Early human milk feeding: Relationship to intestinal barrier maturation and postnatal growth.

OBJECTIVES: Early exposure to mother's own milk (MOM) promotes intestinal barrier maturation in preterm infants. We hypothesized (1) donor human milk (DHM) supplementation reduces intestinal permeability (IP) similar to exclusive MOM and (2) early HM exposure and low IP at 7-10 days postnatal age (PNA) are associated with improved growth outcomes. METHODS: IP was measured by the standard sugar absorption test (SAT) in infants <33 weeks gestation between 7-10 days PNA. Nutritional and anthropometric data were recorded. Postnatal growth failure (PNGF) was defined as a decrease in weight z-score >1 from birth to discharge to home. RESULTS: Of 158 preterm infants, the mean (SD) gestational age was 29.9(2.3) weeks and birthweight 1388(424) g. Diet prior to SAT was exclusive MOM [N = 55(35%)], DHM ± MOM [N = 52(33%)], or preterm formula±MOM [N = 51(32%)]. The mean Lactulose(La)/Rhamnose(Rh) ratio was lower in the exclusive MOM [0.06(0.07)] and DBM ± MOM [0.05(0.07)] groups compared to the preterm formula±MOM group [0.11(0.11)], p < 0.01). Cumulative intake >150 ml/kg MOM ± DHM, but not preterm formula within 7-10 days PNA was associated with early intestinal barrier maturation. Low IP was not associated with lower risk of PNGF at discharge. CONCLUSIONS: Low IP is associated with cumulative intake of MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days PNA. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT01756040 ; web link to study on registry: https://clinicaltrials.gov/study/NCT01756040 . IMPACT: Key message Early intestinal barrier maturation is associated with cumulative intake of exclusive MOM alone or supplemented with DHM > 150 ml/kg within 7-10 days after birth, but is not associated with lower risk of PNGF at time of discharge. What it adds to existing literature? This observational study is the first study to demonstrate that supplemental DHM promotes intestinal barrier maturation similar to MOM alone. What is the impact? The findings underscore the importance of early introduction of human milk feeds as MOM or MOM supplemented with DHM in sufficient volume to promote early intestinal barrier maturation.

Comprehensive analysis of a necroptosis-associated diagnostic signature for myelodysplastic syndromes based on single-cell RNA-seq and bulk RNA-seq.

BACKGROUND: Myelodysplastic syndromes (MDS) are heterogeneous and clonal hematological disorders. The role and mechanism of necroptosis in MDS remain poorly understood. METHODS: mRNA expression profiles and single-cell RNA-sequencing (scRNA-seq) data were sourced from the GEO database. ScRNA-seq data were processed using the "Seurat" package. After cell annotation, necroptosis-related scores (NRscores) for each cell were calculated using the "UCell" package. Differentially expressed genes (DEGs) and their associated biological functions in NRscore-related cell populations were identified. Additionally, DEGs and necroptosis-related genes (DE-NRGs) between MDS patients and healthy controls were identified. Consensus clustering was employed to classify MDS patients into distinct subclusters based on DE-NRGs. The biological functions and immune characteristics of these classifications were analyzed. Prognostic gene signatures were determined using LASSO and SVM-RFE analyses, and a nomogram was constructed based on the prognostic gene signature. RESULTS: A total of 12 cell types were identified in MDS and healthy controls. NRscore was found to be elevated in monocytes and common lymphoid precursors (CLPs). Enrichment analysis revealed that monocytes and CLPs with high NRscore were associated with mitochondria-related and immune-related pathways. Eleven DEGs in monocytes and CLPs between MDS patients and healthy controls were identified. Additionally, 13 DE-NRGs were identified from 951 DEGs between MDS and healthy controls. MDS patients were classified into two distinct subclusters based on these 13 DE-NRGs, revealing several immune-related processes and signaling pathways. Differences in immune subpopulations between the two subclusters were observed. A necroptosis-related diagnostic gene signature (IRF9, PLA2G4A, MLKL, BAX, JAK2, and STAT3) was identified as predictive of MDS prevalence. CONCLUSION: Necroptosis plays a role in MDS progression by inducing inflammation. A novel necroptotic gene signature has been developed to distinguish and diagnose MDS at early stages of the disease.

Effect of 0.01% atropine eye drops combined with different optical treatments to control low myopia in Chinese children.

