Mitochondria-Regulated Information Processing Nanosystem Promoting Immune Cell Communication for Liver Fibrosis Regression.

Liver fibrosis is a coordinated response to tissue injury that is mediated by immune cell interactions. A mitochondria-regulated information-processing (MIP) nanosystem that promotes immune cell communication and interactions to inhibit liver fibrosis is designed. The MIP nanosystem mimics the alkaline amino acid domain of mitochondrial precursor proteins, providing precise targeting of the mitochondria. The MIP nanosystem is driven by light to modulate the mitochondria of hepatic stellate cells, resulting in the release of mitochondrial DNA into the fibrotic microenvironment, as detected by macrophages. By activating the STING signaling pathway, the developed nanosystem-induced macrophage phenotype switches to a reparative subtype (Ly6Clow) and downstream immunostimulatory transcriptional activity, fully restoring the fibrotic liver to its normal tissue state. The MIP nanosystem serves as an advanced information transfer system, allowing precise regulation of trained immunity, and offers a promising approach for effective liver fibrosis immunotherapy with the potential for clinical translation.

Design and Fabrication of Biomass Derived Black Carbon Modified g-C3N4/FeIn2S4 Heterojunction as Highly Efficient Photocatalyst for Wastewater Treatment.

The environmental deterioration caused by dye wastewater discharge has received considerable attention in recent decades. One of the most promising approaches to addressing the aforementioned environmental issue is the development of photocatalysts with high solar energy consumption efficiency for the treatment of dye-contaminated water. In this study, a novel low-cost π-π biomass-derived black carbon modified g-C3N4 coupled FeIn2S4 composite (i.e., FeInS/BC-CN) photocatalyst is successfully designed and fabricated that reveals significantly improved photocatalytic performance for the degradation of Eosin Yellow (EY) dye in aqueous solution. Under dark and subsequent visible light irradiation, the amount optimized composite reveals 99% removal performance for EY dye, almost three-fold compared to that of the pristine FeInS and BC-CN counterparts. Further, it is confirmed by means of the electron spin resonance spectrometry, quenching experiments, and density functional theory (DFT) calculations, that the hydroxyl radicals (•OH) and superoxide radicals (•O2 -) are the dominant oxidation species involved in the degradation process of EY dye. In addition, a systematic photocatalytic degradation route is proposed based on the resultant degradation intermediates detectedduring liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. This work provides an innovative idea for the development of advanced photocatalysts to mitigate water pollution.

Differences in Vertebral Morphology and bone Mineral Density between Grade 1 Vertebral Fracture and Non-Fractured Participants in the Chinese Population.

PURPOSE: To investigate the difference in vertebral morphology and bone mineral density (BMD) between grade 1 VFs and non-fractured participants in the Chinese population to shed light on the clinical significance of grade 1 VFs from various perspectives. METHODS: This retrospective cohort study included patients who received a chest low-dose computed tomography (LDCT) scan for health examination and visited the First Affiliated Hospital of Zhengzhou University, Henan, China, from October 2019 to August 2022. Data were analyzed from March 2023 to July 2023. The main outcome of this study was the difference in morphological parameters and BMD between grade 1 VFs and non-fractured participants. The prevalence of grade 1 VFs in China populations was calculated. The difference in BMD of three fracture types in the Grade 1 group was also evaluated. RESULTS: A total of 3652 participants (1799 males, 54.85 ± 9.02 years, range, 40-92 years; 1853 females, 56.00 ± 9.08 years, range, 40-93 years) were included. The prevalence of grade 2 and 3 increase with age. The prevalence of grade 1 VFs gradually increases ≤ 50y to 60-69y group, but there is a decrease in the ≥ 70 years male group (6.6%) and a rise in the female group (25.5%). There was no significant statistical difference observed in vertebral shape indices (VSI) and BMD between the Grade 1 group and the no-fractured group aged < 50 years old except the wedge index in male. The biconcavity index did not differ between the non-fractured group and the Grade 1 group in men aged 50-59 years, whereas a significant statistical difference was observed in women. Additionally, the results of BMD were consistent with these findings. For the 40-59 years age group, there were significant differences between the compression deformity group and the other groups. CONCLUSIONS: The grade 1 group had higher VSI and lower BMD than the non-fractured group, suggesting an association between the Grade 1 group and osteoporosis in individuals aged over 50 for women and over 60 for men. Different fracture types have significant variations in BMD among middle-aged people. The prevalence of grade 1 VFs exhibits an age-related increase in both genders, with opposite trends observed between older males and females. We suggested VSI can aid physicians in the diagnosis of grade 1 VFs.

