Analysis of Associated Factors, Construction, and Application of a Predictive Model for Lymph Node Metastasis in Colorectal Cancer.

Background: In colorectal cancer (CRC) , understanding lymph node metastasis (LNM) is critical for effective treatment. Better approaches are required for identifying and assessing the risk contributions of factors influencing lymph node metastasis in colorectal cancer. Objective: This study aims to analyze factors associated with LNM in CRC and develop a risk prediction model. Methods: A retrospective cohort study was conducted and a total of 181 CRC patients admitted between March 2020 and April 2023 were selected as research participants. Among them, 47 patients developed LNM, while the remaining 134 did not. Clinical data, including age, sex, pathological stages, were collected. Logistic regression was employed to identify factors influencing LNM in CRC, forming the basis for constructing a risk model. The diagnostic efficiency of this model was assessed through receiver operating characteristic (ROC) curves. Results: Tumor nodules and histological types showed no correlation with LNM in CRC (P > .05). However, pathological staging, vascular and neural invasion, use of VEGF inhibitors, and preoperative CEA were identified as independent risk factors for LNM in CRC (P < .05). The established model demonstrated a good fit with the observations. ROC curve analysis indicated an area under the curve (AUC) of 0.884 for predicting LNM in CRC, signifying excellent predictive performance. Conclusions: The risk model, formulated on factors associated with LNM in CRC, serves as a efficient tool in assessing the probability of LNM. It provides invaluable insights that can significantly enhance clinical approaches to the diagnosis and treatment of CRC in the future.

A novel CD8+ T cell-related gene signature as a prognostic biomarker in hepatocellular carcinoma.

CD8+ T cells have great roles in tumor suppression and elimination of various tumors including hepatocellular carcinoma (HCC). Nonetheless, potential prognostic roles of CD8+ T cell-related genes (CD8Gs) in HCC remains unknown. In our study, 416 CD8Gs were identified in HCC, which were enriched in inflammatory and immune signaling pathways. Using The Cancer Genome Atlas dataset, a 5-CD8Gs risk model (KLRB1, FYN, IL2RG, FCER1G, and DGKZ) was constructed, which was verified in International Cancer Genome Consortium and gene expression omnibus datasets. Furthermore, we found that overall survival was independently correlated with the CD8Gs signature, and it was associated with immune- and cancer-related signaling pathways and immune cells infiltration. Finally, drug sensitivity data indicated that 10 chemotherapeutic drugs held promise as therapeutics for HCC patients with high-risk. In conclusion, multi-databases analysis showed that 5-CD8Gs and their signature could be an indicator to predict candidate drugs for HCC therapy.

Rational Combination of π-Conjugated and Non-π-Conjugated Groups Achieving Strong Nonlinear Optical Response, Large Optical Anisotropy, and UV Light-Switchable Fluorescence.

Combining π-conjugated and non-π-conjugated groups is an important strategy for synthesizing new nonlinear optical (NLO) crystals. However, the second harmonic generation (SHG) response and optical anisotropy can be limited by improper spatial alignment of these functional groups in the crystal structure. In this work, it is revealed that non-π-conjugated [NH2 SO3 ] group acts as both hydrogen bond donor and acceptor, effectively regulating the 2D planar structure formed by π-conjugated [C4 N3 H6 ] groups. The resulting organic-inorganic hybrid crystal C4 N3 H6 SO3 NH2 exhibits a strong SHG response (2.5 × KDP), large optical anisotropy (0.233@546 nm), and blue-violet and green fluorescence near 360 and 520 nm, respectively. This work expands the methodology for creating new NLO crystals through organic-inorganic hybridization, while also showcasing the potential of C4 N3 H6 SO3 NH2 as a multifunctional optical material.

Eu3+ -Directed Supramolecular Metallogels with Reversible Quadruple-Stimuli Response Behaviors.

