Inflammation down regulates stromal cell-derived factor 1α in the early phase of pulpitis.

The key to prevent pulp necrosis in the early stage of pulpitis is to promote tissue repair, which begins with cell migration. Stromal cell-derived factor 1α (SDF-1α) has been proven to promote cell migration. Related research has so far concentrated on the biological effects of SDF-1α while its expression in pulpitis is still unclear. We investigated the effect of inflammation on SDF-1α in dental pulp and the underlying regulatory mechanisms. First, rat pulpitis models were established by exposing pulp. SDF-1α was decreased on the 3rd day but increased on the 7th day. Next, lipopolysaccharide from Porphyromonas gingivalis (Pg.LPS) was applied to dental pulp cells (DPCs). Within 24 h, SDF-1α decreased, but after 48 h, it steadily increased. Similarly, SDF-1α expression in human chronic pulpitis tissues was also increased. To investigate the effect of altered SDF-1α on DPC migration, cell supernatants collected following Pg.LPS treatment were utilized to stimulate DPCs, and the number of migrated cells was correlated with changes in SDF-1α secretion. Finally, we explored the regulatory mechanisms of SDF-1α down-regulation in the early phase of pulpitis. Within 24 h, JNK/c-Jun pathway was activated in DPC inflammation. When JNK pathway was suppressed, SDF-1α rose. Furthermore, tumor necrosis factor receptor 2 (TNFR2) and apoptosis signal-regulated kinase-interacting protein 1 (AIP1) were up-regulated. Knockdown of them abolished Pg.LPS-induced activation of JNK and c-Jun(Ser63) and significantly enhanced SDF-1α. Our findings indicated that in the early phase of pulpitis, inflammation suppressed SDF-1α by up-regulating TNFR2 and AIP1, which activated JNK/c-Jun(Ser63) pathway.

Isolation, synthesis and bioactivity evaluation of isoquinoline alkaloids from Corydalis hendersonii Hemsl. against gastric cancer in vitro and in vivo.

Isoquinoline alkaloid displays significant anti-gastric cancer effects due to its unique structure, which is attracting more and more attention for the development of anti-gastric cancer drugs. In this study, we explore the active components against gastric cancer from the Tibetan Medicine Corydalis hendersonii Hemsl, which is rich in isoquinoline alkaloids. 14 compounds including 2 previously undescribed natural products were obtained. Interestingly, an new active compound displays potent anti-gastric cancer activity. After accomplishing the total syntheses of the active compound and its derivatives, the anti-gastric cancer activity of the active compound was further investigated. In vitro experiments revealed that the active compound significantly attenuated the proliferative capacity, caused G2/M phase arrest, inhibited the cell migration and invasion, and induced cell apoptosis. Mechanistically, the active compound could increase the Bax/Bcl-2 ratio, elevate cytochrome c in the cytosol, and activate caspase-9/3, along with inactivating the upstream PI3K/Akt/mTOR signaling pathway. In addition, the active compound could also cause gastric cancer cell death by inhibiting topoisomerase I activity. More importantly, the anti-gastric cancer activity of the active compound was confirmed in MGC-803 xenograft nude mice in vivo. This work not only promotes the exploitation of Corydalis hendersonii Hemsl., but also provides some experience for discovering new entities from natural sources.

Wnt4 regulates bone metabolism through IKK-NF-κB and ROCK signaling under occlusal traumatic periodontitis.

