The comparison of white-to-white via triple person-times caliper measuring and machine-measuring in V4c implantable collamer lens implantation.

This study aimed to compare the differences and characteristics of white-to-white (WTW) values obtained before V4c implantation using triple person-times caliper, IOL-Master 700, Pentacam HR, and UBM, and to assess their correlation with vaulting. A total of 930 myopia patients (1842 eyes) who were interested in undergoing ICL surgery were assessed before the procedure using various instruments. The WTW measurements were obtained using a triple person-times caliper, Pentacam HR, and IOL-Master 700, whereas the angle-to-angle (ATA) measurements were obtained using UBM. The size of the ICL was subsequently calculated using triple person-times caliper measurements. The vault of the ICL was assessed using Pentacam HR three months after the surgery. The WTW was determined to be 11.30 ± 0.29 mm, 11.43 ± 0.29 mm, and11.86 ± 0.38 mm, respectively, using the triple person-times caliper, Pentacam HR, and IOL-Master 700. The measurement of ATA was 11.57 ± 0.51 mm, as done by UBM. The ICL vault was measured to be 400.97 ± 198.46 µm when examined with Pentacam HR three monthsafter the procedure. The linear regression analyses of ICL size and WTW of triple person-times caliper, ICL vault and WTW were (R = 0.703, p < 0.001; R = 0.0969, p < 0.001) respectively. The highest correlation was found between IOL-Master and Pentacam HR (r = 0.766, p = 0.000). The lowest correlation was found between UBM and Pentacam HR (r = 0.358, p = 0.002). Bland-Altman analysis showed that the 95% limits of agreement (LoA) were the triple person-times caliper and Pentacam HR (- 0.573, 0.298) and the triple person-times caliper and UBM (- 1.15, - 0.605). This indicated a strong agreement between the triple person-times caliper and Pentacam HR and a lack of agreement between the triple person-times caliper and UBM. Triple person-times caliper measurements offer excellent maneuverability, practicality, and reliable outcomes for determining ICL vaults. Measurements obtained using the triple-person caliper were less differece than those obtained using the Pentacam HR.

Emodin alleviates intestinal ischemia/reperfusion-induced lung injury by upregulating HO-1 expression via PI3K/AkT pathway.

BACKGROUND: Emodin, a natural anthraquinone derivative found in various Chinese medicinal herbs, has been proved to be an effective therapeutic agent in the treatment of many diseases. However, its effect on lung injury after intestinal ischemia/reperfusion injury remains unknown. This research was designed to investigate whether emodin protects against intestinal ischemia/reperfusion-induced lung injury and to elucidate the underlying molecular mechanisms in vivo and in vitro. METHODS: Intestinal ischemia/reperfusion injury was induced by occluding the superior mesenteric artery in mice, and mouse lung epithelial-12 cells were subjected to oxygen-glucose deprivation and reoxygenation to establish an in vitro model. RESULTS: Our data indicated that emodin treatment reduced intestinal ischemia/reperfusion-induced oxidative stress, inflammation and apoptosis in lung tissues and alleviated lung injury. However, the protective effects of emodin on intestinal ischemia/reperfusion-induced lung injury were reversed by the protein kinase B inhibitor triciribine or the heme oxygenase-1 inhibitor tin protoporphyrin IX. The protein kinase inhibitor triciribine also downregulated the expression of heme oxygenase-1. CONCLUSION: In conclusion, our data suggest that emodin treatment protects against intestinal ischemia/reperfusion-induced lung injury by enhancing heme oxygenase-1 expression via activation of the PI3K/protein kinase pathway. Emodin may act as a potential therapeutic agent for the prevention and treatment of lung injury induced by intestinal ischemia/reperfusion.

Comparison of the cachexia index based on hand-grip strength (H-CXI) with the original CXI for the prediction of cancer cachexia and prognosis in patients who underwent radical colectomy for colorectal cancer.

