LINC00982-encoded protein PRDM16-DT regulates CHEK2 splicing to suppress colorectal cancer metastasis and chemoresistance.

Metastasis is one of the key factors of treatment failure in late-stage colorectal cancer (CRC). Metastatic CRC frequently develops resistance to chemotherapeutic agents. This study aimed to identify the novel regulators from "hidden" proteins encoded by long noncoding RNAs (lncRNAs) involved in tumor metastasis and chemoresistance. Methods: CRISPR/Cas9 library functional screening was employed to identify the critical suppressor of cancer metastasis in highly invasive CRC models. Western blotting, immunofluorescence staining, invasion, migration, wound healing, WST-1, colony formation, gain- and loss-of-function experiments, in vivo experimental metastasis models, multiplex immunohistochemical staining, immunohistochemistry, qRT-PCR, and RT-PCR were used to assess the functional and clinical significance of FOXP3, PRDM16-DT, HNRNPA2B1, and L-CHEK2. RNA-sequencing, co-immunoprecipitation, qRT-PCR, RT-PCR, RNA affinity purification, RNA immunoprecipitation, MeRIP-quantitative PCR, fluorescence in situ hybridization, chromatin immunoprecipitation and luciferase reporter assay were performed to gain mechanistic insights into the role of PRDM16-DT in cancer metastasis and chemoresistance. An oxaliplatin-resistant CRC cell line was established by in vivo selection. WST-1, colony formation, invasion, migration, Biacore technology, gain- and loss-of-function experiments and an in vivo experimental metastasis model were used to determine the function and mechanism of cimicifugoside H-1 in CRC. Results: The novel protein PRDM16-DT, encoded by LINC00982, was identified as a cancer metastasis and chemoresistance suppressor. The down-regulated level of PRDM16-DT was positively associated with malignant phenotypes and poor prognosis of CRC patients. Transcriptionally regulated by FOXP3, PRDM16-DT directly interacted with HNRNPA2B1 and competitively decreased HNRNPA2B1 binding to exon 9 of CHEK2, resulting in the formation of long CHEK2 (L-CHEK2), subsequently promoting E-cadherin secretion. PRDM16-DT-induced E-cadherin secretion inhibited fibroblast activation, which in turn suppressed CRC metastasis by decreasing MMP9 secretion. Cimicifugoside H-1, a natural compound, can bind to LEU89, HIS91, and LEU92 of FOXP3 and significantly upregulated PRDM16-DT expression to repress CRC metastasis and reverse oxaliplatin resistance. Conclusions: lncRNA LINC00982 can express a new protein PRDM16-DT to function as a novel regulator in cancer metastasis and drug resistance of CRC. Cimicifugoside H-1 can act on the upstream of the PRDM16-DT signaling pathway to alleviate cancer chemoresistance.

Diagnosis of pulmonary Scedosporium apiospermum infection from bronchoalveolar lavage fluid by metagenomic next-generation sequencing in an immunocompetent female patient with normal lung structure: a case report and literature review.

BACKGROUND: Scedosporium apiospermum (S. apiospermum) belongs to the asexual form of Pseudallescheria boydii and is widely distributed in various environments. S. apiospermum is the most common cause of pulmonary infection; however, invasive diseases are usually limited to patients with immunodeficiency. CASE PRESENTATION: A 54-year-old Chinese non-smoker female patient with normal lung structure and function was diagnosed with pulmonary S. apiospermum infection by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). The patient was admitted to the hospital after experiencing intermittent right chest pain for 8 months. Chest computed tomography revealed a thick-walled cavity in the upper lobe of the right lung with mild soft tissue enhancement. S. apiospermum was detected by the mNGS of BALF, and DNA sequencing reads were 426. Following treatment with voriconazole (300 mg q12h d1; 200 mg q12h d2-d20), there was no improvement in chest imaging, and a thoracoscopic right upper lobectomy was performed. Postoperative pathological results observed silver staining and PAS-positive oval spores in the alveolar septum, bronchiolar wall, and alveolar cavity, and fungal infection was considered. The patient's symptoms improved; the patient continued voriconazole for 2 months after surgery. No signs of radiological progression or recurrence were observed at the 10-month postoperative follow-up. CONCLUSION: This case report indicates that S. apiospermum infection can occur in immunocompetent individuals and that the mNGS of BALF can assist in its diagnosis and treatment. Additionally, the combined therapy of antifungal drugs and surgery exhibits a potent effect on the disease.

1α,25(OH)2D3 ameliorates insulin resistance by alleviating γδ T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression.

