IFNγ at the early stage induced after cryo-thermal therapy maintains CD4+ Th1-prone differentiation, leading to long-term antitumor immunity.

Introduction: Recently, more and more research illustrated the importance of inducing CD4+ T helper type (Th)-1 dominant immunity for the success of tumor immunotherapy. Our prior studies revealed the crucial role of CD4+ Th1 cells in orchestrating systemic and durable antitumor immunity, which contributes to the satisfactory outcomes of the novel cryo-thermal therapy in the B16F10 tumor model. However, the mechanism for maintaining the cryo-thermal therapy-mediated durable CD4+ Th1-dominant response remains uncovered. Additionally, cryo-thermal-induced early-stage CD4+ Th1-dominant T cell response showed a correlation with the favorable prognosis in patients with colorectal cancer liver metastasis (CRCLM). We hypothesized that CD4+ Th1-dominant differentiation induced during the early stage post cryo-thermal therapy would affect the balance of CD4+ subsets at the late phase. Methods: To understand the role of interferon (IFN)-γ, the major effector of Th1 subsets, in maintaining long-term CD4+ Th1-prone polarization, B16F10 melanoma model was established in this study and a monoclonal antibody was used at the early stage post cryo-thermal therapy for interferon (IFN)-γ signaling blockade, and the influence on the phenotypic and functional change of immune cells was evaluated. Results: IFNγ at the early stage after cryo-thermal therapy maintained long-lasting CD4+ Th1-prone immunity by directly controlling Th17, Tfh, and Tregs polarization, leading to the hyperactivation of Myeloid-derived suppressor cells (MDSCs) represented by abundant interleukin (IL)-1ß generation, and thereby further amplifying Th1 response. Discussion: Our finding emphasized the key role of early-phase IFNγ abundance post cryo-thermal therapy, which could be a biomarker for better prognosis after cryo-thermal therapy.

Phenotypic and genomic insights into mutant with high nattokinase-producing activity induced by carbon ion beam irradiation of Bacillus subtilis.

Nattokinase (NK) is found in fermented foods and has high fibrinolytic activity, which makes it promising for biological applications. In this study, a mutant strain (Bacillus subtilis ZT-S1, 5529.56 ± 183.59 U/mL) with high NK-producing activity was obtained using 12C6+ heavy ion beam mutagenesis for the first time. The surface morphology of B. subtilis is also altered by changes in functional groups caused by heavy ion beams. Furthermore, B. subtilis ZT-S1 required more carbon and nitrogen sources and reached stabilization phase later. Comparative genome analysis revealed that most of the mutant implicated genes (oppA, appA, kinA, spoIIP) were related to spore formation. And the affected rpoA is related to the synthesis of the NK-coding gene aprE. In addition, the B. subtilis ZT-S1 obtained by mutagenesis had good genetic stability. This study further explores the factors affecting NK activity and provides a promising microbial resource for NK production in commercial applications.

Natural Killer Cells Reprogram Myeloid-Derived Suppressor Cells to Induce TNF-α Release via NKG2D-Ligand Interaction after Cryo-Thermal Therapy.

In our previous studies, a novel cryothermal therapy (CTT) was developed to induce systemic long-term anti-tumor immunity. Natural killer (NK) cells were found to play an important role in CTT-induced long-term immune-mediated tumor control at the late stage after CTT, but the underlying mechanism is unclear. Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that have potent immunosuppressive effects on T cells and weaken the long-term benefits of immunotherapy. Consequently, overcoming MDSC immunosuppression is essential for maintaining the long-term efficacy of immunotherapy. In this study, we revealed that NK cells considerably diminish MDSC accumulation at the late stage after CTT, boost T cell production, increase T cell activation, and promote MDSC maturation, culminating in Th1-dominant CD4+ T cell differentiation and enhancing NK and CD8+ T cell cytotoxicity. Additionally, NK cells activate ERK signaling in MDSCs through NKG2D-ligand interaction to increase the activity of tumor necrosis factor (TNF)-α converting enzyme (TACE)-cleaved membrane TNF-α. Furthermore, Increased TACE activity releases more soluble TNF-α from MDSCs to promote MDSC maturation. In our studies, we propose a novel mechanism by which NK cells can overcome MDSC-induced immunosuppression and maintain CTT-induced persistent anti-tumor immunity, providing a prospective therapeutic option to improve the performance of cancer immunotherapy.