3D U-Net Neural Network Architecture-Assisted LDCT to Acquire Vertebral Morphology Parameters: A Vertebral Morphology Comprehensive Analysis in a Chinese Population.

To evaluate the feasibility of acquiring vertebral height from chest low-dose computed tomography (LDCT) images using an artificial intelligence (AI) system based on 3D U-Net vertebral segmentation technology and the correlation and features of vertebral morphology with sex and age of the Chinese population. Patients who underwent chest LDCT between September 2020 and April 2023 were enrolled. The Altman and Pearson's correlation analyses were used to compare the correlation and consistency between the AI software and manual measurement of vertebral height. The anterior height (Ha), middle height (Hm), posterior height (Hp), and vertebral height ratios (VHRs) (Ha/Hp and Hm/Hp) were measured from T1 to L2 using an AI system. The VHR is the ratio of Ha to Hp or the ratio of Hm to Hp of the vertebrae, which can reflect the shape of the anterior wedge and biconcave vertebrae. Changes in these parameters, particularly the VHR, were analysed at different vertebral levels in different age and sex groups. The results of the AI methods were highly consistent and correlated with manual measurements. The Pearson's correlation coefficients were 0.855, 0.919, and 0.846, respectively. The trend of VHRs showed troughs at T7 and T11 and a peak at T9; however, Hm/Hp showed slight fluctuations. Regarding the VHR, significant sex differences were found at L1 and L2 in all age bands. This innovative study focuses on vertebral morphology for opportunistic analysis in the mainland Chinese population and the distribution tendency of vertebral morphology with ageing using a chest LDCT aided by an AI system based on 3D U-Net vertebral segmentation technology. The AI system demonstrates the potential to automatically perform opportunistic vertebral morphology analyses using LDCT scans obtained during lung cancer screening. We advocate the use of age-, sex-, and vertebral level-specific criteria for the morphometric evaluation of vertebral osteoporotic fractures for a more accurate diagnosis of vertebral fractures and spinal pathologies.

STC-UNet: renal tumor segmentation based on enhanced feature extraction at different network levels.

Renal tumors are one of the common diseases of urology, and precise segmentation of these tumors plays a crucial role in aiding physicians to improve diagnostic accuracy and treatment effectiveness. Nevertheless, inherent challenges associated with renal tumors, such as indistinct boundaries, morphological variations, and uncertainties in size and location, segmenting renal tumors accurately remains a significant challenge in the field of medical image segmentation. With the development of deep learning, substantial achievements have been made in the domain of medical image segmentation. However, existing models lack specificity in extracting features of renal tumors across different network hierarchies, which results in insufficient extraction of renal tumor features and subsequently affects the accuracy of renal tumor segmentation. To address this issue, we propose the Selective Kernel, Vision Transformer, and Coordinate Attention Enhanced U-Net (STC-UNet). This model aims to enhance feature extraction, adapting to the distinctive characteristics of renal tumors across various network levels. Specifically, the Selective Kernel modules are introduced in the shallow layers of the U-Net, where detailed features are more abundant. By selectively employing convolutional kernels of different scales, the model enhances its capability to extract detailed features of renal tumors across multiple scales. Subsequently, in the deeper layers of the network, where feature maps are smaller yet contain rich semantic information, the Vision Transformer modules are integrated in a non-patch manner. These assist the model in capturing long-range contextual information globally. Their non-patch implementation facilitates the capture of fine-grained features, thereby achieving collaborative enhancement of global-local information and ultimately strengthening the model's extraction of semantic features of renal tumors. Finally, in the decoder segment, the Coordinate Attention modules embedding positional information are proposed aiming to enhance the model's feature recovery and tumor region localization capabilities. Our model is validated on the KiTS19 dataset, and experimental results indicate that compared to the baseline model, STC-UNet shows improvements of 1.60%, 2.02%, 2.27%, 1.18%, 1.52%, and 1.35% in IoU, Dice, Accuracy, Precision, Recall, and F1-score, respectively. Furthermore, the experimental results demonstrate that the proposed STC-UNet method surpasses other advanced algorithms in both visual effectiveness and objective evaluation metrics.