BACKGROUND AND OBJECTIVE: Occlusal trauma is one of the most important local contributing factors of periodontitis. It has been reported that Wnt4, a noncanonical Wnt ligand, can inhibit osteoclast formation and inflammation and promote bone formation in vivo. However, the prospects of Wnt4 application in occlusal trauma and periodontitis have not yet been described. This study aimed to investigate the function and the corresponding mechanism of Wnt4 to regulate bone metabolism in occlusal trauma and periodontitis. MATERIAL AND METHODS: Osteogenic-induced MC3T3-E1 cells were treated with or without Porphyromonas gingivalis lipopolysaccharide (Pg. LPS) under cyclic uniaxial compressive stress. After treatment with mouse recombinant protein Wnt4 (rWnt4), the expression of osteogenic markers and activation of the IKK-NF-κB signaling pathway were evaluated in vitro. To investigate whether Wnt4 can promote osteogenesis via the ROCK signaling pathway, the expression of RhoA was evaluated in vitro. Finally, we evaluated the change in bone quantity and the activation of the IKK-NF-κB and ROCK signaling in mice with occlusal trauma and periodontitis to demonstrate the therapeutic efficacy of rWnt4 injection. RESULTS: Stimulation of traumatic force and Pg. LPS stimulation suppressed the expression of osteoblast markers, but their expression was rescued after rWnt4 treatment in vitro. In addition, the inhibition of the ROCK signaling pathway induced by force loading was reversed when rWnt4 was applied in vitro. Micro-CT, H&E, and TRAP staining of the mandibles showed increased bone loss in the occlusal trauma-aggravated periodontitis group, whereas it was rescued after rWnt4 injection. The expression levels of IκBα and p65 were upregulated in occlusal trauma and periodontitis-bearing mice, whereas the expression levels of Runx2 and RhoA were downregulated. After rWnt4 injection, remarkably upregulation of Runx2 and RhoA expression was observed in occlusal trauma and periodontitis- bearing mice. CONCLUSION: Wnt4 not only inhibits IKK-NF-κB signaling but also activates ROCK signaling to inhibit osteoclast formation and promote bone regeneration in occlusal trauma and periodontitis-bearing mice.

Discovery of evodiamine derivatives as potential lead antifungal agents for the treatment of superficial fungal infections.

Mycosis, especially superficial fungal infections (SFIs), has been a serious threat to humans in recent years. Evodiamine (EVO), as an effective component of the Traditional Chinese Medicine Evodia rutaecarpa, has good antibacterial effects and low toxicity. In order to find out the potential therapeutic agents against SFIs, a series of EVO derivatives were synthesized and systematic evaluations of antifungal activity were carried out. Among them, compound A7 exhibited great antifungal activity with the values of MIC100 were 38, 38 and 2 µg/mL, respectively, against T. rubrum, T. mentagrophytes and C. albicans, and even stronger than that of ketoconazole (KCZ) with the values of MIC100 were 106, 106 and 3 µg/mL, respectively. Further antifungal evaluations in vitro verified that compound A7 indeed had favorable antifungal activity. Moreover, compound A7 could exert excellent antifungal effect on T. rubrum-infected guinea pigs, suggesting that A7 was an attractive molecule and could be a potential lead compound for the development of anti-fungal agents, and providing a great promising therapeutic strategy for fungal disease.

COX5A over-expression protects cortical neurons from hypoxic ischemic injury in neonatal rats associated with TPI up-regulation.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) represents as a major cause of neonatal morbidity and mortality. However, the underlying molecular mechanisms in brain damage are still not fully elucidated. This study was conducted to determine the specific potential molecular mechanism in the hypoxic-ischemic induced cerebral injury. METHODS: Here, hypoxic-ischemic (HI) animal models were established and primary cortical neurons were subjected to oxygen-glucose deprivation (OGD) to mimic HIE model in vivo and in vitro. The HI-induced neurological injury was evaluated by Zea-longa scores, Triphenyte-trazoliumchloride (TTC) staining the Terminal Deoxynucleotidyl Transferased Utp Nick End Labeling (TUNEL) and immunofluorescent staining. Then the expression of Cytochrome c oxidase subunit 5a (COX5A) was determined by immunohistochemistry, western blotting (WB) and quantitative real time Polymerase Chain Reaction (qRT-PCR) techniques. Moreover, HSV-mediated COX5A over-expression virus was transducted into OGD neurons to explore the role of COX5A in vitro, and the underlying mechanism was predicted by GeneMANIA, then verified by WB and qRT-PCR. RESULTS: HI induced a severe neurological dysfunction, brain infarction, and cell apoptosis as well as obvious neuron loss in neonatal rats, in corresponding to the decrease on the expression of COX5A in both sides of the brain. What's more, COX5A over-expression significantly promoted the neuronal survival, reduced the apoptosis rate, and markedly increased the neurites length after OGD. Moreover, Triosephosephate isomerase (TPI) was predicted as physical interactions with COX5A, and COX5A over-expression largely increased the expressional level of TPI. CONCLUSIONS: The present findings suggest that COX5A plays an important role in promoting neurological recovery after HI, and this process is related to TPI up-regulation.