An acute gastric volvulus in a child with congenital left diaphragmatic hernia: a case report.

BACKGROUND: Acute complete gastric volvulus is a rare and life-threatening disease, which is prone to gastric wall ischemia, perforation, and necrosis. If it is not treated by surgery in time, the mortality rate can range from 30 to 50%. Clinical presentations of acute gastric volvulus are atypical and often mimic other abdominal conditions such as gastritis, gastroesophageal reflux, gastric dilation, and pancreatitis. Imaging studies are crucial for diagnosis, with barium meal fluoroscopy being the primary modality for diagnosing gastric volvulus. Cases of acute gastric volvulus diagnosed by ultrasound are rarely reported. CASE PRESENTATION: We reported a rare case of acute gastric volvulus in a 4-year-old Chinese girl who presented with vomiting and abdominal pain. Ultrasound examination revealed the "whirlpool sign" in the cardia region, raising suspicion of gastric volvulus. Diagnosis was confirmed by X-ray barium meal fluoroscopy, which indicated left-sided diaphragmatic hernia and obstruction at the cardia region. Surgical intervention confirmed our suspicion of acute complete gastric volvulus combined with diaphragmatic hernia. CONCLUSION: In this case, we reported an instance of acute complete gastric volvulus. Ultrasound revealed a "whirlpool sign" in the cardia, which is likely to be a key sign for the diagnosis of complete gastric volvulus.

Tetraphenylethylene-Based Hydrogen-Bonded Organic Frameworks (HOFs) with Brilliant Fluorescence.

By synergistically employing four key strategies: (I) introducing tetraphenylethylene groups as the central core unit with aggregation-induced emission (AIE) properties, (II) optimizing the π-conjugated length by extending the building block branches, (III) incorporating flexible groups containing ethylenic bonds, and (IV) applying crystal engineering to attain dense stacking mode and highly twisty conformation, we successfully synthesized a series of hydrogen-bonded organic frameworks (HOFs) exhibiting exceptional one/two-photon excited fluorescence. Notably, when utilizing the fluorescently superior building block L2, HOF-LIFM-7 and HOF-LIFM-8 exhibiting high quantum yields (QY) of 82.1 % and 77.1 %, and ultrahigh two-photon absorption (TPA) cross-sections of 148959.5 GM and 123901.1 GM were achieved. These materials were successfully employed in one and two-photon excited lysosome-targeting cellular imaging. It is believed that this strategy, combining building block optimization and crystal engineering, holds significant potential for guiding the development of outstanding fluorescent HOF materials.

Sequential pre-disinfection with chlorhexidine and alcohol reduces periprosthetic joint infection after primary knee arthroplasty: A case-control study.

A retrospective case-control study was conducted to assess whether patients who underwent sequential preoperative disinfection before primary total knee or unicompartmental arthroplasty had a lower rate of postoperative infection than those who did not. In our study, 1025 patients who underwent total knee or unicompartmental arthroplasty at 2 medical centers between September 1, 2020, and August 31, 2021, were enrolled. Statistical analysis was performed for 976 cases, including 966 and 10 uninfected and infected cases, respectively. All patients were followed up for 1-year. Data analysis was performed by binary logistic regression and adjusted for 2 confounding factors: general anesthesia and rheumatoid arthritis. IBM SPSS for Windows (version 25.0; IBM Co., Armonk, NY) software was used to perform all statistical analyses. During the study period, of the 976 patients, 10 cases of infections were detected. Sequential pre-disinfection (adjusted odds ratio 0.14, 95% confidence interval: 0.03-0.54, P = .005) could reduce the incidence of infection. Based on the results of this study, bathing the whole lower limb with 2% chlorhexidine on the night before surgery followed by 70% alcohol application 1 hour before surgery is effective for preventing periprosthetic joint infection during primary total knee or unicompartmental arthroplasty.