Curcumin alleviates zearalenone-induced liver injury in mice by scavenging reactive oxygen species and inhibiting mitochondrial apoptosis pathway.

Curcumin (CUR) is a compound extracted from turmeric that has a variety of functions including antioxidant and anti-inflammatory. As an estrogen-like mycotoxin, zearalenone (ZEN) not only attacks the reproductive system, but also has toxic effects on the liver. However, whether CUR can alleviate ZEN-induced liver injury remains unclear. This paper aims to investigate the protective effect of CUR against ZEN-induced liver injury in mice and explore the molecular mechanism involved. BALB/c mice were randomly divided into control (CON) group, CUR group (200 mg/kg b. w. CUR), ZEN group (40 mg/kg b. w. ZEN) and CUR+ZEN group (200 mg/kg b. w. CUR+40 mg/kg b. w. ZEN). 28 d after ZEN exposure and CUR treatment, blood and liver samples were collected for subsequent testing. The results showed that CUR reversed ZEN-induced hepatocyte swelling and necrosis in mice. It significantly reduced the serum alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in mice (p < 0.05). In addition, CUR significantly reduced hepatic ROS, malondialdehyde, hydrogen peroxide and apoptosis levels in mice (p < 0.05). Quantitative RT-PCR and Western blot results showed that CUR significantly reduced the expression of Bax and Caspase3, and reversed the increase of Nrf2, HO-1 and NQO1 expression in the liver of mice induced by ZEN (p < 0.05). In conclusion, CUR alleviated ZEN-induced liver injury in mice by scavenging ROS and inhibiting the mitochondrial apoptotic pathway.

Effects of Separation and Purification Methods on Antioxidation, Hypoglycemic and DNA Protection Activity of Fenugreek Polysaccharide.

Six low molecular weight fenugreek polysaccharides (FP) were isolated and purified by ethanol stepwise precipitation (EFP-20, EFP-40, and EFP-60) and DEAE-52 cellulose column method (DFP-0, DFP-0.15, and DFP-0.3), respectively. The effects of different separation and purification techniques on the preliminary properties and biological activities of fenugreek polysaccharides were compared. The results showed that the DEAE-52 cellulose-eluted fractions had a higher total sugar content and displayed a looser structure. The molecular weights of all six fractions were in the range of 4-19 kDa, with significant changes in the ratio of galactose to mannose. All six fractions contained α-D-galactopyranose and ß-D-mannopyranose structures. Activity tests showed that all six fractions possessed antioxidant, hypoglycemic and DNA-protective activities. Among them, the DFP-0 fraction showed the highest activity. Overall, different isolation and purification methods lead to changes in the properties and bioactivities of FP, which provides a theoretical basis for the development and application of FP in functional foods and drugs.

Synthesis, Thermal Stability and Antifungal Evaluation of Two New Pyrrole Esters.

To develop new chemicals that are stable at high temperatures with biological activity, a pyrrole intermediate was firstly synthesized using glucosamine hydrochloride as raw materials through cyclization and oxidation. Further, two novel pyrrole ester derivatives were prepared via Steglich esterification from pyrrole intermediate with vanillin and ethyl maltol, respectively. Nuclear magnetic resonance (1 H-NMR, 13 C NMR), infrared spectroscopy (IR) and high resolution mass spectrometry (HRMS) were used to confirm the target compounds. Thermal behavior of the compounds was investigated by thermogravimetry (TG), differential scanning calorimeter (DSC) and the pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) methods. The plausible pyrolytic mechanism was proposed. Additionally, their biological activities against the pathogens Fusarium graminearum, Fusarium oxysporum, Fusarium moniliforme, Phytophthora nicotianae, and Rhizoctonia solani were assessed. These target compounds showed outstanding antifungal activities and the highest inhibitor rates of 62.50 % and 68.75 % against R. solani with EC50 values of 0.0296 and 0.0200 mg mL-1 , respectively. SDHI protein sequence was molecularly docked to identify the binding mechanisms in the active pocket and examine the interactions between both the molecules and the SDHI protein.

Strengthening Mechanism of Polyurea to Anti-Penetration Performance of Spherical Cell Porous Aluminum.

