Moreover, IbA-INV3, IbAGPS1, IbAGPS2, IbGBSSI and IbSBEII play important roles in different drought-tolerant cultivars under drought stress.

Case Report: Chimeric Antigen Receptor T Cells Induced Late Severe Cytokine Release Syndrome.

Background: Severe cytokine release syndrome (sCRS) has emerged as an adverse complication in the early period of chimeric antigen receptor T cell (CART) therapy, while whether sCRS occurs in the late period remains unknown. Here, we reported two patients with late sCRS. Case Presentation: Case 1 was a 34-year-old female with refractory Philadelphia chromosome-positive B cell acute lymphoblastic leukemia. She achieved complete remission (CR) but experienced grade III CRS and hemophagocytic lymphohistiocytosis (HLH) 41 days after CD19-targeted CART (CART19) cells and CD22-targeted CART (CART22) cells infusion. Ineffective to tocilizumab and HLH-94 protocol (dexamethasone and etoposide), she died of a cerebral hemorrhage on day 55 after CART therapy. Case 2 was a 38-year-old male with IgG kappa multiple myeloma. He received autologous BCMA-targeted CART (BCMA-CART) therapy 4 months after HLA-matched sibling (sister) donor transplantation and developed grade III CRS 163 days after CART administration, characterized by fever, hypotension, and skin lesions. Effective to methylprednisolone and tocilizumab, his clinical response persisted for over 6.0 months. Conclusion: Severe CRS could occur in the late period after CART therapy as re-expansion of CART cells possessed the potential risk for late sCRS.

A Hydrogen-Free Approach for Activating an Fe Catalyst Using Trace Amounts of Noble Metals and Confinement into Nanoparticles.

Metallic iron (Fe) represents an exceptionally active catalyst, as shown in its use in the Haber-Bosch process to dissociate nitrogen molecules; however, the ease of corrosion by oxidation limits its usage. Hence, in most applications using metallic Fe catalysts, hydrogen is a necessary reactant. We report a novel hydrogen-free approach to fabricating reduced, highly active, and corrosion-resistive Fe-based catalysts using trace levels of noble metals (NMs) such as Ir, Rh, and Pt confined in the nanoparticle (NP). X-ray photoelectron spectroscopy (XPS) revealed that as little as ∼0.3 atom % was sufficient to induce the reduction of Fe. Extensive XPS analysis showed that the reduced NM atoms segregated to the NP surface and reduced the surrounding Fe atoms. We demonstrated the catalytic activity of the nanoparticles by the efficient synthesis of submillimeter tall, vertically aligned, and mainly double-walled carbon nanotube arrays using a completely hydrogen-free chemical vapor deposition process.

CAR NK-92 cells targeting DLL3 kill effectively small cell lung cancer cells in vitro and in vivo.

Small cell lung cancer (SCLC) is characterized by a high relapse rate, drug tolerance, and limited treatment choices. Chimeric antigen receptor (CAR)-modified NK cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential applications have not been explored in SCLC. Delta-like ligand 3 (DLL3) has been reported to be overexpressed in SCLC and may be a rational target for CAR NK immunotherapy. In this study, we developed DLL3-specific NK-92 cells and explored their potential in the treatment of SCLC. A coculture of DLL3+ SCLC cell lines with DLL3-CAR NK-92 cells exhibited significant in vitro cytotoxicity and cytokine production. DLL3-CAR NK-92 cells induced tumor regression in an H446-derived pulmonary metastasis tumor model under a good safety threshold. The potent antitumor activities of DLL3-CAR NK-92 cells were observed in subcutaneous tumor models of SCLC. Moreover, obvious tumor-infiltrated DLL3-CAR NK-92 cells were detected in DLL3+ SCLC xenografts. These findings indicate that DLL3-CAR NK-92 cells might be a potential strategy for the treatment of SCLC.

Surpassing the diffraction limit using an external aperture modulation subsystem and related deep learning method.

The resolution of conventional imaging systems is inherently restricted by the diffraction limit. To surpass this diffraction barrier, a scheme using an external aperture modulation subsystem (EAMS) and related deep learning network (DLN) is presented in this paper. The EAMS facilitates the realization of various image acquisition strategies and related DLN architectures. In the specific scenario of 3-aperture modulation strategy, the capabilities of this approach are validated both in numerical simulations and experiments. The results show that both the resolution enhancement ability and the image fidelity can be improved by just adding one label data. This framework proposed here provides a more general way to further explore the ability of DLN-based method to surpass the diffraction limit, and permits a rapid data acquisition that enables new opportunities for the training data collection and further super resolution imaging of label-free moving objects, such as living cells.

Development of mesothelin-specific CAR NK-92 cells for the treatment of gastric cancer.

Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR NK cell efficacy. It has been reported that mesothelin (MSLN) may be an ideal immunotherapy target for gastric cancer. However, the feasibility of using anti-MSLN CAR NK cells to treat gastric cancer remains to be studied. Methods: MSLN expression in primary human gastric cancer, normal tissues and cell lines were detected. MSLN and CD19 targeted CAR NK-92 (MSLN- and CD19-CAR NK) cells were constructed, purified and verified. N87, MKN-28, AGS and Huh-7 cells expressing the GFP and luciferase genes were transduced. Cell- and patient-derived xenograft (PDX) were established via NSG mice. The ability of MSLN-CAR NK cells to kill MSLN-positive gastric cancer cells were evaluated in vitro and in vivo. Results: MSLN-CAR NK cells can specifically kill MSLN-positive gastric cancer cells (N87, MKN-28 and AGS), rather than MSLN negative cell (Huh-7), in vitro. Moreover, compared with parental NK-92 cells and CD19-CAR NK cells, stronger cytokine secretions were secreted in MSLN-CAR NK cells cocultured with N87, MKN-28 and AGS. Furthermore, MSLN-CAR NK cells can effectively eliminate gastric cancer cells in both subcutaneous and intraperitoneal tumor models. They could also significantly prolong the survival of intraperitoneally tumor-bearing mice. More importantly, the potent antitumor effect and considerable NK cell infiltration were observed in the patient-derived xenograft treated with MSLN-CAR NK cells, which further warranted the therapeutic effects of MSLN-CAR NK cells to treat gastric cancer. Conclusion: These results demonstrate that MSLN-CAR NK cells possess strong antitumor activity and represent a promising therapeutic approach to gastric cancer.

Preparation of Large Conjugated Polybenzimidazole Fluorescent Materials and Their Application in Metal Ion Detection.

A new type of conjugated polybenzimidazole (CPBI) was synthesized through a simple polycondensation reaction without metal catalysis, and N-alkylation modification was carried out to solve the problems of solubility and fluorescence properties. A series of nano-microsphere polymers CPBIn with large conjugation, good solubility, and strong fluorescence has been successfully used as "turn-off" fluorescent probes for the first time. The results show that, under suitable N-alkylation conditions, the obtained CPBIn can be used as a highly sensitive and selective fluorescent probe for the detection of Cu2+ and Zn2+ at the same time, and their detection limits are both nM levels. In addition, CPBI2 can be designed as an ultra-sensitive IMPLICATION logic gate at the molecular level, cyclically detecting Cu2+. With the test paper containing CPBI2, easy and quick on-site detection can be achieved. This research provides a new idea for the brief synthesis of multifunctional materials.

[Effect of trimetazidine on cardiac function and exercise tolerance in hypertension patients with diabetic].

OBJECTIVE: To determine the effect of trimetazidine on cardiac function and exercise tolerance in primary hypertension patients with type 2 diabetic. METHODS: In this randomized, double-blind, placebo-controlled prospective study, 60 primary hypertensive patients with diabetic were equally assigned into two groups, patients received trimetazidine (20 mg, 3 times a day) or placebo for 1 year. Echocardiography, cardiopulmonary exercise testing were performed; and the plasma N terminal pro B type natriuretic peptide (NT-ProBNP), hr-CRP, TNF-α, angiotensin Ⅱ and endothelin concentration were determined before and after treatment. RESULTS: In trimetazidine group, the left ventricular mass index, the mitral flow velocity E wave to A wave ratio (E/A), the peak early diastolic velocity (VE) to late diastolic velocity (VA) ratio (VE/VA) and the peak systolic velocity (Vs) were significantly improved, the plasma NT-ProBNP level was significantly decreased, and the exercise time, metabolic equivalent, maximal oxygen uptake and anaerobic threshold were significantly increased (all P<0.05); plasma concentration of hr-CRP, TNF-α, angiotensin Ⅱ and endothelin were significantly reduced after trimetazidine treatment, compared with baseline (all P<0.05) and with placebo (all P<0.05). There were no significant differences in any of above parameters after treatment in placebo group (all P>0.05). No severe adverse reaction was observed in both groups. CONCLUSIONS: For patients with both hypertension and diabetes, trimetazidine can improve cardiac function and increase exercise tolerance.

Super-resolution imaging via aperture modulation and intensity extrapolation.

High-resolution telescopic imaging is of great importance in astronomy. Compared to the complexity and huge cost of constructing extremely-large telescopes, super-resolution technique which breaks the diffraction limit of the imaging system can enhance the spatial resolution with compact setup and low cost. In this paper, a novel super-resolution telescopic imaging method based on aperture modulation and intensity extrapolation is demonstrated, with both simulated and experimental studies performed. The simulation results show that the method can enhance the resolving power of a diffraction-limited telescopic imaging system by >5 times in noise-free case, and the improvement still reaches ~1.8 times with a signal-to-noise ratio of only ~10. The preliminary experimental results show a resolution enhancement of ~1.36 times for the limitations of the experimental setup. Better performance is possible with the images for reconstruction denoised and registered more precisely. The method is also useful in wide-field microscopy.

Noninvasive, label-free, three-dimensional imaging of melanoma with confocal photothermal microscopy: Differentiate malignant melanoma from benign tumor tissue.