Background: Chronic inflammation caused by immune cells is the central link between obesity and insulin resistance. Targeting the inflammatory process is a highly promising method for reversing systemic insulin resistance. Methods: Blood samples were prospectively collected from 68 patients with type 2 diabetes. C57BL/6J mice were fed either a high-fat diet (HFD) or normal chow (NC). We performed phenotypical and functional analyses of immune cells using flow cytometry. Vitamin D receptor (VDR) knockout γδ T cells were constructed using Cas9-gRNA targeted approaches to identify 1α,25(OH)2D3/VDR signaling pathway-mediated transcriptional regulation of fructose-1,6-bisphosphatase (FBP1) in γδ T cells. Results: Serum vitamin D deficiency aggravates inflammation in circulating γδ T cells in type 2 diabetes patients. We defined a critical role for 1α,25(OH)2D3 in regulating glycolysis metabolism, protecting against inflammation, and alleviating insulin resistance. Mechanistically, 1α,25(OH)2D3-VDR promoted FBP1 expression to suppress glycolysis in γδ T cells, thereby inhibiting Akt/p38 MAPK phosphorylation and reducing inflammatory cytokine production. Notably, therapeutic administration of 1α,25(OH)2D3 restrained inflammation in γδ T cells and ameliorated systemic insulin resistance in obese mice. Conclusions: Collectively, these findings show that 1α,25(OH)2D3 plays an important role in maintaining γδ T cell homeostasis by orchestrating metabolic programs, and is a highly promising target for preventing obesity, inflammation, and insulin resistance.

Effects and Mechanisms of Cu Species in Fe-MOFs on Fenton-Like Catalytic Activity and Stability.

Fe-based MOFs (Fe-MOFs) are deemed promising Fenton-like catalysts due to their well-developed pores and accessible active sites. However, their inferior catalytic activity, iron leaching, and low H2O2 utilization always hinder their application as Fe-based MOF catalysts. In this work, we manipulated the structure of Fe-oxo nodes in MIL-88B(Fe) via a CuI species substitution method, affording a mixed-valence (Cu-incorporated Fe-MOFs) with highly improved Fenton-like performance. It is found that the CuI serves as a shuttle to promote transfer between FeII/FeIII, inducing the formation of a larger amount of stable FeII sites, which was proven by experimental and DFT calculation results. A linear relationship was observed for the Fenton-like performance and the amount of CuI species for the catalysts. The corresponding value of the •OH formation is 2.17 eV for Cu-incorporated MIL-88B(Fe), which is significantly lower than that of MIL-88B(Fe) (2.69 eV). Meanwhile, the enriched CuI species suppress Fe species leaching during the catalytic reaction. The Fe-ion leakage of 0.4Cu@MIL-88B is very tiny (0.01-0.03 mg/L), significantly less than that of MIL-88B (2.00-3.02 mg/L). At the same time, H2O2 utilization for 0.4Cu@ MIL-88B(Fe) is 88%, which is almost 4.4 times that of pure MIL-88B(Fe). This work provides insights into the rational design of Fe-MOFs as promising Fenton-like catalysts for wastewater treatment.

The change of amino acids samples under metalimnetic oxygen minimum condition: Characterization and mechanism.

The metalimnetic oxygen minimum (MOM) is a common anaerobic phenomenon that occur between 5.00 and 40.00 m of reservoirs. Amino acids (AAs) are widely found in water, but their change in MOM remain unclear. In this study, four AAs with different side chain groups were selected to explore the change of their samples and related disinfection by-products formation potential (DBPFPs) under MOM condition. The results showed that the final degradation rate of dissolved organic carbon and dissolved organic nitrogen of four AAs samples were 11.71%-59.87% and 26.50%-100.00% under MOM condition. Aspartic acid samples were the easiest to be degraded, whereas glycine samples were the opposite. While the total fluorescence intensity increased by 6.30%-113.40% for the appearance of tryptophan-like substance. The total DBPFPs of glutamic acid, arginine and aspartic acid samples were finally decreased by 4.73%, 8.00% and 98.88% (glycine sample increased by 2.30 times). Compared with the surface condition, the degradation of AAs samples and the change of DBPFPs were significantly inhibited under MOM condition. In addition, the diversities of bacterial communities were significantly reduced under MOM condition, which was very unfavorable to the degradation of AAs samples, and in turn affected the control of DBPs and deteriorated the water quality.

The three-dimensionally ordered microporous CaTiO3 coupling Zn0.3Cd0.7S quantum dots for simultaneously enhanced photocatalytic H2 production and glucose conversion.