Sequential self-assembly of calix[4]resorcinarene-based heterobimetallic Cd8Pt8 nano-Saturn complexes.

A rational molecular design strategy is introduced for selective metal-ligand coordination, enabling the quantitative self-assembly of heterobimetallic nano-Saturn complexes. During the sequential multicomponent self-assembly, the CdII ions and organometallic trans-PtII motifs demonstrate preferential binding to specific ligands. The pre-designed directive interactions allow for precise control over the structural characteristics.

An intussusception caused by a rare transverse colon lipoma: Case report.

INTRODUCTION: Intestinal lipoma is a rare benign tumor with a reported incidence of 0.2 % to 4.4 %. It is seen mainly in patients aged 50 to 70 years. Intestinal lipoma as a pathological lead point of intussusception is rare. There are few reports of colic lipoma in children. PRESENTATION OF CASE: We reported a 7-year-old girl with a 4-year history of intermittent abdominal pain. Ultrasound examination showed a homogeneous hyperechoic mass near the distal transverse colon, which was similar to the surrounding lipid tissue. Histopathological examination confirmed the diagnosis of intestinal lipoma. DISCUSSION: Colonic lipoma is very rare in children. If intussusception occurs repeatedly, or if it occurs in older children, we should consider the presence of pathological lead point. Early diagnosis and immediate surgical intervention are the key factors to a successful outcome. CONCLUSION: In this case we report a pediatric case of intussusception secondary to colonic lipoma, and describe imaging and pathologic signs suggestive of intestinal lipoma.

One/Two-Photon-Excited ESIPT-Attributed Coordination Polymers with Wide Temperature Range and Color-Tunable Long Persistent Luminescence.

The multiple metastable excited states provided by excited-state intramolecular proton transfer (ESIPT) molecules are beneficial to bring temperature-dependent and color-tunable long persistent luminescence (LPL). Meanwhile, ESIPT molecules are intrinsically suitable to be modulated as D-π-A structure to obtain both one/two-photon excitation and LPL emission simultaneously. Herein, we report the rational design of a dynamic CdII coordination polymer (LIFM-106) from ESIPT ligand to achieve the above goals. By comparing LIFM-106 with the counterparts, we established a temperature-regulated competitive relationship between singlet excimer and triplet LPL emission. The optimization of ligand aggregation mode effectively boost the competitiveness of the latter. In result, LIFM-106 shows outstanding one/two-photon excited LPL performance with wide temperature range (100-380 K) and tunable color (green to red). The multichannel radiation process was further elucidated by transient absorption and theoretical calculations, benefiting for the application in anti-counterfeiting systems.

Three-dimensional femur morphology analysis for the optimal location of subtrochanteric osteotomy with an implanted Wagner cone stem in total hip arthroplasty for Crowe type IV developmental dysplasia of the hip.

BACKGROUND: This study aimed to accurately evaluate the matching of proximal and distal femoral segments and fitting of the femur-femoral stem in patients with Crowe type IV developmental dysplasia of the hip (DDH) who have undergone subtrochanteric osteotomy at different locations with an implanted Wagner cone stem to improve the rate of the bone union at the osteotomy site. METHODS: Three-dimensional femur morphology of 40 patients with Crowe type IV DDH was evaluated at each cross-section to determine the femoral cortical bone area. This study focused on five osteotomy lengths (2.5, 3, 3.5, 4, and 4.5 cm). The overlapped area between the proximal and distal cortical bone segments was defined as the contact area (S, mm2), and the contact area to distal cortical bone area ratio was defined as the coincidence rate (R). Three indicators were used to evaluate the matching and fitting of the osteotomy sites with the implanted Wagner cone stems: (1) higher S and R between the proximal and distal segments; (2) the effective fixation length of the femoral stem at the distal segments being at least 1.5 cm; and (3) osteotomy did not involve the isthmus. RESULTS: In all groups, S significantly decreased in the two proximal levels above the 0.5 cm level below the lesser trochanter (LT) compared with those below this level. In comparison, at osteotomy lengths from 2.5 to 4 cm, R significantly decreased in the three proximal levels. The optimal osteotomy levels ranged from 1.5 and 2.5 cm below the LT for an appropriately sized stem. CONCLUSIONS: Subtrochanteric osteotomy at the optimal level not only ensures fitting of the femur-femoral stem but also meets the requirements of a higher S and R to ensure adequate reduction and stabilization at the osteotomy site, which may contribute to the bone union. Although the optimal osteotomy level varies with the size of the femoral stem and the length of the subtrochanteric osteotomy, the optimal osteotomy levels for an appropriately sized Wagner cone femoral stem implantation range from 1.5 to 2.5 cm below the LT.