Skin cancer is one of the most common cancers. Melanoma accounts for less than 2% of skin cancer cases but causes a large majority of skin cancer deaths. Early detection of malignant melanoma remains the key factor in saving lives. However, the melanoma diagnosis is still clinically challenging. Here, we developed a confocal photothermal microscope for noninvasive, label-free, three-dimensional imaging of melanoma. The axial resolution of confocal photothermal microscope is ~3 times higher than that of commonly used photothermal microscope. Three-dimensional microscopic distribution of melanin in pigmented lesions of mouse skin is obtained directly with this setup. Classic morphometric and fractal analysis of sixteen 3D images (eight for benign melanoma and eight for malignant) showed a capability of pathology of melanoma: melanin density and size become larger during the melanoma growth, and the melanin distribution also becomes more chaotic and unregulated. The results suggested new options for monitoring the melanoma growth and also for the melanoma diagnosis.

Mechanism study of 2-D laser array generation in a YAG crystal plate.

We have reproduced the process of two-dimensional array generation by using two crossing laser beams in a YAG crystal plate based on numerical simulation considering cross-phase modulation (XPM) and self-focusing. Furthermore, we come to the conclusion that both XPM and the cylindrical symmetry breaking in the initial beam profile contributes to the generation of two-dimensional array. In addition, we have studied the threshold input laser beam power for the two crossing beams splitting in a YAG crystal plate. Our study could be valuable in various applications, such as 2-D all-optical switching devices or multicolor pump-probe experiments.

Biological imaging with nonlinear photothermal microscopy using a compact supercontinuum fiber laser source.

Nonlinear photothermal microscopy is applied in the imaging of biological tissues stained with chlorophyll and hematoxylin. Experimental results show that this type of organic molecules, which absorb light but transform dominant part of the absorbed energy into heat, may be ideal probes for photothermal imaging without photochemical toxicity. Picosecond pump and probe pulses, with central wavelengths of 488 and 632 nm, respectively, are spectrally filtered from a compact supercontinuum fiber laser source. Based on the light source, a compact and sensitive super-resolution imaging system is constructed. Further more, the imaging system is much less affected by thermal blurring than photothermal microscopes with continuous-wave light sources. The spatial resolution of nonlinear photothermal microscopy is ~ 188 nm. It is ~ 23% higher than commonly utilized linear photothermal microscopy experimentally and ~43% than conventional optical microscopy theoretically. The nonlinear photothermal imaging technology can be used in the evaluation of biological tissues with high-resolution and contrast.

Label-free imaging of melanoma with nonlinear photothermal microscopy.

Nonlinear photothermal microscopy, in which the intensity of the pump heating beam is modulated at f and the photothermal signal is extracted from the probe beam with a lock-in amplifier referred to 2f, is applied to the imaging of mouse melanoma without any staining. The pump and probe pulses, with central wavelengths of 488 and 632 nm, and a pulse duration of ∼100 ps, are filtered from a compact commercial supercontinuum fiber laser source. An auto-balanced detector is applied to accumulate the signal and remove the laser noise of the probe. The spatial resolution of the nonlinear photothermal imaging is enhanced by ∼18% in both theoretical calculations and experiments, compared with a linear photothermal mechanism, and the resolution enhancement is theoretically ∼42% compared with conventional optical microscopy. This imaging technique shows possibilities for the clinical evaluation of melanoma with a high contrast and spatial resolution.

Generation of sub-20-fs deep-ultraviolet pulses by using chirped-pulse four-wave mixing in CaF2 plate.

Sub-20-fs deep ultraviolet (DUV) pulses are generated by using nondegenerate, chirped-pulse four-wave mixing of the fundamental and second-harmonic pulses from a commercial Ti:sapphire amplifier in a CaF(2) plate. The energy of the DUV pulses is 3.8 µJ, with a conversion efficiency from total pump energy to DUV of ~3.8%. The DUV pulse is compressed using a pre-chirp, introduced via a fused silica window in the fundamental beam. The central wavelength of the DUV spectrum can be tuned from 257 to 277 nm by adjusting the cross angle between the two pump beams. The spectrum can reach a width of 16.8 nm, which can support a pulse duration of 8.7 fs.

Pulse width tunable passively mode-locked Nd:YVO4 laser based on hybrid laser gain medium locations.

A pulse width tunable passively mode-locked laser with a wavelength of 1,064 nm and two Nd:YVO(4) crystals located in asymmetric positions is demonstrated. By adjusting the pump power of the crystals, the pulse width can be continuously tuned from 8.8 to 20.3 ps at a stable mode-locked repetition rate of 122 MHz. A theoretical model is proposed to describe the experiment results phenomenologically. In this system, a maximum output power of 4.44 W is achieved with a pump of 13.68 W, corresponding to an optical-to-optical efficiency of 32.5%. The beam quality factor, M(2), is found to be M(2)(x) = 1.15 and M(2)(y) = 1.13 in the orthogonal directions at an output power of 3.2 W.