Physician code creep after the initiation of outpatient volume control program and implications for appropriate ICD-10-CM coding.

BACKGROUND: Most studies on the physician code creep (i.e., changes in case mix record-keeping practices to improve reimbursement) have focused on episodes (inpatient hospitalizations or outpatient procedures). Little is known regarding changes in diagnostic coding practices for better reimbursement among a fixed cohort of patients with chronic diseases. METHODS: To examine whether physicians in tertiary medical centers changed their coding practices after the initiation of the Outpatient Volume Control Program (OVCP) in Taiwan, we conducted a retrospective observational study of four patient cohorts (two interventions and two controls) from January 2016 to September 2017 in Taiwan. The main outcomes were the number of outpatient visits with four coding practices: 1) OVCP monitoring code recorded as primary diagnosis; 2) OVCP monitoring code recorded as secondary diagnosis; 3) non-OVCP monitoring code recorded as primary diagnosis; 4) non-OVCP monitoring code recorded as secondary diagnosis. RESULTS: The percentage change of the number of visits with coding practice 1 between 2016Q1 and 2017Q3 was - 74% for patients with hypertension and - 73% with diabetes in tertiary medical centers and - 23% and - 17% in clinics, respectively. By contrast, the percentage changes of coding practice 3 were + 73% for patients with hypertension and + 46% for patients with diabetes in tertiary medical centers and - 19% and - 2% in clinics, respectively. CONCLUSIONS: Physician code creep occurred after the initiation of the OVCP. Education regarding appropriate outpatient coding for physicians will be relatively effective when proper coding is related to reimbursement.

Identification of Fusarium Head Blight in Winter Wheat Ears Using Continuous Wavelet Analysis.

Fusarium head blight in winter wheat ears produces the highly toxic mycotoxin deoxynivalenol (DON), which is a serious problem affecting human and animal health. Disease identification directly on ears is important for selective harvesting. This study aimed to investigate the spectroscopic identification of Fusarium head blight by applying continuous wavelet analysis (CWA) to the reflectance spectra (350 to 2500 nm) of wheat ears. First, continuous wavelet transform was used on each of the reflectance spectra and a wavelet power scalogram as a function of wavelength location and the scale of decomposition was generated. The coefficient of determination R2 between wavelet powers and the disease infestation ratio were calculated by using linear regression. The intersections of the top 5% regions ranking in descending order based on the R2 values and the statistically significant (p-value of t-test < 0.001) wavelet regions were retained as the sensitive wavelet feature regions. The wavelet powers with the highest R2 values of each sensitive region were retained as the initial wavelet features. A threshold was set for selecting the optimal wavelet features based on the coefficient of correlation R obtained via the correlation analysis among the initial wavelet features. The results identified six wavelet features which include (471 nm, scale 4), (696 nm, scale 1), (841 nm, scale 4), (963 nm, scale 3), (1069 nm, scale 3), and (2272 nm, scale 4). A model for identifying Fusarium head blight based on the six wavelet features was then established using Fisher linear discriminant analysis. The model performed well, providing an overall accuracy of 88.7% and a kappa coefficient of 0.775, suggesting that the spectral features obtained using CWA can potentially reflect the infestation of Fusarium head blight in winter wheat ears.