Glucose conversion assisted photocatalytic water splitting technology to simultaneously produce H2 and high value-added chemicals is a promising method for alleviating the energy shortage and environmental crisis. In this work, we constructing type II heterojunction by in-situ coupling Zn0.3Cd0.7S quantum dots (ZCS QDs) on three-dimensionally ordered microporous CaTiO3 (3DOM CTO) for photocatalytic H2 production and glucose conversion. The DFT calculations demonstrate that substitution of Zn on the Cd site improves the separation and transmission of photogenerated carriers. Therefore, 3DOM CTO-ZCS composite exhibits best H2 production performance (2.81 mmol g-1h-1) and highest apparent quantum efficiency (AQY) (5.56 %) at 365 nm, which are about 47 and 18 times that of CTO nanoparticles (NPs). The improved catalytic performance ascribed to not only good mass diffusion and exchange, highly efficient light harvesting of 3DOM structure, but also the efficient charges separation of type Ⅱ heterojunction. The investigation on photocatalytic mechanism indicates that the glucose is mainly converted to gluconic acid and lactic acid, and the control reaction step is gluconic acid to lactic acid. The selectivity for gluconic acid on 3DOM CTO-ZCS is 85.65 %. Our work here proposes a green sustainable method to achieve highly efficient H2 production and selective conversion of glucose to gluconic acid.

Zoledronic acid and denosumab for periprosthetic bone mineral density loss after joint arthroplasty: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Periprosthetic bone mineral density (BMD) loss after total hip arthroplasty (THA) may threaten the survival of implants. Zoledronic acid (ZA) and denosumab were effective in reducing bone loss in conditions associated with accelerated bone turnover by inhibiting osteoclast activity. This meta-analysis aimed to assess the efficiency and safety of ZA and denosumab for periprosthetic BMD loss after THA. METHODS: A systematic search of randomized controlled trials (RCTs) associated with ZA or denosumab and THA was performed in MEDLINE, PubMed, Embase, the Cochrane Central Register of Controlled Trials, and the Web of Science from 1980 to 2022. Meta-analysis was performed by the Cochrane Review Manager 5 (RevMan) version 5.41. Cochrane risk of bias tool and GRADEpro were applied for methodological quality and overall evidence quality, respectively. RESULTS: Nine RCTs involving a total of 480 patients were finally included and analyzed. The pooled data that demonstrated significantly less periprosthetic BMD loss in Gruen zone 7 occurred in the intervention group patients than in the control group patients at 3 months (MD = 4.30, 95% CI: 1.78-6.82, P = 0.0008), 6 months (MD = 7.71, 95% CI: 5.41-10.02, P < 0.00001), and 12 months (MD = 8.19, 95% CI: 5.97-10.42, P < 0.00001) after THA. No serious adverse events (AEs) were observed. CONCLUSION: In the current analysis with evidence on the efficacy and safety of ZA and denosumab, the authors recommend the use of ZA or denosumab treatment for periprosthetic bone mineral density loss. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number: CRD42022369273.

Egg Rejection and Nest Sanitation in an Island Population of Barn Swallows (Hirundo rustica): Probability, Response Latency, and Sex Effects.

Bird nests function as vessels for eggs and nestlings, and an environment for rearing offspring. However, foreign objects falling into bird nests and nestling eggshells may be harmful. Moreover, the smell of fecal sacs increases the risk of detection by predators. Many bird species have evolved nest sanitation to prevent damage to their nests. Furthermore, egg rejection evolved in some birds to thwart brood parasites that lay eggs in their nests. We studied 133 nests of barn swallows (Hirundo rustica) in an island population through a nest content manipulation experiment to determine nest sanitation and egg rejection behaviors and their relationship. Swallows rejected non-egg foreign objects more frequently (100% vs. 58.6%) and sooner than parasite eggs, which supports the hypothesis that nest sanitation is a pre-adaptation to egg rejection. However, nest sanitation did not increase egg rejection, either in probability or latency. Furthermore, both sexes incubated the eggs, cleaned the nests, and removed parasite eggs, implying that both are confronted with natural selection related to nest sanitation and brood parasitism. However, females invested more time in these behaviors than males. This provides evidence for the evolutionary relationship of nest sanitation and egg rejection behaviors in barn swallows.

Change of algal organic matter under different dissolved oxygen and pressure conditions and its related disinfection by-products formation potential in metalimnetic oxygen minimum.