Smart luminescent materials that have the ability to reversibly adapt to external environmental stimuli and possess a wide range of responses are continually emerging, which place higher demands on the means of regulation and response sites. Here, europium ions (Eu3+ )-directed supramolecular metallogels are constructed by orthogonal self-assembly of Eu3+ based coordination interactions and hydrogen bonding. A new organic ligand (L) is synthesized, consisting of crown ethers and two flexible amide bonds-linked 1,10-phenanthroline moieties to coordinate with Eu3+ . Synergistic intermolecular hydrogen bonding in L and Eu3+ -L coordination bonding enable Eu3+ and L to self-assemble into shape-persistent 3D coordination metallogels in MeOH solution. The key to success is the utilization of crown ethers, playing dual roles of acting both as building blocks to build L with C2 -symmetrical structure, and as the ideal monomer for increasing the energy transfer from L to Eu3+ 's excited state, thus maintaining the excellent luminescence of metallogels. Interestingly, such assemblies show K+ , pH, F- , and mechano-induced reversible gel-sol transitions and tunable luminescence properties. Above findings are useful in the studies of molecular switches, dynamic assemblies, and smart luminescent materials.

Polysulfide Anions [Sx ]2- (x = 2, 3, 4, 5): Promising Functional Building Units for Infrared Nonlinear Optical Materials.

Infrared nonlinear optical (IR NLO) materials play significant roles in laser technology. The novel functional building units (FBUs) are of great importance in constructing NLO materials with strong second harmonic generation (SHG). Herein, polysulfide anion [Sx ]2- (x = 2, 3, 4, 5) units are investigated on NLO-related properties and structure-performance relationships. Theoretical calculations uncover that the [Sx ]2- (x = 2, 3, 4, 5) units are potential IR NLO FBUs with large polarizability anisotropy (δ), hyperpolarizability (ß) and wide HOMO-LUMO gap. Fourteen crystals including [Sx ]2- (x = 2, 3, 4, 5) units are calculated and analyzed. The results show that these units can result in a wide IR transmittance range, significant SHG effects, wide band gap Eg (Na2 S4 : Eg  = 3.09 eV), and large birefringence Δn [BaS3 (P21 21 2): Δn = 0.70]. More importantly, it is highlighted that the crystal materials including with [Sx ]2- (x = 2, 3, 4, 5) groups are good candidates for the exploration of the outstanding IR NLO materials.

Identifying novel disease categories through divergence optimization: An approach to prevent misdiagnosis in medical imaging.

Given the significant changes in human lifestyle, the incidence of colon cancer has rapidly increased. The diagnostic process can often be complicated due to symptom similarities between colon cancer and other colon-related diseases. In an effort to minimize misdiagnosis, deep learning-based approaches for colon cancer diagnosis have notably progressed within the field of clinical medicine, offering more precise detection and improved patient outcomes. Despite these advancements, practical application of these techniques continues to encounter two major challenges: 1) due to the need for expert annotation, only a limited number of labels are utilized for diagnosis; and 2) the existence of diverse disease types can lead to misdiagnosis when the model encounters unfamiliar disease categories. To overcome these hurdles, we present a method incorporating Universal Domain Adaptation (UniDA). By optimizing the divergence of samples in the source domain, our method detects noise. Furthermore, to identify categories that are not present in the source domain, we optimize the divergence of unlabeled samples in the target domain. Experimental validation on two gastrointestinal datasets demonstrates that our method surpasses current state-of-the-art domain adaptation techniques in identifying unknown disease classes. It is worth noting that our proposed method is the first work of medical image diagnosis aimed at the identification of unknown categories of diseases.

NaCl·CH4N2O·H2O: An Organic-Inorganic Hybrid Ultraviolet Nonlinear Optical Crystal with Optimized Comprehensive Properties.

Ultraviolet (UV) nonlinear optical (NLO) crystals are a vital component in laser systems to modulate frequency. Organic groups have the advantages of easy synthesis, structural diversity, and large hyperpolarizations (ß), which can be combined with inorganic groups to form unique organic-inorganic hybrid NLO crystal materials. Herein, a urea-containing crystal NaCl·CH4N2O·H2O is screened out and large-size crystals have been grown by a simple aqueous solution method. Compared with most reported organic-inorganic hybrid NLO materials, it has optimized comprehensive properties including a large SHG effect of 1.53 × KDP, a moderate birefringence (0.084@1064 nm), and a short UV cutoff edge of 209 nm. First-principles studies reveal that the dominant contributor to the linear and nonlinear optical properties is the urea molecule.