PURPOSE: To investigate the efficacy and safety of 0.01% atropine (AT) in combination with different optical treatments for controlling myopia in Chinese children. METHODS: This retrospective study analyzed 341 Chinese children aged 6-11 years with myopia between -0.50 D and -3.0 D between January 2022 and May 2023. The fast-progressing, myopic children received three optical treatments combined with 0.01 % atropine: 75 children with single-vision spectacles and atropine (SV + AT), 162 children with defocus-incorporated multi-segment spectacles and atropine (DIMS + AT), or 104 children with orthokeratology and atropine (OK + AT). The changes in spherical equivalent refraction (SER), axial length (AL), intraocular pressure (IOP), and amplitude of accommodation (AMP) were observed at 6-month and 1-year intervals. RESULTS: After controlling for baseline variables, at 6 months, the increase in adjusted AL was significantly greater in the SV + AT group than in the DIMS + AT group (difference = 0.13 mm, 95 % CI: 0.07-0.20, P < 0.05) and in the OK + AT group (difference = 0.09 mm, 95 % CI: 0.09-0.17, P < 0.05). A more significant progression in adjusted SER was also observed in the SV + AT group than in the DIMS group (difference = -0.20D, 95 % CI: -0.29 to -0.11, P < 0.05). At 12 months, the greatest increase in adjusted AL was observed in the SV + AT group, with a statistically significant difference of 0.24 mm (95 % CI: 0.19-0.29, P < 0.05) compared with the DIMS group and a difference of 0.19 mm (95 % CI: 0.13-0.25, P < 0.05) compared with the OK + ST group. Similarly, a more significant progression in adjusted SER was observed in the SV + AT group than in the DIMS group (difference = -0.36 D, 95 % CI: -0.48 to -0.24, P < 0.05). CONCLUSIONS: This study suggested that 0.01% atropine combined with DIMS or orthokeratology may be viable for controlling low myopia in fast-progressing, myopic children.

Effect of body mass index on ovarian reserve and ART outcomes in infertile women: a large retrospective study.

BACKGROUND: Obesity poses a significant global health challenge, with profound implications for women's reproductive health. The relationship between ovarian reserve and body mass index (BMI) remains a subject of debate. While obesity is generally associated with poorer outcomes in assisted reproductive technology (ART), the evidence remains inconclusive. This study aimed to investigate the effect of pre-pregnancy BMI on ovarian reserve and ART outcomes in infertile patients. METHODS: We conducted a retrospective cohort study involving women who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures at Tongji Hospital between 2016 and 2023. The study included 30,746 initial fresh cycles and 5,721 singleton deliveries. Patients were stratified by age and further categorized into four BMI groups: lean (< 18.5 kg/m²), normal weight (18.5-24.9 kg/m²), overweight (25.0-29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary endpoints of the study were pregnancy and perinatal outcomes. To explore the association between BMI and these outcomes, we adjusted for relevant confounding factors and utilized multivariate linear regression models, complemented by multifactorial logistic regression analyses. RESULTS: Anti-Müllerian hormone (AMH) levels were significantly lower in the overweight and obese groups compared to the normal weight group. After adjusting for age, a negative correlation was found between AMH and BMI in the age subgroups of 20-30 and 30-35 years. Among women aged 20-35 years, those in the overweight and obese groups had significantly fewer retrieved oocytes, mature oocytes, and two-pronuclear (2PN) embryos than their normal weight counterparts. Despite these differences, pregnancy outcomes in the overweight and obese groups were comparable to those in the normal weight group across all age categories. Additionally, obesity was linked to an increased risk of gestational diabetes mellitus, hypertensive disorders of pregnancy, and macrosomia. CONCLUSIONS: An age-related decrease in AMH levels was evident with increasing BMI. Although being overweight or obese is associated with poorer embryo and perinatal outcomes, it does not seem to have a substantial impact on fertility.

Dynamic Event-Triggered Strategy-Based Optimal Control of Modular Robot Manipulator: A Multiplayer Nonzero-Sum Game Perspective.

