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A novel method is introduced in this work for effectively evaluating the performance of the PANDA type polarization-maintaining fiber Bragg grating (PANDA-FBG) distributed dynamic strain and temperature sensing system. Conventionally, the errors during the measurement are unknown or evaluated by using other sensors such as strain gauge and thermocouples. This will make the sensing system complicated and decrease the efficiency since more than one kind of sensor is applied for the same measurand. In this study, we used the approximately constant ratio of primary errors in strain and temperature measurement and realized the self-evaluation of the sensing system, which can significantly enhance the applicability, as well as the reliability in strategy making.

Immunogenic cell death (ICD)-associated immunogenicity can be evoked through reactive oxygen species (ROS) produced via endoplasmic reticulum (ER) stress. In this study, we generate a double ER-targeting strategy to realize photodynamic therapy (PDT) photothermal therapy (PTT) immunotherapy. This nanosystem consists of ER-targeting pardaxin (FAL) peptides modified-, indocyanine green (ICG) conjugated- hollow gold nanospheres (FAL-ICG-HAuNS), together with an oxygen-delivering hemoglobin (Hb) liposome (FAL-Hb lipo), designed to reverse hypoxia. Compared with non-targeting nanosystems, the ER-targeting naosystem induces robust ER stress and calreticulin (CRT) exposure on the cell surface under near-infrared (NIR) light irradiation. CRT, a marker for ICD, acts as an ‘eat me’ signal to stimulate the antigen presenting function of dendritic cells. As a result, a series of immunological responses are activated, including CD8 + T cell proliferation and cytotoxic cytokine secretion. In conclusion, ER-targeting PDT-PTT promoted ICD-associated immunotherapy through direct ROS-based ER stress and exhibited enhanced anti-tumour efficacy. Reactive oxygen species induced by endoplasmic reitculum stress can be exploited for cancer therapy. Here, nanoparticles are targetted to the endoplasmic reticulum and, when accompanied by PDT, produce stress resulting in calreticulin exposure on the cell surface, which activates dendritic cells.

Some research has suggested that miRNA-10a (miR-10a-5p) had an inhibitory function in proliferation and invasion of cancers. Whereas the role of miR-10a-5p in melanoma has not been fully explored. This study aims to confirm LIN28B as the targeted gene of miR-10a-5p which was explored in melanoma cells. In addition, upstream regulatory molecule of miR-10a-5p was also investigated in melanoma cells. Real-time Quantitative polymerase chain reaction (RT-qPCR) was adopted to analyze miR-10a-5p expression level in melanoma and the normal human epidermal melanocyte cells. Several biological assays were performed to evaluate miR-10a-5p influences on cell proliferation, migration and invasion ability in A375 and B16-F10 cells. Gene prediction of miRNA targeting and a dual luciferase assay were applied to assess miR-10a-5p-targeted LIN28B. Western blot assessed the impacts of miR-10a-5p on the protein expression of LIN28B. Western blot analyzed the TCF21 effects on the expression of LIN28B and RT-qPCR assessed the influence of TCF21 on the expression level of miRNA-10a. In addition, Chromatin Immunoprecipitation (ChIP) Assay and JASPAR databases were employed to explore the regulatory relationship between TCF21 and miR-10a-5p. We discovered that miR-10a-5p expression was lower in melanoma cells and high expression of miR-10a-5p suppressed the proliferation, migration and invasion abilities of melanoma cells. We also discovered that miR-10a-5p targeted the LIN28B mRNA 3'UTR area and diminished LIN28B protein expression. We found that LIN28B expression was strongly decreased by TCF21 upregulation in the two melanoma cells. The qRT-PCR assay showed that miR-10a-5p expression level was obviously boosted by increased TCF21 expression. The results also demonstrated that TCF21 directly regulated miR-10a-5p at transcript levels. TCF21 induced miRNA-10a targeting LIN28B could affect the progression and growth of melanoma.

Despite advancements in antiretroviral therapy (ART) suppressing HIV-1 replication, existing antiviral drugs pose limitations, including lifelong medication, frequent administration, side effects and viral resistance, necessitating novel HIV-1 treatment approaches. CD4, pivotal for HIV-1 entry, poses challenges for drug development due to neutralization and cytotoxicity concerns. Nevertheless, Ibalizumab, the sole approved CD4-specific antibody for HIV-1 treatment, reignites interest in exploring alternative anti-HIV targets, emphasizing CD4’s potential value for effective drug development. Here, we explore anti-CD4 nanobodies, particularly Nb457 from a CD4-immunized alpaca. Nb457 displays high potency and broad-spectrum activity against HIV-1, surpassing Ibalizumab’s efficacy. Strikingly, engineered trimeric Nb457 nanobodies achieve complete inhibition against live HIV-1, outperforming Ibalizumab and parental Nb457. Structural analysis unveils Nb457-induced CD4 conformational changes impeding viral entry. Notably, Nb457 demonstrates therapeutic efficacy in humanized female mouse models. Our findings highlight anti-CD4 nanobodies as promising HIV-1 therapeutics, with potential implications for advancing clinical treatment against this global health challenge. In this study, Zhu et al. report Nb457, an alpaca-derived nanobody with broad-spectrum anti-HIV1 activity and show that Nb457 induces conformational changes in CD4, blocking viral entry and completely inhibiting HIV-1 in its trimeric form.