Synthesis and biological evaluation of 4,6-diaryl-2-pyrimidinamine derivatives as anti-breast cancer agents.

Breast cancer is the most frequently diagnosed cancers and the leading causes of cancer death among females worldwide. Estrogen receptor positive has been identified as the predominant internal reasons, involving in more than 70% breast cancer patients and SERMs which competes with estradiol for the binding to ERα in breast tissue are widely used in the treatment of ER+ breast cancer, such as tamoxifen, raloxifene. However, many SERMs may cause negative side effects due to their estrogenic activity in other tissues and approximate 50% of patients with ER-positive tumors either initially do not respond or become resistant to these drugs. Here, a series of designed 4,6-diaryl-2-pyrimidinamine derivatives had been synthesized to treat estrogen receptor positive breast cancer by simultaneously antagonizing ER and inhibiting VEGFR-2. Bioactivity evaluation showed that these compounds could significantly inhibit the proliferation of MCF-7, HUVEC and Ishikawa cells. Further studies identified compound III-3A could antagonize against estrogen action and inhibit the phosphorylation of VEGFR-2 as well as inhibit angiogenesis in vivo. The results indicated designed 4,6-diaryl-2-pyrimidinamine derivatives can be used to further study as anti-breast cancer drugs.

Structure-guided design and synthesis of isoflavone analogs of GW4064 with potent lipid accumulation inhibitory activities.

Our group has previously reported a series of isoflavone derivatives with antidyslipidemic activity. With this background, a series of isoflavone analogs of GW4064 were designed, synthesized and evaluated the lipid-lowering activity of analogs. As a result, most of compounds significantly reduced the lipid accumulation in 3T3-L1 adipocytes and four of them (10a, 11, 15c and 15d) showed stronger inhibitory than GW4064. The most potent compound 15d exhibited promising agonistic activity for FXR in a cell-based luciferase reporter assay. Meanwhile, 15d up-regulated FXR, SHP and BSEP gene expression and down-regulated the mRNA expression of lipogenesis gene SREBP-1c. Besides, an improved safety profile of 15d was also observed in a HepG2 cytotoxicity assay compared with GW4064. The obtained biological results were further confirmed by a molecular docking study showing that 15d fitted well in the binding pocket of FXR and interacted with some key residues simultaneously.

Design and synthesis of benzofuro[3,2-b]pyridin-2(1H)-one derivatives as anti-leukemia agents by inhibiting Btk and PI3Kδ.

Btk inhibitors and PI3Kδ inhibitors play crucial roles in the treatment of leukemia, and studies confirmed that the synergetic inhibition against Btk and PI3Kδ could gain an optimal response. Herein, a series of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives were designed and synthesized as dual Btk/PI3Kδ kinases inhibitors for the treatment of leukemia. Studies indicated that most compounds could suppress the proliferation of multiple leukemia or lymphoma cells (Raji, HL60 and K562 cells) at low micromolar concentrations in vitro. Further kinase assays identified several compounds could simultaneously inhibit Btk kinase and PI3Kδ kinase. Thereinto, compound 16b exhibited the best inhibitory activity (Btk: IC50 = 139 nM; PI3Kδ: IC50 = 275 nM) and showed some selectivity against PI3Kδ compared to PI3Kß/γ. Finally, the SAR of target compounds was preliminarily discussed combined with docking results. In brief, 16b possessed of the potency for the further optimization as anti-leukemia drugs by inhibiting simultaneously Btk kinase and PI3Kδ kinase.

New Spectral Index for Detecting Wheat Yellow Rust Using Sentinel-2 Multispectral Imagery.