Due to the limited computing and processing ability of modular robot manipulator (MRM) components, such as sensors and controllers, event-triggered mechanisms are considered a crucial communication paradigm shift in resource constrained applications. Dynamic event-triggered mechanism is developing into a new technology by reason of its higher resource utilization efficiency and more flexible system design requirements than traditional event-triggered. Therefore, an optimal control scheme of multiplayer nonzero-sum game based on dynamic event-triggered is developed for MRM systems with uncertain disturbances. First, dynamic model of the MRM is established according to joint torque feedback technique and model uncertainty is estimated by data-driven-based neural network identifier. In the framework of differential game, the tracking control problem of MRM system is transformed into the optimal control problem for multiplayer nonzero-sum game with the control input of each joint module as the player. Then, the static event-triggered control problem of MRM system is studied based on adaptive dynamic programming algorithm. On this basis, the internal dynamic variable describing the previous state of the system is introduced, and the characteristics of dynamic trigger rule and its relationship with static rule are revealed theoretically. By designing an exponential attenuation signal, the minimum sampling interval of the system is always positive, so that Zeno behavior is excluded. Lyapunov theory proves that the system is asymptotically stable and the experimental results verify the validity of the proposed method.

Histone modifications and Sp1 promote GPR160 expression in bone cancer pain within rodent models.

Bone cancer pain (BCP) affects ~70% of patients in advanced stages, primarily due to bone metastasis, presenting a substantial therapeutic challenge. Here, we profile orphan G protein-coupled receptors in the dorsal root ganglia (DRG) following tumor infiltration, and observe a notable increase in GPR160 expression. Elevated Gpr160 mRNA and protein levels persist from postoperative day 6 for over 18 days in the affected DRG, predominantly in small-diameter C-fiber type neurons specific to the tibia. Targeted interventions, including DRG microinjection of siRNA or AAV delivery, mitigate mechanical allodynia, cold, and heat hyperalgesia induced by the tumor. Tumor infiltration increases DRG neuron excitability in wild-type mice, but not in Gpr160 gene knockout mice. Tumor infiltration results in reduced H3K27me3 and increased H3K27ac modifications, enhanced binding of the transcription activator Sp1 to the Gpr160 gene promoter region, and induction of GPR160 expression. Modulating histone-modifying enzymes effectively alleviated pain behavior. Our study delineates a novel mechanism wherein elevated Sp1 levels facilitate Gpr160 gene transcription in nociceptive DRG neurons during BCP in rodents.

Perfluorooctane sulfonate (PFOS) and benzo[a]pyrene (BaP) synergistically induce neurotoxicity in C6 rat glioma cells via the activation of neurotransmitter and Cyp1a1-mediated steroid hormone synthesis pathways.

Humans are often exposed to complex mixtures of multiple pollutants rather than a single pollutant. However, the combined toxic effects and the molecular mechanism of PFOS and BaP remain poorly understood. In this study, two typical environmental pollutants, perfluorooctane sulfonate acid (PFOS) and benzo [a]pyrene (BaP), were selected to investigate their combined neurotoxic effects on rat C6 glioma cells at environmentally relevant concentrations. The results showed that coexposure to low-dose PFOS and BaP induced greater toxicity (synergistic effect) than did single exposure. PFOS-BaP coexposure had stronger toxic effects on inducing oxidative stress and promoting early apoptosis. Targeted metabolomics confirmed that increased levels of the neurotransmitters 5-hydroxytryptophan, dopamine, tryptophan and serotonin disturb the phenylalanine, tyrosine and tryptophan biosynthesis pathways. Mechanistically, exposure to a low-dose PFOS-BaP binary mixture induces steroid hormone synthesis disorder through the activation of Cyp1a1 and Hsd17b8 (steroid hormone synthesis genes) and Dhcr24 and Dhcr7 (cholesterol synthesis genes). These findings are useful for comprehensively and systematically elucidating the biological safety of PFOS-BaP and its potential threats to human health.

The Synergistic Effect of Calcained Coal-Series Kaolinite and Limestone on the Hydration of Portland Cement.

Limestone calcined clay cement (LC3) presents a promising alternative material due to its reduced CO2 emissions and superior mechanical properties compared to traditional Portland cement (PC). This study investigates the synergistic effect of calcined coal-series kaolinite (CCK) and limestone (LS) on the hydration behavior of cement, specifically focusing on varying mass ratios. The combination of CCK and LS promotes the formation of strätlingite and carboaluminates, which enhances early-age strength development. Additionally, the inclusion of CCK facilitates the formation of carboaluminates during later stages of hydration. After 56 days of hydration, the content of carboaluminates is over 10%wt. This stimulation of secondary hydration products significantly refines the evolution of pore structure, with the harmful large pores gradually transformed into harmless medium pores and gel pores, leading to marked improvements in compressive strength from 7 to 28 days. Replacing 45% PC with CCK and LS at mass ratio of 7 to 2, the compressive strength of blends reaches 47.2 MPa at 28 days. Overall, the synergistic interaction between CCK and LS presents unique opportunities to minimize the CO2 footprint of the cement industry without compromising early and long-term performance.