A composite structure containing a metallic skeleton and polyurea elastomer interpenetrating phase was fabricated, and its anti-penetration performance for low-velocity large mass fragments was experimentally studied. The protection capacity of three polyurea was compared based on the penetration resistance force measurement. Results show that the polyurea coating layer at the backside improves the performance of the polyurea-filled spherical cell porous aluminum (SCPA) plate due to its backside support effect and phase transition effect, which are accompanied by a large amount of energy absorption. The frontal-side-coated polyurea layer failed to shear and provided a very limited strengthening effect on the penetration resistance of the interpenetrating phase composite panel. The filling polyurea in SCPA increased the damage area and formed a compression cone for the backside coating layer, leading to a significant stress diffusion effect. The anti-penetration performance was synergistically improved by the plug block effect of the interpenetrating phase composite and the backside support effect of the PU coating layer. Compared with SCPA, the initial impact failure strength and the average resistance force of the composite plate were improved by 120-200% and 108-274%, respectively.

Diet xylo-oligosaccharide supplementation improves growth performance, immune function, and intestinal health of broilers.

The effects of xylo-oligosaccharides (XOS) on broiler growth performance, immune function, and intestinal health were investigated. A total of 540 one-d-old Arbor Acres Plus broilers were randomly divided into 5 groups with 6 replicates per group and 18 chickens per replicate. Broilers in the control (CON) group received a corn-soybean meal based basal diet, those in the antibiotics (ANT) group received the basal diet plus 500 mg/kg oxytetracycline, and those in XOS groups received the basal diet plus 150, 300, or 450 mg/kg XOS. Compared with CON, the body weight at 42 d and average daily gain from 1 to 42 d were significantly increased in the 150, 450 mg/kg XOS-added and ANT groups (P = 0.018), and the relative expression of claudin-1 and ZO-1 mRNA in the ileum was significantly higher in the 300 and 450 mg/kg XOS-added groups (P < 0.001). The feed conversion ratios (P < 0.001) and abdominal fat rates (P = 0.012) of broilers from 1 to 42 d of age were significantly lower in all XOS-added groups than in the control group. Splenic index (P = 0.036) and bursa of Fabricius index (P = 0.009) were significantly better in the ANT group and each XOS-added group than in the control group. Compared to CON and ANT, serum IgA (P = 0.007) and IgG (P = 0.002) levels were significantly higher in the 300 mg/kg XOS-added group, and the relative abundance of short-chain fatty acid-producing genera (Alistipes) was also significantly higher (P < 0.001). Meanwhile, ileal villus height (P < 0.001) and ratio of villus height to crypt depth (V:C) (P = 0.001) were significantly increased in XOS-added broilers. In analysis of relationships between cecal microbes and the physical barrier of the gut, [Ruminococcus]_torques_group was positively correlated with mRNA expression of ileal ZO-1 and claudin-1 (P < 0.05), and Bacteroides was positively correlated with increased ileal villus height and V:C (P < 0.05). Overall, XOS addition to broiler diets improved growth performance, promoted intestinal health by enhancing intestinal barrier function and regulating cecal microbiota diversity, and had positive effects on immunity.

A temperature-compensated CO2 detection system based on non-dispersive infrared spectral technology.

The concentration of carbon dioxide (CO2) is an important indicator for coal mine safety. Real-time monitoring of CO2 concentration is of great importance for taking actions in advance to avoid the occurrence of potential accidents. To address the issues of poor portability and high cost associated with existing coal mine CO2 detection equipment, this paper develops a miniaturized CO2 detection system based on non-dispersive infrared (NDIR) technology. This sensor integrates an infrared light source and a dual-channel pyroelectric detector into a reflective gas chamber, thereby achieving an extended optical path and higher system sensitivity within limited space. Meanwhile, the noise interference was greatly mitigated by using hardware and software filtering techniques. Based on principle analysis, the Lambert-Beer law was parametrically corrected, and then, a model relationship between the dual-channel voltage ratio and concentration was established. In addition, temperature compensation for zero and span values was introduced to improve the adaptability of the detection results to temperature changes. Testing results indicate that the developed detection system can realize CO2 measurement in the concentration range of 0 to 50 000 ppm within a temperature range of 0-40 °C, with a maximum detection error of less than 0.12% and a repeatability deviation of less than 1.04%. During a stability test for 12 h, the maximum concentration drift is 0.07%, indicating that the developed system meets the requirements for monitoring CO2 safety in coal mines.