Mechanistic insights into the allosteric inactivation mechanism of ZAP-70 induced by the hot spot W165C mutation.

Zeta chain-associated protein kinase 70 (ZAP-70) is a non-receptor tyrosine kinase that interacts with the activated T-cell receptor to transduce downstream signals, and thus plays an important role in the adaptive immune system. The biphosphorylated immunotyrosine-based activation motifs (ITAM-Y2P) binds to the N-SH2 and C-SH2 domains of ZAP-70 to promote the activation of ZAP-70. The present study explores molecular mechanisms of allosteric inactivation of ZAP-70 induced by the hot spot W165C mutation through atomically detailed molecular dynamics simulation approaches. We report microsecond-length simulations of two states of the tandem SH2 domains of ZAP-70 in complex with the ITAM-Y2P motif, including the wild-type and W165C mutant. Extensive analysis of local flexibility and dynamical correlated motions show that W165C mutation changes coupled motions of protein domains and community networks. The binding affinities of the ITAM-Y2P motif to the wild-type and W165C mutant of ZAP-70 are predicted using binding free energy calculations. The results suggest that the driving force to decrease the binding affinity in the W165C mutant derives from the difference in the protein-protein electrostatic interactions. Moreover, the per-residue free energy decomposition unravels that the contributions from residues in the phosphorylated Tyr315 (pY315) binding site, in particular pY315 of ITAM-Y2P, and Arg43, Tyr240 of ZAP-70, are the key determinants for the loss of binding affinity. This study may insights into our understanding of the pathological mechanism of ZAP-70.Communicated by Ramaswamy H. Sarma.

Characterization of Lipid Alterations by Oncogenic PIK3CA Mutations Using Untargeted Lipidomics in Breast Cancer.

Lipids play crucial biological roles in health and disease, including in cancers. The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a pivotal promoter of cell growth and proliferation in various types of cancer. The somatic mutations in PIK3CA, the gene coding for the catalytic subunit p110α of PI3K, are frequently present in cancer cells, including breast cancer. Although the most prominent mutants, represented by single amino acid substitutions in the helical domain in exon 9 (E545K) and the kinase domain in exon 20 (H1047R) are known to cause a gain of PI3K function, activate AKT signaling and induce oncogenic transformation, the effect of these mutations on cellular lipid profiles has not been studied. We carried out untargeted lipidomics using liquid chromatography-tandem mass spectrometry to detect the lipid alterations in mammary gland epithelial MCF10A cells with isogenic knockin of these mutations. A total of 536 species of lipids were analyzed. We found that the levels of monosialogangliosides, signaling molecules known to enhance cell motility through PI3K/AKT pathway, were significantly higher in both mutants. In addition, triglycerides and ceramides, lipid molecules known to be involved in promoting lipid droplet production, cancer cell migration and invasion, were increased, whereas lysophosphatidylcholines and phosphatidylcholines that are known to inhibit cancer cell motility were decreased in both mutants. Our results provide novel insights into a potential link between altered lipid profile and carcinogenesis caused by the PIK3CA hotspot mutations. In addition, we suggest untargeted lipidomics offers prospects for precision/personalized medicine by unpacking new molecular substrates of cancer biology.

Self-strengthen luminescent hydrogel.

For typical synthetic materials, continue mechanical loading usually cause damage and even failure, because they are closed systems, without substance exchange with surroundings and structural reconstruction after damage. Double-network (DN) hydrogels have recently been demonstrated to generate radicals under mechanical loading. In this work, DN hydrogel provided with sustained monomer and lanthanide complex supply undergo self-growth, and thus simultaneous self-strengthen in both mechanical performance and luminescence intensity are realized through bond rupture-initiated mechanoradical polymerization. This strategy proves the feasibility of imparting desired functions to the DN hydrogel by mechanical stamping, and provides a new strategy for the design of luminescent soft materials with high fatigue resistance.

CsB3O4(OH)2: a new deep-ultraviolet birefringent crystal with [B3O4(OH)2] anionic group.

A new cesium hydroxyborate CsB3O4(OH)2, was designed and synthesized by a hydrothermal method. Remarkably, CsB3O4(OH)2 presents novel [B3O4(OH)2]∞ chains formed by [B3O4(OH)2] fundamental building blocks (FBBs). The report of less common [B3O4(OH)2] FBBs and [B3O4(OH)2]∞ chains in CsB3O4(OH)2 enriches the structural diversity of hydroxyborates. In addition, CsB3O4(OH)2 has a wide transparent window in the DUV spectral range and a large birefringence.