Clinical application of the free superficial palmar branch of radial artery flap for soft-tissue reconstruction of distal digital injury.

PURPOSE: The purpose of this study is to retrospect and summarize clinical efficiency and experience of the free superficial palmar branch of radial artery (SPBRA) flap for soft-tissue reconstruction in distal digital injury. METHOD: 13 patients with soft-tissue defect of finger, reconstructed by the free superficial palmar branch of radial artery (SPBRA) flap in our department from January 2020 to January 2022, were reviewed. After 6-12 months of follow-up, evaluated the treatment effect of the fingers reconstructed by SPBRA flap. RESULTS: All the flaps in our series application were survival uneventful, and all the donor sites were closed primarily without complications or obvious scarring. The flaps were soft in texture and satisfactory in appearance and function. The flaps with the median nerve palmar cutaneous branch had a good sensation recovery. Measurement of two-point discrimination (TPD) ranged from 6 to 10 mm. All patients were satisfied with the aesthetic appearance. According to the Evaluation Trial Standards of Upper Limb Partial Function of Hand Surgery of Chinese Medical Association, the results were graded as excellent in 11 cases and good in 2 cases. CONCLUSION: The SPBRA perforator flap has the advantages of simple operation, soft texture, good appearance and function, and is credible and useful for reconstructing various finger injuries.

Effects and individual response of salt substitute intervention on blood pressure in a high-risk stroke population: findings from 4200 participants of the China Salt Substitute and Stroke Study.

Background: The protective effects of salt substitutes on blood pressure are well established, yet the individual variations in response to salt substitutes remain unclear. Our study aims to identify the individuals who derive the greatest benefit from salt substitute interventions. Methods: Our study involved 4200 participants at high-risk of stroke from 120 villages in Liaoning Province, as a sub-study of the Salt Substitute and Stroke Study (SSaSS) trial, with 60 villages receiving a 5-year salt substitute intervention and other 60 villages using regular salt. The baseline and endpoint data on basic demographics, anthropometric measurements, and blood pressures were collected. General linear regressions were applied to assess the hypotensive effect of salt substitute intervention on both systolic blood pressure (SBP) and diastolic blood pressure (DBP), with adjustments for potential confounders using both regression adjustment and inverse probability of treatment weighting (IPTW). Individual treatment effects (ITEs) of the salt substitute were estimated using causal forest and causal tree methods, and a treatment-by-subgroup interaction analysis was conducted to validate the robustness of our findings. Findings: During the 5-year follow-up, the salt substitute group exhibited a significant SBP reduction compared to the regular salt intervention group (ß = -1.86 mmHg, 95% CI: -3.56 to -0.15 mmHg). This reduction remained significant after adjusting for potential confounders (ß = -2.82 mmHg, 95% CI: -4.26 to -1.37 mmHg) and the usage status of antihypertensive medications (ß = -2.60 mmHg, 95% CI: -4.95 to -1.15 mmHg). However, no significant reduction was observed in DBP levels. Moreover, baseline SBP, body mass index (BMI) and age were identified as the top three modifiers of the salt substitute intervention's efficacy on SBP levels. Specifically, individuals with a baseline SBP ≤ 142 mmHg and age ≤ 65 years old (ITE = -3.02 mmHg, 95% CI = -5.97 to -0.07 mmHg) or those with a baseline SBP >142 mmHg and BMI ≤ 28.2 kg m-2 (ITE = -4.36 mmHg, 95% CI = -6.58 to -2.14 mmHg) received greater benefits from salt substitute supplementations in reducing SBP levels, and the treatment-by-subgroup interaction analysis further corroborated these findings (Psalt intervention group×age = 0.03 and Psalt intervention group×BMI = 0.01). Conclusions: Salt substitutes may effectively lower blood pressure in individuals at high-risk of stroke, with the hypotensive effect varying according to individual characteristics. Notably, middle-aged individuals with normotension and non-obese patients with hypertension appear to derive the greatest benefit from salt substitute consumption.

NIR Laser Irradiation Promotes Osteogenic Differentiation of PDLSCs Through the Activation of TRPV1 Channels and Subsequent Calcium Signaling.