Mechanism of Salt Precipitation Blockage in Low-Producing Gas Wells and the Method of Acidification Blockage Removal.

In the Changqing area, over 23.6% of gas wells produce less than 0.1 × 104 m3/d of gas daily, posing a challenge to gas field sustainability. Laboratory analysis of scale samples from three wells and formation water analysis via inductively coupled plasma revealed soluble salt as the primary well blockage, with sodium chloride and calcium chloride comprising 48.0-81.2% of total content. The G3# well blockage contains a small amount of quartz from acid-insoluble components of carbonate acidification. Formation water from all wells exhibited high salinity (up to 153 g/L) with a calcium chloride water type. Scanning electron microscopy and EDS confirmed halite and quartz features in blockage samples. Theoretical calculations show salt crystallization when tubing pressure falls below 10 MPa and daily water production is <1.0 tons/day. Lower production leads to lower tubing pressure and higher salt precipitation at the bottom of the well. For G1# and G2# blockages, HCl dissolves >90%, and water >85%, making them suitable removal agents. For 3# blockage, mud acid with >80% dissolution is recommended. Chemical methods effectively clean the wellbore and formation. Optimized blockage removal measures increase tubing pressure and daily production by 2.18 and 4.05 times, respectively. This study offers insights into addressing well blockage challenges in low-producing gas wells.

A Living Microecological Hydrogel with Microbiota Remodeling and Immune Reinstatement for Diabetic Wound Healing.

Dysregulated skin microbiota and compromised immune responses are the major etiological factors for non-healing diabetic wounds. Current antibacterial strategies fail to orchestrate immune responses and indiscriminately eradicate bacteria at the wound site, exacerbating the imbalance of microbiota. Drawing inspiration from the beneficial impacts that probiotics possess on microbiota, a living microecological hydrogel containing Lactobacillus plantarum and fructooligosaccharide (LP/FOS@Gel) is formulated to remodel dysregulated skin microbiota and reinstate compromised immune responses, cultivating a conducive environment for optimal wound healing. LP/FOS@Gel acts as an "evocator," skillfully integrating the skin microecology, promoting the proliferation of Lactobacillus, Ralstonia, Muribaculum, Bacillus, and Allobaculum, while eradicating colonized pathogenic bacteria. Concurrently, LP/FOS@Gel continuously generates lactic acid to elicit a reparative macrophage response and impede the activation of the nuclear factor kappa-B pathway, effectively alleviating inflammation. As an intelligent microecological system, LP/FOS@Gel reinstates the skin's sovereignty during the healing process and effectively orchestrates the harmonious dialogue between the host immune system and microorganisms, thereby fostering the healing of diabetic infectious wounds. These remarkable attributes render LP/FOS@Gel highly advantageous for pragmatic clinical applications.

Role of the microbiota-gut-heart axis between bile acids and cardiovascular disease.

Bile acid (BA) receptors (e.g., farnesoid X-activated receptor, muscarinic receptor) are expressed in cardiomyocytes, endothelial cells, and vascular smooth muscle cells, indicating the relevance of BAs to cardiovascular disease (CVD). Hydrophobic BAs are cardiotoxic, while hydrophilic BAs are cardioprotective. For example, fetal cardiac insufficiency in maternal intrahepatic cholestasis during pregnancy, and the degree of fetal cardiac abnormality, is closely related to the level of hydrophobic BAs in maternal blood and infant blood. However, ursodeoxycholic acid (the most hydrophilic BA) can reverse/prevent these detrimental effects of increased levels of hydrophobic BAs on the heart. The gut microbiota (GM) and GM metabolites (especially secondary BAs) have crucial roles in hypertension, atherosclerosis, unstable angina, and heart failure. Herein, we describe the relationship between CVD and the GM at the BA level. We combine the concept of the "microbiota-gut-heart axis" (MGHA) and postulate the role and mechanism of BAs in CVD development. In addition, the strategies for treating CVD with BAs under the MGHA are proposed.

PDK4-mediated Nrf2 inactivation contributes to oxidative stress and diabetic kidney injury.

