Weak-formulated physics-informed modeling and optimization for heterogeneous digital materials.

Numerical solutions to partial differential equations (PDEs) are instrumental for material structural design where extensive data screening is needed. However, traditional numerical methods demand significant computational resources, highlighting the need for innovative optimization algorithms to streamline design exploration. Direct gradient-based optimization algorithms, while effective, rely on design initialization and require complex, problem-specific sensitivity derivations. The advent of machine learning offers a promising alternative to handling large parameter spaces. To further mitigate data dependency, researchers have developed physics-informed neural networks (PINNs) to learn directly from PDEs. However, the intrinsic continuity requirement of PINNs restricts their application in structural mechanics problems, especially for composite materials. Our work addresses this discontinuity issue by substituting the PDE residual with a weak formulation in the physics-informed training process. The proposed approach is exemplified in modeling digital materials, which are mathematical representations of complex composites that possess extreme structural discontinuity. This article also introduces an interactive process that integrates physics-informed loss with design objectives, eliminating the need for pretrained surrogate models or analytical sensitivity derivations. The results demonstrate that our approach can preserve the physical accuracy in data-free material surrogate modeling but also accelerates the direct optimization process without model pretraining.

The effect of ginsenoside Rg3 combined with chemotherapy on immune function in non-small cell lung cancer: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The occurrence and development of non-small cell lung cancer (NSCLC) are closely related to the immune status of the tumor-host. The immunosuppression caused by tumor cells and toxic side effects produced by chemotherapeutic drugs results in a decrease in immune function, ultimately leading to the failure of clinical chemotherapy treatment. Ginsenoside Rg3 has been clinically reported to have positive effects in enhancing immune function in patients. Thus, we screened and evaluated the quality of the evidence regarding the benefits of ginsenoside Rg3 and conducted a meta-analysis to assess the impact on improving immune function in NSCLC. METHODS: The PubMed, EMBASE, Cochrane Library, CNKI, Weipu (VIP), and Wanfang databases were searched in this study, all from the time of library construction to January 2023. RESULTS: In total,12 trials with a sample size of 1008 cases were included based on the eligible criteria. The results showed that compared with first-line chemotherapy alone, the combination of ginsenoside Rg3 and first-line chemotherapy could better improve level of the CD3+ T lymphocytes [mean difference (MD) = 4.72; 95% confidence intervals (CI): 3.92, 5.53; P < .00001], CD4+ T lymphocytes (MD = 4.93; 95% CI: 4.61, 5.26; P < .00001), CD8+ T lymphocytes (MD = 2.67; 95% CI: 0.93, 4.37; P = .003), CD4+/CD8+ T lymphocytes (MD = 0.20; 95% CI: 0.09, 0.32; P = .0006), increase the activity of nature killer cells (MD = 2.11; 95% CI: 0.58, 3.63; P = .007), recover the decline of the white blood cell count induced by chemotherapy, and improve the clinical efficacy for patients. CONCLUSION: This study confirmed that ginsenoside Rg3 has some efficacy advantages for improving immune function in patients with NSCLC.

Mucus-Penetrating Alginate-Chitosan Nanoparticles Loaded with Berberine Hydrochloride for Oral Delivery to the Inflammation Site of Ulcerative Colitis.

The rectal enemas of berberine hydrochloride (BH) have emerged as one of the most effective strategies in the clinical treatment of ulcerative colitis (UC). However, oral dosages of BH exhibit a poor anti-inflammatory effect of UC, which may attribute to premature absorption of BH by the upper gastrointestinal tract. Moreover, the thick colonic mucus layer obstructs the penetration of the drug, resulting in low bioavailability to the inflammatory site of the colon. The aim of this study was to develop the mucus-penetrating sodium alginate-chitosan nanoparticles (SA-CS NPs) for oral delivery of BH to the site of colonic ulcer lesions. BH-loaded SA-CS NPs were developed through the ionic gelation method and analyzed for physicochemical characteristics, release performance, penetrability, site retention, and therapeutic efficacy. The results showed that the NPs have a particle size of 257 nm with a negative charge, presenting desired pH-dependent release behavior. The permeation studies elucidated that negatively charged SA-CS NPs had 2.9 times higher mucus penetration ability than positively charged CS NPs. An ex vivo retention study indicated the high retention of BH-SA-CS NPs at the colon site for more than 16 h. In vivo therapeutic effectiveness demonstrated that the prepared NPs could not only alleviate colonic injury by decreasing the disease activity index and colon mucosa damage index, but also improve the immunologic function by decreasing the spleen index. In conclusion, the BH-SA-CS NPs could enhance the mucus permeability and deliver drugs to the colonic inflammation site, providing new insights into improving the therapeutic effect of UC.

Distinguishing iron deficiency anemia from thalassemia by the red blood cell lifespan with a simple CO breath test: a pilot study.

BACKGROUND: Extant indices for distinguishing between iron deficiency anemia (IDA) and thalassemia (Thal) have substantial practical limitations. The aim of this pilot study was to assess the predictive value of red blood cell lifespan (RBCLS), as determined by an automated CO breath test analysis approach, in the differential diagnosis of these two common forms of microcytic hypochromic anemia (MHA). METHODS: RBCLS measurements were conducted in 35 healthy controls (HCs) and 114 patients diagnosed with MHA (IDA, N = 59; and Thal, N = 55) with ELS TESTER that provides a direct RBCLS value read-out. RBCLS between IDA and Thal was compared and evaluated by referring to normal cut-off from the instrument. RESULTS: Compared with that in HCs, RBCLS in IDA and Thal groups was shortened; and median RBCLS was shorter in the Thal group than that in IDA group (33 d versus 79 d, p < 0.001). The median RBCLS in IDA patients with chronic gastrointestinal (GI) bleeding was shorter than that those without GI bleeding (38 d versus 100 d, p < 0.001). Using 75 d as a cut-off, RBCLS had a sensitivity of 96.4% and a specificity of 50.8% for detecting Thal. When GI bleeding patients were excluded from the IDA group, discriminant efficiency of RBCLS was further improved. CONCLUSIONS: MHA with a normal RBCLS is suggestive of IDA, whereas MHA with a significantly shortened RBCLS without signs of chronic GI bleeding is suggestive of Thal.

[Effects of Synthetic Long-Chain Polyphosphate on Blood Coagulation and Platelet Aggregation].

OBJECTIVE: To investigate the effects of synthetic long-chain polyphosphate on blood coagulation and platelet aggregation. METHODS: The effect of artificial synthetic long chain poly phosphate on blood coagulation and platelet aggregation was detected by coagulation tests, coagulation factor activity detection and platelet aggregation test, and its mechanism was explored by ELISA, flow cytometry and high content imaging system. RESULTS: The long chain polyphosphates prolonged activated partial thromboplastin time, decreased coagulation factor FⅧ, FⅨ, FⅪ and FⅫ activity, blocked ADP-induced platelet aggregation, and decreased the concentration of calcium and TXA2 in platelet. CONCLUSION: The synthetic long-chain polyphosphate can inhibit endogenous coagulation and inhibit platelet aggregation, which may be related with the inhibition of intracellular calcium and TXA2.