Near-infrared (NIR) irradiation has shown potential to stimulate osteogenic differentiation, but the mechanisms are not fully understood. The study is to investigate the effects of NIR laser irradiation on osteoblastic differentiation. Human periodontal ligament stem cells (hPDLSCs) were cultured in osteogenic medium and exposed to 810 nm NIR laser at 0.5 J/cm2 every 48 h. The transient receptor potential vanilloid (TRPV1) channel inhibitor capsazepine (CPZ) was used to evaluate the role of calcium influx. Osteogenic differentiation was assessed by proliferation (CCK-8), alkaline phosphatase (ALP) activity, mineralization (Alizarin Red), and expression of bone markers by PCR and Western blot over 2 weeks. Intracellular calcium was measured by Fluo-4M dye and flow cytometry. Results showed that NIR irradiation enhanced hPDLSC proliferation, ALP activity, mineralization, and bone marker expression, indicating increased osteogenic differentiation. These effects were inhibited by CPZ. NIR induced a transient rise in intracellular calcium peaking at 3 min, which was blocked by CPZ. In conclusion, this study demonstrates that NIR laser irradiation promotes osteogenic differentiation of PDLSCs through the activation of TRPV1 channels and subsequent calcium signaling. Further research is warranted to optimize the treatment parameters and elucidate the detailed signaling pathways involved, paving the way for the clinical application of NIR therapy in the treatment of bone disorders and periodontal disease.

Diagnostic accuracy of artificial intelligence-assisted caries detection: a clinical evaluation.

OBJECTIVE: This clinical study aimed to evaluate the practical value of integrating an AI diagnostic model into clinical practice for caries detection using intraoral images. METHODS: In this prospective study, 4,361 teeth from 191 consecutive patients visiting an endodontics clinic were examined using an intraoral camera. The AI model, combining MobileNet-v3 and U-net architectures, was used for caries detection. The diagnostic performance of the AI model was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, with the clinical diagnosis by endodontic specialists as the reference standard. RESULTS: The overall accuracy of the AI-assisted caries detection was 93.40%. The sensitivity and specificity were 81.31% (95% CI 78.22%-84.06%) and 95.65% (95% CI 94.94%-96.26%), respectively. The NPV and PPV were 96.49% (95% CI 95.84%-97.04%) and 77.68% (95% CI 74.49%-80.58%), respectively. The diagnostic accuracy varied depending on tooth position and caries type, with the highest accuracy in anterior teeth (96.04%) and the lowest sensitivity for interproximal caries in anterior teeth and buccal caries in premolars (approximately 10%). CONCLUSION: The AI-assisted caries detection tool demonstrated potential for clinical application, with high overall accuracy and specificity. However, the sensitivity varied considerably depending on tooth position and caries type, suggesting the need for further improvement. Integration of multimodal data and development of more advanced AI models may enhance the performance of AI-assisted caries detection in clinical practice.

Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis.

Innate immune responses such as phagocytosis are critically linked to the generation of adaptive immune responses against the neoantigens in cancer and the efferocytosis that is essential for homeostasis in diseases characterized by lung injury, inflammation, and remodeling as in chronic obstructive pulmonary disease (COPD). Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it inhibits adaptive immune responses by stimulating immune checkpoint molecules (ICPs) and portends a poor prognosis. CHI3L1 is also induced in COPD where it regulates epithelial cell death. In this study, we demonstrate that pulmonary melanoma metastasis inhibits macrophage phagocytosis by stimulating the CD47-SIRPα and CD24-Siglec10 phagocytosis checkpoint pathways while inhibiting macrophage "eat me" signals from calreticulin and HMGB1. We also demonstrate that these effects on macrophage phagocytosis are associated with CHI3L1 stimulation of the SHP-1 and SHP-2 phosphatases and inhibition of the accumulation and phosphorylation of cytoskeleton-regulating nonmuscle myosin IIa. This inhibition of innate immune responses such as phagocytosis provides a mechanistic explanation for the ability of CHI3L1 to stimulate ICPs and inhibit adaptive immune responses in cancer and diseases such as COPD. The ability of CHI3L1 to simultaneously inhibit innate immune responses, stimulate ICPs, inhibit T cell costimulation, and regulate a number of other oncogenic and inflammation pathways suggests that CHI3L1-targeted therapeutics are promising interventions in cancer, COPD, and other disorders.

Maize Dek51 encodes a DEAD-box RNA helicase essential for pre-rRNA processing and seed development.