Yellow rust is one of the most destructive diseases for winter wheat and has led to a significant decrease in winter wheat quality and yield. Identifying and monitoring yellow rust is of great importance for guiding agricultural production over large areas. Compared with traditional crop disease discrimination methods, remote sensing technology has proven to be a useful tool for accomplishing such a task at large scale. This study explores the potential of the Sentinel-2 Multispectral Instrument (MSI), a newly launched satellite with refined spatial resolution and three red-edge bands, for discriminating between yellow rust infection severities (i.e., healthy, slight, and severe) in winter wheat. The corresponding simulative multispectral bands for the Sentinel-2 sensor were calculated by the sensor's relative spectral response (RSR) function based on the in situ hyperspectral data acquired at the canopy level. Three Sentinel-2 spectral bands, including B4 (Red), B5 (Re1), and B7 (Re3), were found to be sensitive bands using the random forest (RF) method. A new multispectral index, the Red Edge Disease Stress Index (REDSI), which consists of these sensitive bands, was proposed to detect yellow rust infection at different severity levels. The overall identification accuracy for REDSI was 84.1% and the kappa coefficient was 0.76. Moreover, REDSI performed better than other commonly used disease spectral indexes for yellow rust discrimination at the canopy scale. The optimal threshold method was adopted for mapping yellow rust infection at regional scales based on realistic Sentinel-2 multispectral image data to further assess REDSI's ability for yellow rust detection. The overall accuracy was 85.2% and kappa coefficient was 0.67, which was found through validation against a set of field survey data. This study suggests that the Sentinel-2 MSI has the potential for yellow rust discrimination, and the newly proposed REDSI has great robustness and generalized ability for yellow rust detection at canopy and regional scales. Furthermore, our results suggest that the above remote sensing technology can be used to provide scientific guidance for monitoring and precise management of crop diseases and pests.

Integrating Early Growth Information to Monitor Winter Wheat Powdery Mildew Using Multi-Temporal Landsat-8 Imagery.

Powdery mildew is one of the dominant diseases in winter wheat. The accurate monitoring of powdery mildew is important for crop management and production. Satellite-based remote sensing monitoring has been proven as an efficient tool for regional disease detection and monitoring. However, the information provided by single-date satellite scene is hard to achieve acceptable accuracy for powdery mildew disease, and incorporation of early period contextual information of winter wheat can improve this situation. In this study, a multi-temporal satellite data based powdery mildew detecting approach had been developed for regional disease mapping. Firstly, the Lansat-8 scenes that covered six winter wheat growth periods (expressed in chronological order as periods 1 to 6) were collected to calculate typical vegetation indices (VIs), which include disease water stress index (DSWI), optimized soil adjusted vegetation index (OSAVI), shortwave infrared water stress index (SIWSI), and triangular vegetation index (TVI). A multi-temporal VIs-based k-nearest neighbors (KNN) approach was then developed to produce the regional disease distribution. Meanwhile, a backward stepwise elimination method was used to confirm the optimal multi-temporal combination for KNN monitoring model. A classification and regression tree (CART) and back propagation neural networks (BPNN) approaches were used for comparison and validation of initial results. VIs of all periods except 1 and 3 provided the best multi-temporal data set for winter wheat powdery mildew monitoring. Compared with the traditional single-date (period 6) image, the multi-temporal images based KNN approach provided more disease information during the disease development, and had an accuracy of 84.6%. Meanwhile, the accuracy of the proposed approach had 11.5% and 3.8% higher than the multi-temporal images-based CART and BPNN models', respectively. These results suggest that the use of satellite images for early critical disease infection periods is essential for improving the accuracy of monitoring models. Additionally, satellite imagery also assists in monitoring powdery mildew in late wheat growth periods.

Identification of Wheat Yellow Rust Using Optimal Three-Band Spectral Indices in Different Growth Stages.