Background and aims: The cachexia index (CXI) is a novel biomarker for estimating cancer cachexia. The cachexia index based on hand-grip strength (H-CXI) has been recently developed as a simple proxy for CXI. The present study aims to compare both the H-CXI and CXI for the prediction of cancer cachexia and postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. Methods: Patients who underwent radical operations for colorectal cancer were included in this study. Cancer cachexia was diagnosed according to the international consensus outlined by Fearon et al. The cachexia index (CXI) was calculated as [skeletal muscle index (SMI) × serum albumin/neutrophil-to-lymphocyte ratio (NLR)]. The H-CXI was calculated as [hand-grip strength (HGS)/height2 × serum albumin/NLR]. The SMI was measured based on the preoperative CT images at the third lumbar vertebra (L3) level. HGS was measured before surgery. Results: From July 2014 to May 2021, a total of 1,411 patients were included in the present study, of whom 361 (25.6%) were identified as having cancer cachexia. Patients with cachexia had a lower CXI (p < 0.001) and lower H-CXI (p < 0.001) than those without cachexia. A low CXI but not low H-CXI independently predicted cancer cachexia in the multivariate analysis (OR 1.448, p = 0.024). Both a low CXI (HR 1.476, p < 0.001 for OS; HR 1.611, p < 0.001 for DFS) and low H-CXI (HR 1.369, p = 0.007 for OS; HR 1.642, p < 0.001 for DFS) were independent predictors for overall survival (OS) and disease-free survival (DFS) after adjusting for the same covariates. A low H-CXI but not low CXI was an independent risk factor for postoperative complications (OR 1.337, p = 0.044). No significant association was found between cancer cachexia and postoperative complications. Conclusion: The CXI and H-CXI exhibited better prognostic value than cancer cachexia for the prediction of postoperative outcomes in patients who underwent radical colectomy for colorectal cancer. The H-CXI was a superior index over the CXI in predicting short-term clinical outcomes, whereas the CXI demonstrated a closer correlation with Fearon's criteria for cancer cachexia. Ideal tools for the assessment of cancer cachexia should incorporate not only weight loss but also muscle mass, physical function, and inflammatory state.

Prognostic value of GLIM-defined malnutrition in combination with hand-grip strength or gait speed for the prediction of postoperative outcomes in gastric cancer patients with cachexia.

BACKGROUND: Cancer cachexia is associated with impaired functional and nutritional status and worse clinical outcomes. Global Leadership Initiative in Malnutrition (GLIM) consensus recommended the application of GLIM criteria to diagnose malnutrition in patients with cachexia. However, few previous study has applied the GLIM criteria in patients with cancer cachexia. METHODS: From July 2014 to May 2019, patients who were diagnosed with cancer cachexia and underwent radical gastrectomy for gastric cancer were included in this study. Malnutrition was diagnosed using the GLIM criteria. Skeletal muscle index was measured using abdominal computed tomography (CT) images at the third lumbar vertebra (L3) level. Hand-grip strength and 6-meters gait speed were measured before surgery. RESULTS: A total of 356 patients with cancer cachexia were included in the present study, in which 269 (75.56%) were identified as having malnutrition based on the GLIM criteria. GLIM-defined malnutrition alone did not show significant association with short-term postoperative outcomes, including complications, costs or length of postoperative hospital stays. The combination of low hand-grip strength or low gait speed with GLIM-defined malnutrition led to a significant predictive value for these outcomes. Moreover, low hand-grip strength plus GLIM-defined malnutrition was independently associated with postoperative complications (OR 1.912, 95% CI 1.151-3.178, P = 0.012). GLIM-defined malnutrition was an independent predictive factor for worse OS (HR 2.310, 95% CI 1.421-3.754, P = 0.001) and DFS (HR 1.815, 95% CI 1.186-2.779, P = 0.006) after surgery. The addition of low hand-grip strength or low gait speed to GLIM-defined malnutrition did not increase its predictive value for survival. CONCLUSION: GLIM-defined malnutrition predicted worse long-term survival in gastric cancer patients with cachexia. Gait speed and hand-grip strength added prognostic value to GLIM-defined malnutrition for the prediction of short-term postoperative outcomes, which could be incorporated into preoperative assessment protocols in patients with cancer cachexia.

Decoding the complexity of on-target integration: characterizing DNA insertions at the CRISPR-Cas9 targeted locus using nanopore sequencing.