Study on the Performance and Mechanism of Cement Solidified Desulfurization Manganese Residue.

Desulfurized manganese residue (DMR) is an industrial solid residue produced by high-temperature and high-pressure desulfurization calcination of electrolytic manganese residue (EMR). DMR not only occupies land resources but also easily causes heavy metal pollution in soil, surface water, and groundwater. Therefore, it is necessary to treat the DMR safely and effectively so that it can be used as a resource. In this paper, Ordinary Portland cement (P.O 42.5) was used as a curing agent to treat DMR harmlessly. The effects of cement content and DMR particle size on flexural strength, compressive strength, and leaching toxicity of a cement-DMR solidified body were studied. The phase composition and microscopic morphology of the solidified body were analyzed by XRD, SEM, and EDS, and the mechanism of cement-DMR solidification was discussed. The results show that the flexural strength and compressive strength of a cement-DMR solidified body can be significantly improved by increasing the cement content to 80 mesh particle size. When the cement content is 30%, the DMR particle size has a great influence on the strength of the solidified body. When the DMR particle size is 4 mesh, the DMR particles will form stress concentration points in the solidified body and reduce its strength. In the DMR leaching solution, the leaching concentration of Mn is 2.8 mg/L, and the solidification rate of Mn in the cement-DMR solidified body with 10% cement content can reach 99.8%. The results of XRD, SEM, and EDS showed that quartz (SiO2) and gypsum dihydrate (CaSO4·2H2O) were the main phases in the raw slag. Quartz and gypsum dihydrate could form ettringite (AFt) in the alkaline environment provided by cement. Mn was finally solidified by MnO2, and Mn could be solidified in C-S-H gel by isomorphic replacement.

Combining Cryo-Thermal Therapy with Anti-IL-6 Treatment Promoted the Maturation of MDSCs to Induce Long-Term Survival in a Mouse Model of Breast Cancer.

Immunosuppression plays a significant role in tumor recurrence and metastasis, ultimately causing poor survival outcomes. Overcoming immunosuppression and stimulating durable antitumor immunity are essential for tumor treatment. In our previous study, a novel cryo-thermal therapy involving liquid nitrogen freezing and radiofrequency heating could reduce the proportion of Myeloid-derived suppressor cells (MDSCs), but the remaining MDSCs produced IL-6 by the NF-κB pathway, resulting in an impaired therapeutic effect. Therefore, here we combined cryo-thermal therapy with anti-IL-6 treatment to target the MDSC-dominant immunosuppressive environment, thereby optimizing the efficacy of cryo-thermal therapy. We found that combinational treatment significantly increased the long-term survival rate of breast cancer-bearing mice. Mechanistic investigation revealed that combination therapy was capable of reducing the proportion of MDSCs in the spleen and blood while promoting their maturation, which resulted in increased Th1-dominant CD4+ T-cell differentiation and enhancement of CD8+ T-mediated tumor killing. In addition, CD4+ Th1 cells promoted mature MDSCs to produce IL-7 through IFN-γ, indirectly contributing to the maintenance of Th1-dominant antitumor immunity in a positive feedback loop. Our work suggests an attractive immunotherapeutic strategy targeting the MDSC-dominant immunosuppressive environment, which would offer exciting opportunities for highly immunosuppressive and unresectable tumors in the clinic.