Yellow rust, a widely known destructive wheat disease, affects wheat quality and causes large economic losses in wheat production. Hyperspectral remote sensing has shown potential for the detection of plant disease. This study aimed to analyze the spectral reflectance of the wheat canopy in the range of 350⁻1000 nm and to develop optimal spectral indices to detect yellow rust disease in wheat at different growth stages. The sensitive wavebands of healthy and infected wheat were located in the range 460⁻720 nm in the early-mid growth stage (from booting to anthesis), and in the ranges 568⁻709 nm and 725⁻1000 nm in the mid-late growth stage (from filling to milky ripeness), respectively. All possible three-band combinations over these sensitive wavebands were calculated as the forms of PRI (Photochemical Reflectance Index) and ARI (Anthocyanin Reflectance Index) at different growth stages and assessed to determine whether they could be used for estimating the severity of yellow rust disease. The optimal spectral index for estimating wheat infected by yellow rust disease was PRI (570, 525, 705) during the early-mid growth stage with R² of 0.669, and ARI (860, 790, 750) during the mid-late growth stage with R² of 0.888. Comparison of the proposed spectral indices with previously reported vegetation indices were able to satisfactorily discriminate wheat yellow rust. The classification accuracy for PRI (570, 525, 705) was 80.6% and the kappa coefficient was 0.61 in early-mid growth stage, and the classification accuracy for ARI (860, 790, 750) was 91.9% and the kappa coefficient was 0.75 in mid-late growth stage. The classification accuracy of the two indices reached 84.1% and 93.2% in the early-mid and mid-late growth stages in the validated dataset, respectively. We conclude that the three-band spectral indices PRI (570, 525, 705) and ARI (860, 790, 750) are optimal for monitoring yellow rust infection in these two growth stages, respectively. Our method is expected to provide a technical basis for wheat disease detection and prevention in the early-mid growth stage, and the estimation of yield losses in the mid-late growth stage.

PTH and the Regulation of Mesenchymal Cells within the Bone Marrow Niche.

Parathyroid hormone (PTH) plays a pivotal role in maintaining calcium homeostasis, largely by modulating bone remodeling processes. Its effects on bone are notably dependent on the duration and frequency of exposure. Specifically, PTH can initiate both bone formation and resorption, with the outcome being influenced by the manner of PTH administration: continuous or intermittent. In continuous administration, PTH tends to promote bone resorption, possibly by regulating certain genes within bone cells. Conversely, intermittent exposure generally favors bone formation, possibly through transient gene activation. PTH's role extends to various aspects of bone cell activity. It directly influences skeletal stem cells, osteoblastic lineage cells, osteocytes, and T cells, playing a critical role in bone generation. Simultaneously, it indirectly affects osteoclast precursor cells and osteoclasts, and has a direct impact on T cells, contributing to its role in bone resorption. Despite these insights, the intricate mechanisms through which PTH acts within the bone marrow niche are not entirely understood. This article reviews the dual roles of PTH-catabolic and anabolic-on bone cells, highlighting the cellular and molecular pathways involved in these processes. The complex interplay of these factors in bone remodeling underscores the need for further investigation to fully comprehend PTH's multifaceted influence on bone health.

Calorie Restriction in Mice Impairs Cortical but not Trabecular Peak Bone Mass by Suppressing Bone Remodeling.

Calorie restriction (CR) can lead to weight loss and decreased substrate availability for bone cells. Ultimately, this can lead to impaired peak bone acquisition in children and adolescence and bone loss in adults. But the mechanisms that drive diet-induced bone loss in humans are not well characterized. To explore those in greater detail, we examined the impact of 30% calorie restriction for 4 and 8 weeks in both male and female 8-week-old C57BL/6 J mice. Body composition, areal bone mineral density (aBMD), skeletal microarchitecture by micro-CT, histomorphometric parameters, and in vitro trajectories of osteoblast and adipocyte differentiation were examined. After both 4 weeks and 8 weeks, CR mice lost weight and exhibited lower femoral and whole-body aBMD vs. ad libitum (AL) mice. By micro-CT, CR mice had lower cortical bone area fraction vs. AL mice, but males had preserved trabecular bone parameters and females showed increased bone volume fraction compared to AL mice after 8 weeks. Histomorphometric analysis revealed that CR mice had a profound suppression in trabecular as well as endocortical and periosteal bone formation in addition to reduced bone resorption compared to AL mice. Bone marrow adipose tissue was significantly increased in CR mice vs. AL mice. In vitro, the pace of adipogenesis in bone marrow stem cells was greatly accelerated with higher markers of adipocyte differentiation and more oil red O staining, whereas osteogenic differentiation was reduced. qRT-PCR and western blotting suggested that the expression of Wnt16 and the canonical ß-catenin pathway were compromised during CR. In sum, CR causes impaired peak cortical bone mass due to a profound suppression in bone remodeling. The increase in marrow adipocytes in vitro and in vivo is related to both progenitor recruitment and adipogenesis in the face of nutrient insufficiency. Long-term calorie restriction may lead to lower bone mass principally in the cortical envelope, possibly due to impaired Wnt signaling.