Pyrano[2,3-c]pyrazole derivatives have been reported as exerting various biological activities. One compound with potential anti-tumor activity was screened out by MTT assay from series of dihydropyrazopyrazole derivatives we had synthesized before using a one-pot, four-component reaction, and was named as 6-amino-4-(2-hydroxyphenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (hereinafter abbreviated as AMDPC). The IC50 of AMDPC against Bcap-37 breast cancer cells was 46.52 μg/mL. Then the hydrophobic AMDPC was encapsulated in PEG-PLGA block copolymers, and then self-assembled as polymeric micelle (mPEG-PLGA/AMDPC) to improve both physiochemical and release profiles. The effect of mPEG-PLGA/AMDPC on BCAP-37 cancer cells showed similar anti-tumor effects as AMDPC. Furthermore, the anti-tumor mechanism of mPEG-PLGA/AMDPC was investigated, which can probably be attributed to stimulating the expression of P21 gene and therefore protein production on BCAP-37 cells, and then blocked the cell cycle through the P53-independent pathway both in S phase and G2 phase. Thus, mPEG-PLGA/AMDPC is a promising therapeutic agent for cancer treatment, and further in vivo studies will be developed.

The light-driven enzyme catalytic system composed of NAD(P)H regeneration and NAD(P)H-dependent enzymatic process emerges as a biomanufacturing platform for the synthesis of value-added chemicals, where the photo-responsive materials absorb solar energy to drive mass conversion. Herein, we report a photo-enzyme-membrane (PEM) catalytic system coupled with multi-enzyme cascade for ethylene glycol (EG) synthesis, in which membrane mediates energy transfer and mass conversion. Covalent organic polymer membrane as photo-membrane (PM) affords efficient NADH supply through synergistic intensification of electron transfer and proton transfer, where the bipyridine moiety mediates fast electron transfer from the generation site, and the sulfonic acid moiety facilitates proton transfer by enriching protons. Meanwhile, NADH-dependent enzyme is absorbed on PM followed by coating with a silica layer to form PEM, where the enzyme-bearing silica layer is defined as enzyme-membrane (EM). The enzymatic process is intensified by mitigating the adverse effects of PM on enzyme activity through precise regulation of EM thickness. Further, a dual-channel reactor is constructed for sustainable synthesis of EG with an initial synthesis rate of 2.43 mmol g PEM -1 h -1 by continuous supply of methanol. Our study offers an efficient and durable light-driven enzyme catalytic system for the synthesis of C 2+ from C 1 chemicals. The light-driven enzyme catalytic systems composed of NAD(P)H regeneration and NAD(P)H-dependent enzymatic process emerge as biomanufacturing platforms for the synthesis of value-added chemicals. Here, the authors present a photo-enzyme-membrane catalytic system coupled with multi-enzyme cascade for ethylene glycol synthesis.

Objectives To evaluate the potential diagnostic value of MR elastography (MRE)–based stiffness to noninvasively predict the microvascular invasion (MVI) grade in hepatocellular carcinoma (HCC). Methods One hundred eighty-five patients with histopathology-proven HCC who underwent MRI and MRE examinations before hepatectomy were retrospectively enrolled. According to the three-tiered MVI grading system, the MVI was divided into negative-MVI ( n = 89) and positive-MVI ( n = 96) groups, and the latter group was categorized into mild-MVI ( n = 49) and severe-MVI ( n = 47) subgroups. Logistic regression and area under the receiver operating characteristic curve (AUC) analyses were used to determine the predictors associated with MVI grade and analyze their performances, respectively. Results Among the 185 patients, tumor size ≥ 50 mm ( p = 0.031), tumor stiffness (TS)/liver stiffness (LS) > 1.47 ( p = 0.001), TS > 4.33 kPa ( p < 0.001), and nonsmooth tumor margin ( p = 0.006) were significant independent predictors for positive-MVI. Further analyzing the subgroups, tumor size ≥ 50 mm ( p < 0.001), TS > 5.35 kPa ( p = 0.001), and AFP level > 400 ng/mL ( p = 0.044) were independently associated with severe-MVI. The models incorporating MRE and clinical-radiological features together performed better for evaluating positive-MVI (AUC: 0.846) and severe-MVI (AUC: 0.802) than the models using clinical-radiological predictors alone (AUC: positive-/severe-MVI, 0.737/0.743). Analysis of recurrence-free survival and overall survival showed the predicted positive-MVI/severe-MVI groups based on combined models had significantly poorer prognoses than predicted negative-MVI/mild-MVI groups, respectively (all p < 0.05). Conclusions MRE-based stiffness was an independent predictor for both the positive-MVI and severe-MVI. The combination of MRE and clinical-radiological models might be a useful tool for evaluating HCC patients’ prognoses underwent hepatectomy by preoperatively predicting the MVI grade. Key Points • The severe-microvascular invasion (MVI) grade had the highest tumor stiffness (TS), followed by mild-MVI and non-MVI, and there were significances among the three different MVI grades . • MR elastography (MRE)–based stiffness value was an independent predictor of positive-MVI and severe-MVI in hepatocellular carcinoma (HCC) preoperatively . • When combined with clinical-radiological models, MRE could significantly improve the predictive performance for MVI grade. Patients with predicted positive-MVI/severe-MVI based on the combined models had worse recurrence-free survival and overall survival than those with negative-MVI/mild-MVI, respectively .