BACKGROUND: CRISPR-Cas9 technology has advanced in vivo gene therapy for disorders like hemophilia A, notably through the successful targeted incorporation of the F8 gene into the Alb locus in hepatocytes, effectively curing this disorder in mice. However, thoroughly evaluating the safety and specificity of this therapy is essential. Our study introduces a novel methodology to analyze complex insertion sequences at the on-target edited locus, utilizing barcoded long-range PCR, CRISPR RNP-mediated deletion of unedited alleles, magnetic bead-based long amplicon enrichment, and nanopore sequencing. RESULTS: We identified the expected F8 insertions and various fragment combinations resulting from the in vivo linearization of the double-cut plasmid donor. Notably, our research is the first to document insertions exceeding ten kbp. We also found that a small proportion of these insertions were derived from sources other than donor plasmids, including Cas9-sgRNA plasmids, genomic DNA fragments, and LINE-1 elements. CONCLUSIONS: Our study presents a robust method for analyzing the complexity of on-target editing, particularly for in vivo long insertions, where donor template integration can be challenging. This work offers a new tool for quality control in gene editing outcomes and underscores the importance of detailed characterization of edited genomic sequences. Our findings have significant implications for enhancing the safety and effectiveness of CRISPR-Cas9 gene therapy in treating various disorders, including hemophilia A.

The comparison of corneal higher-order aberration and surgically induced astigmatism between the clear corneal incision and the limbus tunnel incision of posterior chamber implantable collamer lens implantation.

BACKGROUND: This study aimed to compare the corneal high-order aberrations and surgically induced astigmatism between the clear corneal incision and limbus tunnel incision for posterior chamber implantable collamer lens (ICL/TICL) implantation. METHODS: A total of 127 eyes from 73 myopic patients underwent ICL V4c implantation, with 70 eyes receiving clear corneal incisions and 57 eyes receiving limbus tunnel incisions. The anterior and back corneal surfaces were measured and the Root Mean Square of all activated aberrations (TRMS) was calculated, including higher-order aberration (HOA RMS), spherical aberration Z40, coma coefficients (Coma RMS) Z3-1 Z31, and surgically induced astigmatism (SIA). The measurements were taken preoperatively and postoperatively at 1 day, 1 week, and 1, 3, and 6 months. In this study, the corneal higher-order aberration was estimated as the Zernike coefficient calculated up to 5th order. The measurements were taken at a maximum diameter of 6.5 mm using Pentacam. RESULTS: One week after the operation, the corneal back Z31 of the clear corneal incision group was 0.06 ± 0.06, while the limbus tunnel incision group showed a measurement of 0.05 ± 0.06 (p = 0.031). The corneal back Z40 of the clear corneal incision group was -0.02 ± 0.25, compared to -0.04 ± 0.21 in the limbus tunnel incision group (p = 0.01). One month after the operation, the corneal back SIA of the clear corneal incision group was 0.11 ± 0.11, compared to 0.08 ± 0.11of the limbus tunnel incision group (p = 0.013), the corneal total SIA of the clear corneal incision group was 0.33 ± 0.30, compared to 0.15 ± 0.16 in the limbus tunnel incision group (p = 0.004); the clear corneal incision group exhibited higher levels of back astigmatism and total SIA than the limbus tunnel incision in the post-operation one month period. During the 6- month post-operative follow-up period, no significant difference in Z31, Z40, and other HOA RMS data was observed between the two groups. The total SIA of the corneal incision group and the limbus tunnel incision group were 0.24 ± 0.14 and 0.33 ± 0.32, respectively (p = 0.393), showing no significant difference between the two groups 6 months after the operation. CONCLUSION: Our data showed no significant difference in the high-order aberration and SIA between clear corneal incision and limbus tunnel incision up to 6 months after ICL-V4c implantation.

Sarcopenia predicts postoperative complications and survival in colorectal cancer patients with GLIM-defined malnutrition: Analysis from a prospective cohort study.