Calorie restriction led to impaired bone mass and increased accumulation of bone marrow adipose tissue. During the development of bone-fat imbalance due to calorie restriction, bone remodeling was notably inhibited. Calorie restriction may shift the differentiation of bone marrow stem cells towards adipocytes instead of osteoblasts. This process involves a disruption in the canonical Wnt signaling pathway.

Photoselectively modulating main products by changing the wavelength of visible light over D-π-A-D conjugated polymers.

The diversity of catalytic products determines the difficulty of selective product modulation, which usually relies on adjusting the catalyst and reaction conditions to obtain different main products selectively. Herein, we synthesized D-π-A-D conjugated organic polymers (TH-COP) using cyclotriphosphonitrile, alkyne, 2H-benzimidazole, and sulfur units as electron donors, π bridges, electron acceptors, and electron donors, respectively. TH-COP exhibited excellent photoinduced carrier separation and redox ability under different visible light wavelengths, and the main products of its CO2 reduction are CH4 (1000.0 µmol g-1) and CO (837.0 µmol g-1) under 400-420 nm and 420-560 nm, respectively. In addition, TH-COP could completely convert phenylmethyl sulfide to methyl phenyl sulfone at 400-420 nm and diphenyl disulfide at 480-485 nm in yields up to 95 %. This study presents a novel strategy for the targeted fabrication of various main products using conjugated polymers by simply changing the wavelength range of visible light.

New Insights into Calorie Restriction Induced Bone Loss.

Caloric restriction (CR) is now a popular lifestyle choice due to its ability in experimental animals to improve lifespan, reduce body weight, and lessen oxidative stress. However, more and more emerging evidence suggests this treatment requires careful consideration because of its detrimental effects on the skeletal system. Experimental and clinical studies show that CR can suppress bone growth and raise the risk of fracture, but the specific mechanisms are poorly understood. Reduced mechanical loading has long been thought to be the primary cause of weight loss-induced bone loss from calorie restriction. Despite fat loss in peripheral depots with calorie restriction, bone marrow adipose tissue (BMAT) increases, and this may play a significant role in this pathological process. Here, we update recent advances in our understanding of the effects of CR on the skeleton, the possible pathogenic role of BMAT in CR-induced bone loss, and some strategies to mitigate any potential side effects on the skeletal system.

An Evaluation of the Crop Preference and Phenotypic Characteristics of Ceracris kiangsu Tsai (Orthoptera: Arcypteridae) under Different Temperatures.