Most animal species display dimorphic sexual behaviors and male-biased aggressiveness. Current models have focused on the male-specific product from the fruitless (fruM ) gene, which controls male courtship and male-specific aggression patterns in fruit flies, and describe a male-specific mechanism underlying sexually dimorphic behaviors. Here we show that the doublesex (dsx) gene, which expresses male-specific DsxM and femalespecific DsxF transcription factors, functions in the nervous system to control both male and female sexual and aggressive behaviors. We find that Dsx is not only required in central brain neurons for male and female sexual behaviors, but also functions in approximately eight pairs of male-specific neurons to promote male aggressiveness and approximately two pairs of female-specific neurons to inhibit female aggressiveness. DsxF knockdown females fight more frequently, even with males. Our findings reveal crucial roles of dsx, which is broadly conserved from worms to humans, in a small number of neurons in both sexes to establish dimorphic sexual and aggressive behaviors.

Low sintering temperature and good temperature stability are the crucial parameters for the actual application of the dielectric capacitors. In this work, lead-free relaxor ferroelectric ceramics with chemical formula (1 −  x )(Ba 0.4 Sr 0.6 )TiO 3 - x Bi(Zn 2/3 Nb 1/3 )O 3 [(1 −  x )BST- x BZN, ( x  = 0.00 to 0.225)] were developed through a solid-state synthesis route. The microstructures, dielectric performance, and temperature stability were studied in detail. The results show that 0.775BST-0.225BZN bulk ceramic with capacitance-temperature dependence satisfied with X8R specification can be obtained at a sintering temperature of 1140 °C. In addition, the energy storage performance of 0.775BST-0.225BZN bulk ceramic exhibits good temperature stability in a wide range of temperatures from 25 to 150 °C. High dispersion results in capacitance-temperature stability and energy storage stability. More importantly, the 0.775BST-0.225BZN ceramic also displays good charge–discharge performance dependence on temperatures (variations of the current density and power density are less than 3% over 25–150 °C). These results demonstrate that 0.775BST-0.225BZN lead-free ceramic is a potential material for dielectric capacitors that can be operated in a wide range of temperatures.

The combination of DNA damage response inhibitors (DDR inhibitors) has emerged as a promising strategy for anticancer therapy. Herein, we demonstrate that the combined administration of poly (ADP-ribose) polymerase (PARP) and ataxia telangiectasia and Rad3-related (ATR) inhibitors elicits PANoptosis across diverse cellular lineages, including non-cancerous cell populations. The induction of PANoptosis is dependent on mitotic entry and ZBP1-dependent PANoptosome (ZBP1-RIPK1-Caspase8-Caspase6). We identify the Aurora kinase B (AURKB) as the upstream regulator, essential for phosphorylation of ZBP1 which impacts ZBP1-dependent PANoptosome assembly and activation. The Trp53 -/- Brca1 -/- model of ID8 and two patient-derived xenograft (PDX) models further confirm the occurrence of PANoptosis following combination administration in vivo. The toxicity is mitigated in ZBP1-knockout mice. This study unveils a mechanism that dictates cell fate during DDR inhibitors-induced aberrant mitosis, emphasizing the critical balance between efficacy and safety in optimizing DDR inhibitors combination therapies. DNA damage response inhibitors are a promising cancer therapy. Here, the authors show that combined PARP and ATR inhibition triggers ZBP1-dependent PANoptosis in cancer and normal cells, revealing a mechanism to balance efficacy and toxicity in DDR inhibitor therapies.