OBJECTIVE: To investigate whether sarcopenia could predict postoperative outcomes in patients with colorectal cancer with Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition. METHODS: Clinical data of patients who underwent radical resection for colorectal cancer were prospectively collected. Sarcopenia was diagnosed by the combination of low handgrip strength and low muscle quantity or quality as measured by abdominal computed tomography (CT) images. Logistic regression analysis and Cox proportional hazards regression analysis were performed to identify independent predictors for postoperative complications and survival, respectively. RESULTS: A total of 310 patients with colorectal cancer with GLIM-defined malnutrition were included, of which 145 (46.77%) were identified with sarcopenia. Malnutritional patients with sarcopenia had significantly higher incidences of total complications (34.5% versus 15.8%), severe complications (9.7% versus 1.8%), longer lengths of postoperative hospital stay (median, 14 days versus 12 days), and more costs (median, 56,257 RMB versus 49,024 RMB) than those without sarcopenia. Sarcopenia was an independent predictive factor for postoperative complications (OR 2.531, 95% CI 1.451-4.415), overall survival (HR 1.519, 95% CI 1.026-2.248), and disease-free survival (HR 1.847, 95% CI 1.324-2.576). Patients with severe sarcopenia had a higher incidence of severe complications but not total complications or survival than those with not-severe sarcopenia. Moreover, the predictive value of sarcopenia for postoperative complications was attributed to muscle strength and quality but not muscle quantity. CONCLUSION: Sarcopenia predicts postoperative complications and survival in patients with colorectal cancer with GLIM-defined malnutrition. Preoperative assessment of sarcopenia is still necessary when nutritional assessment has been well performed.

Fibroblast growth factor 5 protects against spinal cord injury through activating AMPK pathway.

Excessive productions of inflammatory cytokines and free radicals are involved in spinal cord injury (SCI). Fibroblast growth factor 5 (FGF5) is associated with inflammatory response and oxidative damage, and we herein intend to determine its function in SCI. Lentivirus was instilled to overexpress or knockdown FGF5 expression in mice. Compound C or H89 2HCl were used to suppress AMP-activated protein kinase (AMPK) or protein kinase A (PKA), respectively. FGF5 level was significantly decreased during SCI. FGF5 overexpression mitigated, while FGF5 silence further facilitated inflammatory response, oxidative damage and SCI. Mechanically, FGF5 activated AMPK to attenuate SCI in a cAMP/PKA-dependent manner, while inhibiting AMPK or PKA with pharmacological methods significantly abolished the neuroprotective effects of FGF5 against SCI. More importantly, serum FGF5 level was decreased in SCI patients, and elevated serum FGF5 level often indicate better prognosis. Our study identifies FGF5 as an effective therapeutic and prognostic target for SCI.

Rheological Role of Stiff Nanorings on Concurrently Strengthening and Toughening Polymer Nanocomposites.

Nanorings, which are increasingly uncovered in natural systems and synthesized in man-made materials, exhibit dynamics distinct from those known for linear chains. We show in this study that, when immersed in a polymer melt matrix, segments of a stiff nanoring (SNR) have more facilitated subdiffusion, i.e., with a larger scaling exponent in the mean squared displacement, than those belonging to one flexible counterpart, while the whole SNR is more suppressed by its surroundings. It is revealed that adding SNRs contributes to achieving the long-anticipated rheological objective of sol- and gel-like characteristics at high and low shearing frequencies, respectively. This study suggests the promising prospect of exploiting SNRs to concurrently strengthen and toughen target polymer nanocomposites.

ß-Carboline Alkaloids From the Deep-Sea Fungus Trichoderma sp. MCCC 3A01244 as a New Type of Anti-pulmonary Fibrosis Agent That Inhibits TGF-ß/Smad Signaling Pathway.

Pulmonary fibrosis is a scarring disease of lung tissue, which seriously threatens human health. Treatment options are currently limited, and effective strategies are still lacking. In the present study, 25 compounds were isolated from the deep-sea fungus Trichoderma sp. MCCC 3A01244. Among them, two ß-carboline alkaloids, trichocarbolines A (1) and C (4) are new compounds. The chemical structures of these compounds were elucidated based on their HRESIMS, 1D and 2D NMR spectra, optical rotation calculation, and comparisons with data reported in the literature. Trichocarboline B [(+)- and (-)-enantiomers] had previously been synthesized, and this is its first report as a natural product. Their anti-pulmonary fibrosis (PF) activity and cytotoxicity were investigated. Compounds 1, 11, and 13 strongly inhibited TGF-ß1-induced total collagen accumulation and showed low cytotoxicity against the HFL1 cell line. Further studies revealed compound 1 inhibited extracellular matrix (ECM) deposition by downregulating the expression of protein fibronectin (FN), proliferating cell nuclear antigen (PCNA), and α-smooth muscle actin (α-SMA). Mechanistic study revealed that compound 1 decreased pulmonary fibrosis by inhibiting the TGF-ß/Smad signaling pathway. As a newly identified ß-carboline alkaloid, compound 1 may be used as a lead compound for developing more efficient anti-pulmonary fibrosis agents.