The yellow-spined bamboo locust (YSBL), Ceracris kiangsu Tsai, has historically had a significant impact on different bamboo varieties in East Asia and Southeast Asia. Since 2014, there have been many outbreaks of YSBL populations in Laos, and YSBLs subsequently invaded Southwest China in 2020 and 2023. However, there was limited information about the damage to staple crops. Life table parameters and fitness parameters were assessed using wheat, rice, waxy maize, and sweet maize under three different temperatures (25 °C, 30 °C, and 35 °C) in the laboratory. The results indicated that the YSBLs feeding on wheat seedlings displayed a significantly higher survival rate, a shorter developmental time, and a higher adult emergence rate compared to YSBLs feeding on the other host species at 30 °C. The developmental durations of 1st and 3rd instar YSBLs on wheat (1st: 8.21 ± 0.35 d; 3rd: 6.32 ± 0.34 d) and rice (1st: 7.19 ± 0.23 d; 3rd: 9.00 ± 0.66 d) were significantly shorter than those of 1st and 3rd instar YSBLs on waxy maize (1st: 13.62 ± 1.22 d; 3rd: 13.67 ± 6.33 d) and sweet maize (1st: 16.00 ± 1.79 d; 3rd: 18.00 ± 3.49 d) at 30 °C. The body lengths of male and female YSBLs on wheat (male: 29.52 ± 0.40 mm, female: 34.97 ± 0.45 mm) and rice (male: 28.85 ± 0.68 mm, female: 34.66 ± 0.35 mm) were significantly longer than those observed when they were fed on sweet maize (male: 25.64 ± 1.60 mm, female: 21.93 ± 6.89 mm). There were only male adults obtained on waxy maize. The phenotypic characteristics of the YSBLs feeding on rice seedlings were very close to those of the YSBLs feeding on wheat seedlings. A relatively slower decline was observed in the survival rates of YSBL nymphs on wheat and rice compared to those on waxy maize and sweet maize at 25 °C, 30 °C, and 35 °C. In short, this study implied that YSBLs prefer wheat and rice. This study is the first report of direct damage caused by the YSBL to wheat in the laboratory, and its results could be useful in improving our understanding of the host preference of the YSBL and providing strategies for the management of this pest in field crops.

Design, synthesis and biological evaluation of novel quinazolinone derivatives as CRBN E3 ligase modulators.

CRBN E3 ligase modulators, also anteriorly called immunomodulatory drugs (IMiDs), exhibit excellent pharmacological activity by degrading cereblon (CRBN) associated multiple substrates and have become an important field for drug development. These modulators such as Thalidomide, Lenalidomide and CC-122 abduct CRBN to adhere to IKZF1/3 and other neosubstrates, and then induce the degradation of these substrates, thus retarding the further development of related diseases. Herein, we reported a series of CC-122 derivatives that inhibit the proliferation of hematological malignant tumor cell lines. Studies further confirmed that several derivatives which exhibit strong anti-proliferation effect induce the significant degradation of IKZF1/3. In addition, we found that the best compound 14 (SIAIS355035) exhibits better degradation activity and better anti-proliferation activities than CC-122, especially in diffuse large B lymphoma cell lines. Moreover, the PK properties of compound 14 are pretty promising with excellent oral bioavailability. These results clarified the SAR of CC-122 derivatives preliminarily and suggested that compound 14 has great value for further studies as an ideal novel CRBN E3 ligase modulation drug.

Targeting Bcl-xL is a potential therapeutic strategy for extranodal NK/T cell lymphoma.

Extranodal natural killer/T cell lymphoma, nasal type (ENKTL) is an aggressive lymphoid malignancy with a poor prognosis and lacks standard treatment. Targeted therapies are urgently needed. Here we systematically investigated the druggable mechanisms through chemogenomic screening and identified that Bcl-xL-specific BH3 mimetics effectively induced ENKTL cell apoptosis. Notably, the specific accumulation of Bcl-xL, but not other Bcl-2 family members, was verified in ENKTL cell lines and patient tissues. Furthermore, Bcl-xL high expression was shown to be closely associated with worse patient survival. The critical role of Bcl-xL in ENKTL cell survival was demonstrated utilizing selective inhibitors, genetic silencing, and a specific degrader. Additionally, the IL2-JAK1/3-STAT5 signaling was implicated in Bcl-xL dysregulation. In vivo, Bcl-xL inhibition reduced tumor burden, increased apoptosis, and prolonged survival in ENKTL cell line xenograft and patient-derived xenograft models. Our study indicates Bcl-xL as a promising therapeutic target for ENKTL, warranting monitoring in ongoing clinical trials by targeting Bcl-xL.