Most of the reservoirs or lakes will form a metalimnetic oxygen minimum (MOM) with the characterization of a substantial fraction of dissolved oxygen (DO) depleted below the epilimnion. The effect of intracellular organic matter (IOM) of algal cells transformed under MOM conditions is completely different from that of the original IOM on water quality. In this study, the IOM changes of Microcystic aeruginosa under different MOM conditions and its related disinfection by-products formation potentials (DBPFPs) were investigated by changing the pressure and DO concentration of MOM. Total Fmax increased slightly and then decreased under different pressure conditions, finally decreasing by no more than 22.0%. Under aerobic condition, dissolved organic carbon (DOC) and total Fmax decreased significantly, and decreased by 60.4% and 38.8% within the first 2 days. The results of specific UV absorbance (SUVA) and UV250/UV365 indicated that aromatic compounds and average molecular weight of IOM were gradually increased under different MOM conditions. The total DBPFPs increased firstly and then decreased under different pressure conditions, and finally decreased by 26.2%-33.1%. The decrease of total DBPFPs was significantly higher under aerobic condition than that under anoxic condition, which finally decreased by 64.5%. Redundancy analysis showed that the fluorescence parameter (protein-like and humic-like fluorescence) could be expected as an index to predict the DBPFPs. Moreover, the results revealed that with the decrease of DO, the activity and diversity of natural microbial consortium decreased, which prevented the further degradation and utilization of organic matter by natural microbial consortium. Therefore, lower DO was a key player for the deterioration of water quality under MOM conditions.

Anti-Predation Responses to Conspecific versus Heterospecific Alarm Calls by the Nestlings of Two Sympatric Birds.

Predation is generally the main cause of bird mortality. Birds can use acoustic signals to increase their predation survival. Bird response to mobbing alarm calls is a form of anti-predation behavior. We used a playback technique and acoustic analysis to study the function of mobbing alarm calls in the parent-offspring communication of two sympatric birds, the vinous throated parrotbill (Sinosuthora webbianus) and oriental reed warbler (Acrocephalus orientalis). The chicks of these two species responded to conspecific and heterospecific mobbing alarm calls by suppressing their begging behavior. The mobbing alarm calls in these two species were similar. Mobbing alarm calls play an important role in parent-offspring communication, and chicks can eavesdrop on heterospecific alarm calls to increase their own survival. Eavesdropping behavior and the similarity of alarm call acoustics suggest that the evolution of alarm calls is conservative and favors sympatric birds that have coevolved to use the same calls to reduce predation risk.

All-Inorganic Perovskite Single-Crystal Photoelectric Anisotropy.

Engineering surface structure can precisely and effectively tune the optoelectronic properties of halide perovskites, but are incredibly challenging. Herein, the design and fabrication of uniform all-inorganic CsPbBr3 cubic/tetrahedral single-crystals are reported with precise control of the (100) and (111) surface anisotropy, respectively. By combining with theoretical calculations, it is demonstrated that the preferred (100) surface engineering of the CsPbBr3 single-crystals enables a lowest surface bandgap energy (2.33 eV) and high-rate carrier mobility up to 241 µm2  V-1  s-1 , inherently boosting their light-harvesting and carrier-transport capability. Meanwhile, the polar (111) surface induces ≈0.16 eV upward surface-band bending and ultrahigh surface defect density of 1.49 × 1015  cm-3 , which is beneficial for enhancing surface-defects-catalyzed reactions. The work highlights the anisotropic surface engineering for boosting perovskite optoelectronic devices and beyond.

TFAM downregulation promotes autophagy and ESCC survival through mtDNA stress-mediated STING pathway.

The dynamics of mitochondrial biogenesis regulation is critical in maintaining cellular homeostasis for immune regulation and tumor prevention. Here, we report that mitochondrial biogenesis disruption through TFAM reduction significantly impairs mitochondrial function, induces autophagy, and promotes esophageal squamous cell carcinoma (ESCC) growth. We found that TFAM protein reduction promotes mitochondrial DNA (mtDNA) release into the cytosol, induces cytosolic mtDNA stress, subsequently activates the cGAS-STING signaling pathway, thereby stimulating autophagy and ESCC growth. STING depletion or mtDNA degradation by DNase I abrogates mtDNA stress response, attenuates autophagy, and decreases the growth of TFAM depleted cells. In addition, autophagy inhibitor also ameliorates mitochondrial dysfunction-induced activation of the cGAS-STING signaling pathway and ESCC growth. In conclusion, our results indicate that mtDNA stress induced by mitochondria biogenesis perturbation activates the cGAS-STING pathway and autophagy to promote ESCC growth, revealing an underappreciated therapeutic strategy for ESCC.

A dataset of bird distributions in zoogeographical regions of China.