Exophilone, a Tetrahydrocarbazol-1-one Analogue with Anti-Pulmonary Fibrosis Activity from the Deep-Sea Fungus Exophiala oligosperma MCCC 3A01264.

A new compound, exophilone (1), together with nine known compounds (2-10), were isolated from a deep-sea-derived fungus, Exophiala oligosperma. Their chemical structures, including the absolute configuration of 1, were elucidated using nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectroscopy (HRESIMS), and electronic circular dichroism (ECD) calculation. Compounds were preliminarily screened for their ability to inhibit collagen accumulation. Compounds 1, 4, and 7 showed weaker inhibition of TGF-ß1-induced total collagen accumulation in compared with pirfenidone (73.14% inhibition rate). However, pirfenidone exhibited cytotoxicity (77.57% survival rate), while compounds 1, 4, and 7 showed low cytotoxicity against the HFL1 cell line. Particularly, exophilone (1) showed moderate collagen deposition inhibition effect (60.44% inhibition rate) and low toxicity in HFL1 cells (98.14% survival rate) at a concentration of 10 µM. A molecular docking study suggests that exophilone (1) binds to both TGF-ß1 and its receptor through hydrogen bonding interactions. Thus, exophilone (1) was identified as a promising anti-pulmonary fibrosis agent. It has the potential to be developed as a drug candidate for pulmonary fibrosis.

Facile construction of core-shell Carbon@CoNiO2 derived from yeast for broadband and high-efficiency microwave absorption.

Manufacturing dielectric/magnetic composites with hierarchical structure is regard as a promising strategy for the progress of high-performance microwave absorption (MA) materials. In this paper, the nano-grass structured CoNiO2 magnetic shell was uniformly anchored on the yeast-derived carbon microspheres by in-situ one-pot synthesis method. Profiting from the unique nano-grass and core-shell structure, capable dielectric/magnetic loss, along with improved impedance matching, the prepared absorber realizes desirable MA performance. The minimum reflection loss (RLmin) reaches up to -44.06 dB at 6.56 GHz. Moreover, the effective absorption bandwidth (EAB, reflection loss (RL) < -10 dB) accomplishes 7.04 GHz under a low filler loading of 20 wt%. This work endeavors a valuable insight for designing innovative core-shell structured materials with high-efficiency MA and broad bandwidth.

Delayed diffuse lamellar keratitis after small-incision lenticule extraction related to immunoglobulin A nephropathy: A case report.

BACKGROUND: Diffuse lamellar keratitis (DLK) is a complication of laser-assisted in situ keratomileusis (LASIK). This condition can also develop after small-incision lenticule extraction (SMILE) with a distinctive appearance. We report the case involving a female patient with delayed onset DLK accompanied by immunoglobulin A (IgA) nephropathy. CASE SUMMARY: A 22-year-old woman was referred to our department for DLK and a decline in vision 1 mo after undergoing SMILE. The initial examination showed grade 2 DLK in the flap involving the central visual axis of the right eye. She was immediately administered with a large dose of a topical steroid for 30 d. However, the treatment was ineffective. Her vision deteriorated from 10/20 to 6/20, and DLK gradually worsened from grade 2 to 4. Eventually, interface washout was performed, after which her vision improved. DLK completely disappeared 2 mo after washout. Six months after SMILE, the patient was diagnosed with IgA nephropathy due to a 4-year history of interstitial hematuria. CONCLUSION: DLK is a typical complication of LASIK but can also develop after SMILE. Topical steroid therapy was ineffective in our patient, and interface washout was required. IgA nephropathy could be one of the factors contributing to the development of delayed DLK after SMILE.

Serpentine-Inspired Strain Sensor with Predictable Cracks for Remote Bio-Mechanical Signal Monitoring.