Pre-rRNA processing is essential to ribosome biosynthesis. However, the processing mechanism is not fully understood in plants. Here, we report a DEAD-box RNA helicase DEK51 that mediates the 3' end processing of 18S and 5.8S pre-rRNA in maize (Zea mays L.). DEK51 is localized in the nucleolus, and loss of DEK51 arrests maize seed development and blocks the 3' end processing of 18S and 5.8S pre-rRNA. DEK51 interacts with putative key factors in nuclear RNA exosome-mediated pre-rRNA processing, including ZmMTR4, ZmSMO4, ZmRRP44A, and ZmRRP6L2. This suggests that DEK51 facilitates pre-rRNA processing by interacting with the exosome. Loss of ZmMTR4 function arrests seed development and blocks the 3' end processing of 18S and 5.8S pre-rRNA, similar to dek51. DEK51 also interacts with endonucleases ZmUTP24 and ZmRCL1, suggesting that it may also be involved in the cleavage at site A2. These results show the critical role of DEK51 in promoting 3' end processing of pre-rRNA.

Natural Coptidis Rhizoma Nanoparticles Improved the Oral Delivery of Docetaxel.

Purpose: Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract. Methods: DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX's shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines. Results: Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of -20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells. Conclusion: The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines.

Response of soil moisture to rainfall following deep soil drying in China's hilly loess lands.

Deep soil drying is a physical soil phenomenon that has become increasingly characteristic to artificial afforestation on China's Loess Plateau. Current research is largely short of conclusive reports on soil moisture recovery following deep soil drying in afforested lands. In this study, a 10-m deep underground column was constructed at Pengyang Experimental Station in Ningxia. The CS650-CR1000 automatic soil moisture monitoring system and BLJW-4 small meteorological observation stations were used to respectively monitor soil moisture and meteorological conditions in the study area for the period 2014-2019. The local rainfall was classified and the characteristics of soil infiltration analyzed at both monthly and annual scales. The results showed that: i) Deep soil moisture recovery in the semi-arid Loess Plateau region depended mainly on 25-49.9 mm and >50 mm types of rainfall; together accounting for 35.44 % of the precipitation. ii) Deep soil moisture replenishment occurred mainly for the period from April to October. While this accounted for 30.13 % of the precipitation, evaporation loss accounted for 69.87 % of it. With increasing monthly rainfall (Pm), the variation in monthly infiltration depth (Zm) was quadratic in shape - where Zm = -0.0094 Pm2 + 3.7702 Pm (R2 = 0.9577). iii) At the annual scale, deep soil moisture replenishment was mainly driven by year-on-year infiltration water accumulation. This is because a single year precipitation infiltration was not enough to replenish deep soil moisture. The cumulative infiltration depth for 2014-2019 was 180, 260, 400, 700, 1000 > 1000 cm. It suggested that soil water infiltration and deep dry soil recovery occurred at different times under rainfed conditions in the semi-arid loess hills in China. This is key for in-depth studies of the hydrological process in dry soil regions.

Chitinase 3-like-1 (CHI3L1) in the pathogenesis of epidermal growth factor receptor mutant non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) accounts for 85 % of all lung cancers. In NSCLC, 10-20 % of Caucasian patients and 30-50 % of Asian patients have tumors with activating mutations in the Epidermal Growth Factor Receptor (EGFR). A high percentage of these patients exhibit favorable responses to treatment with tyrosine kinase inhibitors (TKI). Unfortunately, a majority of these patients develop therapeutic resistance with progression free survival lasting 9-18 months. The mechanisms that underlie the tumorigenic effects of EGFR and the ability of NSCLC to develop resistance to TKI therapies, however, are poorly understood. Here we demonstrate that CHI3L1 is produced by EGFR activation of normal epithelial cells, transformed epithelial cells with wild type EGFR and cells with cancer-associated, activating EGFR mutations. We also demonstrate that CHI3L1 auto-induces itself and feeds back to stimulate EGFR and its ligands via a STAT3-dependent mechanism(s). Highly specific antibodies against CHI3L1 (anti-CHI3L1/FRG) and TKI, individually and in combination, abrogated the effects of EGFR activation on CHI3L1 and the ability of CHI3L1 to stimulate the EGFR axis. Anti-CHI3L1 also interacted with osimertinib to reverse TKI therapeutic resistance and induce tumor cell death and inhibit pulmonary metastasis while stimulating tumor suppressor genes including KEAP1. CHI3L1 is a downstream target of EGFR that feeds back to stimulate and activate the EGFR axis. Anti-CHI3L1 is an exciting potential therapeutic for EGFR mutant NSCLC, alone and in combination with osimertinib or other TKIs.