Background: China, the largest country in Asia, has a land area of approximately 9.6 million square kilometres. There are 1481 bird species (following the taxonomy of IOC World Bird List version 12.1) recorded in two zoogeographical realms, seven regions and 19 subregions in the country. From 1955 to 2017, six authoritative monographs were published, which recorded the distribution area for all bird species in China and were widely quoted by research papers and field guides. This massive amount of data could be used to address many hot topics in ornithology, biogeography and ecology. However, rapid changes in the taxonomic status and different schemes of zoogeographical regionalisation in these six monographs provided limits to the utilisation of these valuable data. New information: By integrating the data from the six monographs, we presented an open-access dataset on the occurrences and residence types of all Chinese bird species in zoogeographical regions over the past 60 years. The taxonomic statuses for these species were determined following the IOC World Bird List version 12.1 and the zoogeographical regions were based on the updated scheme. These data provide valuable information for the research in bird ecology and conservation biology.

Parent-offspring and inter-offspring responses to conspecific versus heterospecific distress calls in 2 sympatric birds.

Distress calls, as a type of alarm call, play important roles in expressing bodily condition and conveying information concerning predation threats. In this study, we examined the communication via distress calls in parent-offspring and inter-offspring interactions. First, we used playback of chick distress calls of 2 sympatric breeders, the vinous-throated parrotbill Sinosuthora webbiana and the oriental reed warbler Acrocephalus orientalis, to the adults/chicks of these 2 species, respectively, and measured the responses of conspecifics or heterospecifics. The playback-to-chicks experiment showed that both species of chicks reduced the number of begging calls and begging duration time as a response to conspecific/heterospecific distress calls compared with natural begging and background noise controls. However, reed warbler chicks also reduced beak opening frequency in the response to conspecific distress calls compared with other playback stimuli. Second, the results of the playback-to-adults experiment showed that reed warbler adults could eavesdrop on distress calls of conspecific neighbors and sympatric heterospecifics. Furthermore, the nest-leaving behavior of reed warblers did not differ significantly when they heard the distress calls of conspecifics or parrotbills. Finally, reed warbler adults responded to heterospecific distress calls more quickly than to conspecific distress calls, and parrotbill adults presented the same response. Our results supported the warn-kin hypothesis and show that chick distress calls play an important role in conveying risk and the condition of chicks to enhance individual fitness. In addition, we also found that eavesdropping on distress calls is a congenital behavior that begins in the chick stage.

Ivermectin induces apoptosis of esophageal squamous cell carcinoma via mitochondrial pathway.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents. METHODS: The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels. RESULTS: Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, we found that ivermectin markedly mediated mitochondrial dysfunction and induced apoptosis of ESCC cells, which indicated the anti-proliferative effect of ivermectin on ESCC cells was implicated in mitochondrial apoptotic pathway. Mechanistically, ivermectin significantly triggered ROS accumulation and inhibited the activation of NF-κB signaling pathway and increased the ratio of Bax/Bcl-2. CONCLUSIONS: These finding indicated that ivermectin has significant anti-tumour potential for ESSC and may be a potential therapeutic candidate against ESCC.

Distribution characteristics and noncarcinogenic risk assessment of culturable airborne bacteria and fungi during winter in Xinxiang, China.

Bioaerosols are an important component of particulate matter in the atmosphere and are harmful to human health. In this study, the concentration, size distribution, and factors influencing culturable airborne bacteria and fungi in the atmosphere were investigated using a six-stage impactor device in the city of Xinxiang, China, during the winter season. The results revealed that the concentration of culturable airborne bacteria and fungi varied significantly during the sampling period: 4595 ± 3410 and 6358 ± 5032 CFU/m3, respectively. The particle sizes of the bioaerosols were mainly within stage V (1.1-2.1 µm), and fine particulate matter accounted for 45.9% ± 18.9% of airborne bacteria and 52.0% ± 18.5% of airborne fungi, respectively. With the deterioration of air quality, the concentration of airborne fungi gradually increased, and that of airborne bacteria increased when the air quality index was lower than 200 and decreased when it was higher than 200. With respect to the diurnal variation pattern of bioaerosol concentration, the highest and lowest concentrations were registered at night and noon, respectively, probably because of changes in ultraviolet radiation intensity. Bioaerosol concentration positively correlated with humidity, concentration of PM2.5, PM10, SO2, and NO2 and negatively correlated with O3 concentration. The risk of exposure of humans to the airborne bacteria was primarily associated with the respiratory inhalation pathway, and the risk of skin exposure was negligible. These results should improve our understanding of the threat of bioaerosols to public health.