A 5.3 nm giant metal-organic cage and its supramolecular gel for the formation of dye molecular ionic pairs.

A terpyridine-based supramolecular cage was successfully synthesized by the self-assembly of a hexapodal metal-organic ligand with Zn2+. This metallo-cage exhibited two large parallel planes on the top and bottom with diameters close to 6 nm and a face-to-face distance close to 3.5 nm, thus possessing a large cavity. Electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR), two-dimensional nuclear Overhauser (2D-NOESY), and diffusion-ordered (DOSY) spectroscopies as well as transmission electron microscopy (TEM) and atomic force microscopy (AFM) measurements, unambiguously supported the formation of a supramolecular cage. Furthermore, the corresponding metal-organic gel was felicitously prepared in CH3CN/H2O and displayed good adsorption performance for dye molecules.

[Propensity score-matched study of uni-condylar arthroplasty in elderly patients with knee osteoarthritis].

OBJECTIVE: To investigate the clinical efficacy of unicompartmental knee arthroplasty (UKA) in the treatment of knee osteoarthritis in patients over 75 years old. METHODS: The clinical efficacy of primary fixed platform UKA in patients with osteoarthritis, was retrospectively analyzed from October 2014 to November 2020. Age, body mass index (BMI), range of motion (ROM), preoperative joint function score, the quality of life score and other preoperative indicators were measured by propensity score matching (PSM). The patients were divided into elderly group (≥75 years old) and control group (<75 years old). Oxford knee score(OKS), Western Ontario McMaster Universities osteoarthritis index(WOMAC), Short Form-12 including physical component summary (PCS), mental component summary(MCS), minimal clinically important difference(MCID ) and clinical complications were evaluated preoperatively and postoperatively. RESULTS: A total of 514 patients were analyzed, 428 patients fulfilled the inclusion criteria. A propensity-score matching study was conducted to eliminate confounding factors. After 1∶2 propensity match, there were 84 patients in elderly group (≥75 years), age ranged from 75 to 88 years old, with an average of (78.79±3.08) years old, and 168 patients in control group (<75 years), age ranged from 47 to 74 years old, with an average of (64.10±5.96)years old. The follow-up duration of two groups ranged from 12 to 84 months with an average of (29.35±16.52) months in elderly group, and 12 to 85 months with an average of (31.83±17.34) months in control group. There was only significant difference in age between the elderly and control groups preoperatively (P<0.01). Postoperatively, the elderly group showed significantly higher WOMAC (P<0.01) and lower SF-12 PCS scores (P<0.01) as compared to the control group. There was no significant difference between the elderly group and the control group in knee range of motion, OKS and the proportion of each scoring system reaching the minimum clinical difference value (P>0.05). In the aspect of preperative complications, the elderly group exhibited more surgical site complications and postoperative delirium compared to control group(P<0.05). The differences in other indicators including deep vein thrombosis, acute urinary retention, cardiovascular events, cerebrovascular events and radiolucent lines around prothesis were not statistically significant(P>0.05). CONCLUSION: UKA in the treatment of elderly patients over 75 years old with knee osteoarthritis was safe and feasible, and could obtain satisfactory short-term efficacy.