Double-Network Luminescent Films Constructed Using Sulfur Quantum Dots and Lanthanide Complexes.

Although UV light-switchable luminescent films are of importance for application in soft optical devices and anticounterfeiting labels, there are still challenges in developing such films integrated with outstanding luminescent property, high self-healing efficiency, and simultaneously excellent mechanical strength. Herein, double-network (DN) luminescent films are designed and constructed via an intermolecular hydrogen bond crosslinking strategy of poly(ethylene glycol) (PEG) in sulfur quantum dots (S-QDs) and polyurethane (PU), where S-QDs ("stone" one) play dual roles of acting both as a soft segment to crosslink another segment PU ("bird" one) and also as the origin of a luminescence center ("bird" two) in films. In addition, lanthanide(III) complexes (LnCs, Ln═Eu3+, Tb3+) are employed as another emission source to embed in the films and switch the emission colors of DN films from the multicolor (red-yellow-green) of LnCs to the blue color of S-QDs by changing the ultraviolet excitation wavelength from 254 to 365 nm. It is worth noting that the crosslinking network strategy can effectively prevent S-QDs and LnCs from aggregating or leaking and enable both luminescence centers to homogeneously distribute, resulting in luminescent DN films possessing extraordinary UV light-switchable luminescence, improved mechanical property, and excellent self-healing ability. This work presents a viable method for the design and fabrication of luminescent films with multifunctional applications in flexible robotics, wearable devices, and dual-luminescent anticounterfeiting materials.

From oxides to oxysulfides: the mixed-anion GeS3O unit induces huge improvement in the nonlinear optical effect and optical anisotropy for potential nonlinear optical materials.

Oxysulfides combining intrinsic performance advantages between sulfides (strong NLO response) and oxides (wide optical bandgap) are proposed as potential infrared (IR) NLO materials. Theoretical calculation shows that the mixed-anion GeS3O tetrahedron has a stronger polarizability anisotropy and hyperpolarizability than that of the typical GeO4 unit. Based on this, two Sr2MGe2S6O (M = Zn, Cd) oxysulfides with the GeS3O unit show dozens of times improvement in critical birefringence and the NLO effect compared with those of isostructural Sr2ZnGe2O7. Moreover, structure-property study further verifies that the mixed-anion GeS3O ligand is a useful NLO-active unit and can offer great influence over the NLO origin. This research result also gives us a feasible design strategy and research system to explore new IR NLO candidates.

Band gap modulation and nonlinear optical properties of quaternary tellurates Li2GeTeO6.

Tellurate crystals are attractive for developing new nonlinear optical (NLO) materials in the mid-infrared region due to their wide transmission window. In this work, we report a quaternary tellurate oxide crystal, Li2GeTeO6, which exhibits a short cutoff edge (240 nm) with a powder second harmonic generation (SHG) response of 1.3 × KH2PO4 (KDP). The reported material reveals the largest band gap in the Li2MTeO6 (M = tetravalent cation) family. The first-principles calculations were used to illustrate the origin of the NLO effect. These results highlight the band gap engineering based on the cation substitution strategy for designing new NLO materials with balanced optical properties.

Significant CO2 sink over the Tibet's largest lake: Implication for carbon neutrality across the Tibetan Plateau.

In this study, the CO2 flux over Siling Co Lake, the largest lake in Tibet, was analyzed employing the eddy covariance observation from 26 April 2014 to 22 March 2015. The results showed that Siling Co Lake acts as a net sink of CO2 with annual absorption of 315.5 g C m-2 a-1. The inorganic processes might be the main reason of CO2 absorption in Siling Co Lake owing to its high pH as an endorheic lake. Therefore, it is essential to consider the carbon absorption of lakes when assessing the carbon sink function of the Tibetan Plateau (TP). There would be more carbon surplus on the TP when the carbon absorption by lakes is considered, which will greatly contribute to the realization of carbon neutralization across TP. This study highlights the need to strengthen the systematic observation of long-term series of CO2 flux in lakes on the TP, and further analyse the mechanism of CO2 exchange between lakes and the atmosphere.