Diabetic kidney disease (DKD) is often featured with redox dyshomeostatis. Pyruvate dehydrogenase kinase 4 (PDK4) is the hub for DKD development. However, the mechanism by which PDK4 mediates DKD is poorly understood. The current work aimed to elucidate the relationship between PDK4 and DKD from the perspective of redox manipulation. Oxidative stress was observed in the human proximal tubular cell line (HK-2 cells) treated with a high concentration of glucose and palmitic acid (HGL). The mechanistic study showed that PDK4 could upregulate Kelch-like ECH-associated protein 1 (Keap1) in HGL-treated HK-2 cells through the suppression of autophagy, resulting in the depletion of nuclear factor erythroid 2-related factor 2 (Nrf2), the master regulator of redox homeostasis. At the cellular level, pharmacological inhibition or genetic knockdown of PDK4 could boost Nrf2, followed by the increase of a plethora of antioxidant enzymes and ferroptosis-suppression enzymes. Meanwhile, the inhibition or knockdown of PDK4 remodeled iron metabolism, further mitigating oxidative stress and lipid peroxidation. The same trend was observed in the DKD mice model. The current work highlighted the role of PDK4 in the development of DKD and suggested that PDK4 might be a promising target for the management of DKD.

Moisturizing and aroma-enhancing effects of low molecular weight fenugreek polysaccharides in cigarettes.

Polysaccharides possess excellent moisturizing effects due to their abundance of hydrophilic groups and film-forming properties. Additionally, they can produce a refreshing aroma during the pyrolysis process. However, there is scarce research on their application in the tobacco field. Herein, we investigated the effects of low molecular weight fenugreek polysaccharide (FP) obtained through ethanol fractionation and DEAE-52 cellulose column chromatography on moisture retention and aroma enhancement in tobacco. The moisture retention test revealed that the addition of FP increased the moisture retention index (MRI) of tobacco by 11.72 %-16.69 %, indicating that the hydrophilic nature of polysaccharides facilitated the migration of free water in tobacco to bound water, resulting in reduced water activity. Moreover, the contact angle between polysaccharide and tobacco was <90°, enabling better infiltration into tobacco and slowing down tobacco shrinkage caused by water loss. Among all the components, EFP-20 and EFP-40 demonstrated superior performance. Furthermore, FP exhibited excellent thermal stability below 200 °C and can decomposed to produce aromatic substances at high temperatures. It also demonstrated the ability to adsorb ethyl heptanoate and thermally decompose to produce a substantial amount of heptanoic acid. Consequently, the incorporation of FP in tobacco demonstrated favorable effects on both moisturization and aroma enhancement.

Dual-energy computed tomography and micro-computed tomography for assessing bone regeneration in a rabbit tibia model.

To gain a more meaningful understanding of bone regeneration, it is essential to select an appropriate assessment method. Micro-computed tomography (Micro-CT) is widely used for bone regeneration because it provides a substantially higher spatial resolution. Dual-energy computed tomography (DECT) ensure shorter scan time and lower radiation doses during quantitative evaluation. Therefore, in this study, DECT and Micro-CT were used to evaluate bone regeneration. We created 18 defects in the tibial plateau of the rabbits and filled them with porous polyetheretherketone implants to promote bone regeneration. At 4, 8, and 12 weeks, Micro-CT and DECT were used to assess the bone repair in the defect region. In comparison to Micro-CT (152 ± 54 mg/cm3), the calcium density values and hydroxyapatite density values obtained by DECT [DECT(Ca) and DECT(HAP)] consistently achieved lower values (59 ± 25 mg/cm3, 126 ± 53 mg/cm3). In addition, there was a good association between DECT and Micro-CT (R = 0.98; R2 = 0.96; DECT(Ca): y = 0.45x-8.31; DECT(HAP): y = 0.95x-17.60). This study highlights the need to use two different imaging methods, each with its advantages and disadvantages, to better understand the bone regeneration process.

Rational design of Near-Infrared fluorescent probe for monitoring HNO in plants.