Activated NK cells reprogram MDSCs via NKG2D-NKG2DL and IFN-γ to modulate antitumor T-cell response after cryo-thermal therapy.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) can potently inhibit T-cell activity, promote growth and metastasis of tumor and contribute to resistance to immunotherapy. Targeting MDSCs to alleviate their protumor functions and immunosuppressive activities is intimately associated with cancer immunotherapy. Natural killer (NK) cells can engage in crosstalk with multiple myeloid cells to alter adaptive immune responses, triggering T-cell immunity. However, whether the NK-cell-MDSC interaction can modulate the T-cell immune response requires further study. Cryo-thermal therapy could induce the maturation of MDSCs by creating an acute inflammatory environment to elicit a CD4+ Th1-dominant immune response, but the mechanism regulating this process remains unclear. METHODS: NK cells were depleted and NKG2D was blocked with monoclonal antibodies in vivo. MDSCs, NK cells and T cells were assessed by flow cytometry and isolated by magnetic-activated cell sorting (MACS). MDSCs and NK cells were cocultured with T cells to determine their immunological function. The transcriptional profiles of MDSCs were measured by qRT-PCR and RNA-sequencing. Isolated NK cells and MDSCs by MACS were cocultured to study the viability and maturation of MDSCs regulated by NK cells. TIMER was used to comprehensively examine the immunological, clinical, and genomic features of tumors. RESULTS: NK-cell activation after cryo-thermal therapy decreased MDSC accumulation and reprogrammed immunosuppressive MDSCs toward a mature phenotype to promote T cell antitumor immunity. Furthermore, we discovered that NK cells could kill MDSCs via the NKG2D-NKG2DL axis and promote MDSC maturation by interferon gamma (IFN-γ) in response to NKG2D. In addition, CD4+ Th1-dominant antitumor immune response was dependent on NKG2D, which promoted the major histocompatibility complex Ⅱ pathway of MDSCs. High activated NK-cell infiltration and NKG2D level in tumors were positively correlated with better clinical outcomes. CONCLUSIONS: Cryo-thermal therapy induces effective CD4+ Th1-dominant antitumor immunity by activating NK cells to reprogram MDSCs, providing a promising therapeutic strategy for cancer immunotherapy.

Slight compositional variation-induced structural disorder-to-order transition enables fast Na+ storage in layered transition metal oxides.

The omnipresent Na+/vacancy orderings change substantially with the composition that inevitably actuate the ionic diffusion in rechargeable batteries. Therefore, it may hold the key to the electrode design with high rate capability. Herein, the influence of Na+/vacancy ordering on Na+ mobility is demonstrated firstly through a comparative investigation in P2-Na2/3Ni1/3Mn2/3O2 and P2-Na2/3Ni0.3Mn0.7O2. The large zigzag Na+/vacancy intralayer ordering is found to accelerate Na+ migration in P2-type Na2/3Ni1/3Mn2/3O2. By theoretical simulations, it is revealed that the Na+ ordering enables the P2-type Na2/3Ni1/3Mn2/3O2 with higher diffusivities and lower activation energies of 200 meV with respect to the P3 one. The quantifying diffusional analysis further prove that the higher probability of the concerted Na+ ionic diffusion occurs in P2-type Na2/3Ni1/3Mn2/3O2 due to the appropriate ratio of high energy ordered Na ions (Naf) occupation. As a result, the interplay between the Na+/vacancy ordering and Na+ kinetic is well understood in P2-type layered cathodes.

Combining all-trans retinoid acid treatment targeting myeloid-derived suppressive cells with cryo-thermal therapy enhances antitumor immunity in breast cancer.

Targeting myeloid-derived suppressive cells (MDSCs) has been considered a potential strategy in tumor therapy. However, a single drug targeting MDSCs remains a challenge in the clinic. An increasing number of studies have shown that combination agents targeting MDSCs and immunotherapy may provide exciting new insights and avenues to explore in tumor therapy. In our previous study, a novel cryo-thermal therapy was developed for metastatic tumors that systematically activate innate and adaptive immunity. Moreover, cryo-thermal therapy was shown to dramatically decrease the levels of MDSCs and induce their differentiation toward potent antigen-presenting cells. However, the therapeutic effects of cryo-thermal therapy on the 4T1 mouse breast cancer model were still not satisfactory because of the high level of MDSCs before and after treatment. Therefore, in this study, we combined cryo-thermal therapy with all-trans retinoid acid (ATRA), a small molecule drug that can induce the inflammatory differentiation of MDSCs. We found that combination therapy notably upregulated the long-term survival rate of mice. Mechanically, combination therapy promoted the phenotype and functional maturation of MDSCs, efficiently decreasing suppressive molecule expression and inhibiting glutamine and fatty acid metabolism. Moreover, MDSCs at an early stage after combination therapy significantly decreased the proportions of Th2 and Treg subsets, which eventually resulted in Th1-dominant CD4+ T-cell differentiation, as well as enhanced cytotoxicity of CD8+ T cells and natural killer cells at the late stage. This study suggests a potential therapeutic strategy for combination ATRA treatment targeting MDSCs with cryo-thermal therapy to overcome the resistance of MDSC-induced immunosuppression in the clinic.