Flexible strain sensors have attracted intense interest due to their application as intelligent wearable electronic devices. However, it is still a huge challenge to achieve a flexible sensor with simultaneous high sensitivity, excellent durability, and a wide sensing region. In this work, a crack-based strain sensor with a paired-serpentine conductive network is fabricated onto flexible film by screen printing. The innovative conductive network exhibits a controlled crack morphology during stretching, which endows the prepared sensor with outstanding sensing characteristics, including high sensitivity (gauge factor up to 2391.5), wide detection (rang up to 132%), low strain detection limit, a fast response time (about 40 ms), as well as excellent durability (more than 2000 stretching/releasing cycles). Benefiting from these excellent performances, full-range human body motions including subtle physiological signals and large motions are accurately detected by the prepared sensor. Furthermore, wearable electronic equipment integrated with a wireless transmitter and the prepared strain sensor shows great potential for remote motion monitoring and intelligent mobile diagnosis for humans. This work provides an effective strategy for the fabrication of novel strain sensors with highly comprehensive performance.

MicroRNA-299a-5p Protects against Spinal Cord Injury through Activating AMPK Pathway.

Objective: Inflammation and oxidative stress are implicated in the pathogenesis of spinal cord injury (SCI). The present study is aimed at investigating the function and molecular basis of microRNA-299a-5p (miR-299a-5p) during SCI in mice. Methods: Mice were exposed to SCI surgery and then intrathecally injected with the agomir, antagomir, or matched negative controls of miR-299a-5p to overexpress or silence miR-299a-5p. To inhibit AMP-activated protein kinase (AMPK), mice were intraperitoneally injected with compound C (CC). To overexpress pH domain and leucine-rich repeat protein phosphatase 1 (PHLPP1), lentiviral vectors were used. Results: The miR-299a-5p expression in the spinal cord was dramatically reduced by SCI stimulation. The miR-299a-5p agomir prevents, while the miR-299a-5p antagomir exacerbates inflammation, oxidative stress, and SCI in mice. Mechanistically, we found that miR-299a-5p directly inhibited PHLPP1 and subsequently activated AMPK pathway. The PHLPP1 overexpression of AMPK inhibition with either genetic or pharmacologic methods dramatically abolished the miR-299a-5p agomir-mediated protective effects against SCI. Conclusion: miR-299a-5p protects against spinal cord injury through activating AMPK pathway.

Three-dimensional macroporous hybrid carbon aerogel with heterogeneous structure derived from MXene/cellulose aerogel for absorption-dominant electromagnetic interference shielding and excellent thermal insulation performance.

The development of electromagnetic interference (EMI) shielding materials with excellent absorption coefficient (A) is vital to completely eliminate the pollution of the ever-increasing electromagnetic waves (EMWs). In this regard, a TiC/carbon hybrid aerogel, derived from MXene/cellulose aerogel, was successfully fabricated via freeze-drying and subsequent pyrolysis process. Profiting from the open, loose three-dimensional (3D) macro pores with sheet-like morphology and high porosity, as well as the rich heterogeneous interfaces between TiC and cellulose-derived carbon, the as-prepared hybrid carbon aerogel achieves ultra-efficient EMI shielding effectiveness of 72.9 dB in conjunction with a superior A value of 0.76 and low thermal conductivity. These properties endow the as-prepared aerogel with strong absorption-dominant ultra-efficient EMI shielding and thermal insulation performance to meet the complex practical requirements. This work provides a promising strategy for achieving ultra-efficient multifunctional EMI shielding performance and superior A simultaneously.

Metabolic tuning of a stable microbial community in the surface oligotrophic Indian Ocean revealed by integrated meta-omics.

Understanding the mechanisms, structuring microbial communities in oligotrophic ocean surface waters remains a major ecological endeavor. Functional redundancy and metabolic tuning are two mechanisms that have been proposed to shape microbial response to environmental forcing. However, little is known about their roles in the oligotrophic surface ocean due to less integrative characterization of community taxonomy and function. Here, we applied an integrated meta-omics-based approach, from genes to proteins, to investigate the microbial community of the oligotrophic northern Indian Ocean. Insignificant spatial variabilities of both genomic and proteomic compositions indicated a stable microbial community that was dominated by Prochlorococcus, Synechococcus, and SAR11. However, fine tuning of some metabolic functions that are mainly driven by salinity and temperature was observed. Intriguingly, a tuning divergence occurred between metabolic potential and activity in response to different environmental perturbations. Our results indicate that metabolic tuning is an important mechanism for sustaining the stability of microbial communities in oligotrophic oceans. In addition, integrated meta-omics provides a powerful tool to comprehensively understand microbial behavior and function in the ocean. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-021-00119-6.