Performance optimization of support vector machine with oppositional grasshopper optimization for acute appendicitis diagnosis.

Preoperative differentiation of complicated and uncomplicated appendicitis is challenging. The research goal was to construct a new intelligent diagnostic rule that is accurate, fast, noninvasive, and cost-effective, distinguishing between complicated and uncomplicated appendicitis. Overall, 298 patients with acute appendicitis from the Wenzhou Central Hospital were recruited, and information on their demographic characteristics, clinical findings, and laboratory data was retrospectively reviewed and applied in this study. First, the most significant variables, including C-reactive protein (CRP), heart rate, body temperature, and neutrophils discriminating complicated from uncomplicated appendicitis, were identified using random forest analysis. Second, an improved grasshopper optimization algorithm-based support vector machine was used to construct the diagnostic model to discriminate complicated appendicitis (CAP) from uncomplicated appendicitis (UAP). The resultant optimal model can produce an average of 83.56% accuracy, 81.71% sensitivity, 85.33% specificity, and 0.6732 Matthews correlation coefficients. Based on existing routinely available markers, the proposed intelligent diagnosis model is highly reliable. Thus, the model can potentially be used to assist doctors in making correct clinical decisions.

Two lead borate-nitrates with anion-centered [OPb4] tetrahedra and two types of π-conjugated planar units showing large birefringence.

Two lead borate-nitrates Pb6O4(BO3)(NO3) and Pb6O2(BO3)2(NO3)F were obtained by the high-temperature flux method. Interestingly, their crystal structure consists of anion-centered [OPb4] tetrahedra and π-conjugated BO3 and NO3 units. The first principles calculations indicate that both compounds show large birefringence.

Inhibition of triple­negative breast cancer proliferation and motility by reactivating p53 and inhibiting overactivated Akt.

Mutations of p53 tumor suppressors occur more frequently in cancers at advanced stages or in more malignant cancer subtypes such as triple­negative breast cancer. Thus, restoration of p53 tumor suppressor function constitutes a valuable cancer therapeutic strategy. In the present study, it was revealed that a specific inhibitor of histone deacetylase 6, ACY­1215, caused increased acetylation of p53 in breast cancer cells with mutated p53, which was accompanied by increased expression of p21. These results suggested that ACY­1215 may lead to enhanced transcriptional activity of p53. It was also determined that ACY­1215 treatment resulted in G1 cell cycle arrest and apoptosis in these cancer cells. Furthermore, ACY­1215 displayed a synergistic effect with specific inhibitors of ATM, an activator of Akt, in inducing cancer cell apoptosis and inhibiting their motility. More importantly, it was observed that combination of ACY­1215 and ATM inhibitors exhibited markedly more potent antitumor activity than the individual compound in xenograft mouse models of breast cancer with mutant p53. Collectively, our results demonstrated that ACY­1215 is a novel chemotherapeutic agent that could restore mutant p53 function in cancer cells with strong antitumor activity, either alone or in combination with inhibitors of the ATM protein kinase.

Evolving kernel extreme learning machine for medical diagnosis via a disperse foraging sine cosine algorithm.

Kernel extreme learning machine (KELM) has been widely used in the fields of classification and identification since it was proposed. As the parameters in the KELM model have a crucial impact on performance, they must be optimized before the model can be applied in practical areas. In this study, to improve optimization performance, a new parameter optimization strategy is proposed, based on a disperse foraging sine cosine algorithm (DFSCA), which is utilized to force some portions of search agents to explore other potential regions. Meanwhile, DFSCA is integrated into KELM to establish a new machine learning model named DFSCA-KELM. Firstly, using the CEC2017 benchmark suite, the exploration and exploitation capabilities of DFSCA were demonstrated. Secondly, evaluation of the model DFSCA-KELM on six medical datasets extracted from the UCI machine learning repository for medical diagnosis proved the effectiveness of the proposed model. At last, the model DFSCA-KELM was applied to solve two real medical cases, and the results indicate that DFSCA-KELM can also deal with practical medical problems effectively. Taken together, these results show that the proposed technique can be regarded as a promising tool for medical diagnosis.