One and Two-Photon Excited Fluorescence Optimization of Metal-Organic Frameworks with Symmetry-Reduced AIEgen-Ligand.

By designing a tetraphenylethylene (TPE)-based AIEgen-ligand with reduced symmetry, we obtained two alkaline-earth metal-based MOFs (LIFM-102 and LIFM-103) with dense packing structures and low porosity as proved by single-crystal X-ray diffraction and CO2 sorption data. Excitingly, the desolvated MOFs with rigid environment and reduced lattice free solvent exhibit high quantum yields (QY, 64.9 % and 79.4 %) and excellent two-photon excited photoluminescence (TPA cross-sections, 2946.6 GM and 2899.0 GM), while maintaining the external-stimuli-responsive properties suitable for anticounterfeit fields. The effect of ligand conformation was validated by comparing the structure and fluorescence properties of the samples before and after desolvation and further verified by theoretical calculations. This work expands the study on TPE-cored materials to symmetry-reduced ligand and might bring forward novel structures and excellent photoluminescent properties in the future.

A New Approach for Target Capability Assessment and Selection in Complex Situations.

In modern information warfare, medium and long-range weapons with high strike precision are often used to ensure stable, accurate, and ruthless conditions. However, the target system often has multiple target units and which target units to specifically attack becomes the primary issue. This study constructs a target combat system network based on the complex network theory and maximum entropy principle, establishes a key target selection model based on this network, and then determines the use of medium and long-range weapons to strike the key target unit in the enemy combat system network. The key target selection model consists of four parts. The first is a value model of the node itself constructed by comprehensively considering the relationship between the target and the war, the importance of the target in the system, and the threat of the target. The second is a node network value model based on the potential field theory. The third is to construct a cascading failure model of the target system through the definition of triples (results of strike action, target unit status, and failure influence relationship between target units). Fourth, with the optimal cost-effectiveness ratio as the objective function, the evaluation criterion function model is established. Case scenarios and simulation experiments illustrate the rationality and effectiveness of the method which can provide effective solutions for commanders to select key targets.

Th1-Dominant CD4+ T Cells Orchestrate Endogenous Systematic Antitumor Immune Memory After Cryo-Thermal Therapy.

Recent studies suggest that highly activated, polyfunctional CD4+ T cells are incredibly effective in strengthening and sustaining overall host antitumor immunity, promoting tumor-specific CD4+ T-cell responses and effectively enhancing antitumor immunity by immunotherapy. Previously, we developed a novel cryo-thermal therapy for local tumor ablation and achieved long-term survival rates in several tumor models. It was discovered that cryo-thermal therapy remodeled the tumor microenvironment and induced an antigen-specific CD4+ T-cell response, which mediated stronger antitumor immunity in vivo. In this study, the phenotype of bulk T cells in spleen was analyzed by flow cytometry after cryo-thermal therapy and both CD4+ Th1 and CD8+ CTL were activated. In addition, by using T-cell depletion, isolation, and adoptive T-cell therapy, it was found that cryo-thermal therapy induced Th1-dominant CD4+ T cells that directly inhibited the growth of tumor cells, promoted the maturation of MDSCs via CD4+ T-cell-derived IFN-γ and enhanced the cytotoxic effector function of NK cells and CD8+ T cells, and promoted the maturation of APCs via cell-cell contact and CD4+ T-cell-derived IFN-γ. Considering the multiple roles of cryo-thermal-induced Th1-dominant CD4+ T cells in augmenting antitumor immune memory, we suggest that local cryo-thermal therapy is an attractive thermo-immunotherapy strategy to harness host antitumor immunity and has great potential for clinical application.