Nitroxyl (HNO), a reactive nitrogen species (RNS), is essential for plant growth. However, the action of HNO in plants has been difficult to understand due to the lack of highly sensitive and real-time in-situ monitoring tools. Herein, we presented a near-infrared fluorescent probe, DCI-HNO, based on dicyanoisophorone fluorophore, for real-time mapping HNO in plants. The introduction of a phosphine moiety as a specific HNO recognition unit can inhibit the intramolecular charge transfer (ICT) of probe DCI-HNO. However, in the presence of HNO, the ICT process occurred, leading to the emission at 665 nm. Probe DCI-HNO exhibited high sensitivity (97 nM), rapid response time (8 min), large Stokes shift (135 nm) for detection of HNO in plants. The novel developed probe has successfully imaged endogenous HNO produced during NO/H2S cross-talk in plant tissues. Additionally, the up-regulated in HNO levels during tobacco aging and in response to stress has been confirmed. Therefore, probe DCI-HNO has provided a reliable method for monitoring the NO/H2S cross-talk and revealing the role of HNO in plants.

Tertiary lymphoid structures predict survival and response to neoadjuvant therapy in locally advanced rectal cancer.

Tertiary lymphoid structure (TLS) contributes to the anti-tumor immune response, and predicts the prognosis of colorectal cancer patients. However, the potential impact of TLS in shaping the immune status of rectal adenocarcinoma, and the intrinsic relationship between TLS and neoadjuvant therapies (neoTx) remain unclear. We performed hematoxylin-eosin staining, immunohistochemical and biomolecular analyses to investigate TLS and tumor-infiltrating lymphocytes (TILs) in 221 neoTx-treated and 242 treatment-naïve locally advanced rectal cancer (LARC) patients. High TLS density was significantly associated with the absence of vascular invasion, a lower neutrophil-to-lymphocyte ratio, increased TLS maturity, a longer recurrence-free survival (RFS) (hazard ratio [HR] 0.2985 95% confidence interval [CI] 0.1894-0.4706, p < 0.0001) and enhanced infiltration of adaptive immune cells. Biomolecular analysis showed that high TLS-score was strongly associated with more infiltration of immune cells and increased activation of immune-related pathways. TLS+ tumors in pre-treatment specimens were associated with a higher proportion of good respond (62.5% vs. 29.8%, p < 0.0002) and pathological complete remission (pCR) (40.0% vs. 11.1%, p < 0.0001), and significantly increased RFS (HR 0.3574 95%CI 0.1489-0.8578 p = 0.0213) compared with TLS- tumors in the neoTx cohort, which was confirmed in GSE119409 and GSE150082. Further studies showed that neoTx significantly reduced TLS density and maturity, and abolished the prognostic value of TLS. Our study illustrates that TLS may have a key role in mediating the T-cell-inflamed tumor microenvironment, which also provides a new direction for neoTx, especially neoadjuvant immunotherapy, in LRAC patients.

3D printed strontium-doped calcium phosphate ceramic scaffold enhances early angiogenesis and promotes bone repair through the regulation of macrophage polarization.

The vascularization of bone repair materials is one of the key issues that urgently need to be addressed in the process of bone repair. The changes in macrophage phenotype and function play an important role in the process of vascularization, and endowing bone repair materials with immune regulatory characteristics to enhance angiogenesis is undoubtedly a new strategy to improve the effectiveness of bone repair. In order to improve the effect of tricalcium phosphate (TCP) on vascularization and bone repair, we doped strontium ions (Sr) into TCP (SrTCP) and prepared porous 3D printed SrTCP scaffolds using 3D printing technology, and studied the scaffold mediated macrophage polarization and subsequent vascularization and bone regeneration. The results of the interaction between the scaffold and macrophages showed that the SrTCP scaffold can promote the polarization of macrophages from M1 to M2 and secrete high concentrations of VEGF and PDGF-bb cytokines, which shows excellent angiogenic potential. When human umbilical vein endothelial cells (HUVECs) were co-cultured with macrophage-conditioned medium of SrTCP scaffold, HUVECs exhibited excellent early angiogenesis-promoting effects in terms of scratch healing, angiogenic gene expression, and in vitro tube formation performance. The results of in vivo bone repair experiments showed that the SrTCP scaffold formed a vascular network with high density and quantity in the bone defect area, which could increase the rate of new bone formation and advance the period of bone formation, and finally achieved a better bone repair effect. We observed a cascade effect in which Sr-doped SrTCP scaffold regulate macrophage polarization to enhance angiogenesis and promote bone repair, which may provide a new strategy for the repair of clinical bone defects.