To explore the active constituents of Sedum aizoon L in the treatment of coronary heart disease based on network pharmacology and molecular docking methodology.

Background: There is a lack of effective drugs for the treatment of coronary heart disease (CHD). Sedum aizoon L (SL) has multiple effects, and there is no report on CHD in SL at present. The aim of this study is to explore the mechanisms of action of SL in the treatment of CHD based on network pharmacology and molecular docking technology. Methods: The targets and active ingredients of SL were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and CHD-related targets were obtained by searching GeneCards and DisGeNet databases. The intersection of LS active ingredient targets and CHD targets was used to construct a "drug-ingredient-disease-target" network using the Cytoscape software. The STRING database was used to construct a protein-protein interaction (PPI) network, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Key targets and core active ingredients were selected and molecular docking was performed using the AutoDock software. Results: According to the predicted results, a total of 134 corresponding target genes for LS, 12 active components, 1,704 CHD-related targets, and 52 intersecting targets were obtained. GO function and KEGG pathway analysis showed that the key targets were involved with signal transducer and activator of transcription 3 (STAT3), tumor protein p53 (TP53), and vascular endothelial growth factor A (VEGFA). The molecular docking results showed that the key targets bound to the important active ingredients in a stable conformation. The core active ingredients of LS in the treatment of CHD were determined to be ursolic acid, myricetin, and beta-sitosterol. Conclusions: SL may act on targets such as STAT3, TP53, and VEGFA through tumor necrosis factor (TNF) signaling pathway, interleukin 17A (IL-17A) signaling pathway, AGE-RAGE signaling pathway in diabetic complications, and other related pathways, thereby playing a role in preventing and treating CHD.

Chemical Constituents of the Deep-Sea-Derived Penicillium solitum.

A systematic chemical investigation of the deep-sea-derived fungus Penicillium solitum MCCC 3A00215 resulted in the isolation of one novel polyketide (1), two new alkaloids (2 and 3), and 22 known (4-25) compounds. The structures of the new compounds were established mainly on the basis of exhaustive analysis of 1D and 2D NMR data. Viridicatol (13) displayed moderate anti-tumor activities against PANC-1, Hela, and A549 cells with IC50 values of around 20 µM. Moreover, 13 displayed potent in vitro anti-food allergic activity with an IC50 value of 13 µM, compared to that of 92 µM for the positive control, loratadine, while indole-3-acetic acid methyl ester (9) and penicopeptide A (10) showed moderate effects (IC50 = 50 and 58 µM, respectively).

Intraoperative radiotherapy vs concurrent chemoradiotherapy in the treatment of patients with locally advanced pancreatic cancer.

PURPOSE: The purpose of the multi-institutional retrospective study was to evaluate whether intraoperative radiotherapy (IORT) has advantages in the treatment of patients with locally advanced pancreatic cancer (LAPC) compared with concurrent chemoradiotherapy (CCRT). PATIENTS AND METHODS: A total of 103 patients with LAPC whom was treated with IORT (Arm A; n = 50) or CCRT (Arm B; n = 53) from 2015.6 to 2016.7 were retrospectively identified. Data on feasibility, toxicity, and overall survival (OS) were evaluated. RESULTS: Most factors of the two cohorts were similar. The severe adverse events (grade 3 and 4) patients in Arm B were higher than patients in Arm A (34% vs 0%). Disease progression was noted in 38 patients (76%) in Arm A and 37 patients (69.8%) in Arm B. The median survival of patients in Arm A and B were 15.3 months (95% CI, 13.0-17.6 months) and 13.8 months (95% CI, 11.0-16.6 months), respectively. The 1-year survival rate were 66.3% in Arm A (95% CI, 52.3%-80.2%) and 60.9% in Arm B (95% CI, 46.4%-75.4%). There was no significant difference in OS between patients treated with IORT and with CCRT (p = 0.458). CONCLUSION: Our results demonstrated that patients with LAPC treated with IORT showed fewer adverse events, less treatment time, and high feasibility compared to CCRT. Although, IORT has no advantages in survival and tumor control compared with CCRT.