Recent Advances on the Functionalities of Polyoxometalate-Based Ionic Liquids.

Polyoxometalate (POM)-based ionic liquids (POM-ILs) are gaining increasing attention due to their diverse structures and functionalities. POMs in POM-ILs not only act as essential structural building blocks but also play a crucial role in their functional performance. With the incorporation of POMs, POM-ILs find applications in various fields such as chemical catalysis, energy science, materials science, sensors, and more. The abundant availability of POMs and other building blocks in POM-ILs, along with their versatile combination possibilities, present promising opportunities for the future. Rather than focusing solely on discovering new structures of POM-ILs, current developments in this field emphasize exploring their functions, leading to the emergence of numerous new applications. Summarizing these advancements aids in understanding the latest trends and facilitates rapid evolution. This review examines the recent five years' worth of results to analyze the new functions of POM-ILs, categorizing them based on their unique characteristics.

Fully Printed Multilayer Ceramic Capacitors Based on High-k Perovskite Nanosheets.

Printing technology enables the integration of chemically exfoliated perovskite nanosheets into high-performance microcapacitors. Theoretically, the capacitance value can be further enhanced by designing and constructing multilayer structures without increasing the device size. Yet, issues such as interlayer penetration in multilayer heterojunctions constructed using inkjet printing technology further limit the realization of this potential. Herein, a series of multilayer configurations, including Ag/(Ca2NaNb4O13/Ag)n and graphene/(Ca2NaNb4O13/graphene)n (n = 1-3), are successfully inkjet-printed onto diverse rigid and flexible substrates through optimized ink formulations, inkjet printing parameters, thermal treatment conditions, and rational multilayer structural design using high-k perovskite nanosheets, graphene nanosheets and silver. The dielectric performance is optimized by fine-tuning the number of dielectric layers and modifying the electrode/dielectric interface. As a result, the graphene/(Ca2NaNb4O13/graphene)3 multilayer ceramic capacitors exhibit a remarkable capacitance density of 346 ± 12 nF cm-2 and a high dielectric constant of 193 ± 18. Additionally, these devices demonstrate moderate insulation properties, flexibility, thermal stability, and chemical sensitivity. This work shed light on the potential of multilayer structural design in additive manufacturing of high-performance 2D material-based ceramic capacitors.

Rational Construction of a 3D Self-Supported Electrode Based on ZIF-67 and Amorphous NiCoP for an Enhanced Oxygen Evolution Reaction.

The development of efficient and Earth-abundant electrocatalysts for the oxygen evolution reaction (OER) is an urgent requirement in the field of electrochemical water splitting. The electrocatalytic performance of the OER can be greatly enhanced by the synergistic combination of zeolite imidazolate frameworks (ZIFs) and transition-metal phosphides, both of which individually exhibit promising capabilities in this regard. In this study, a novel amorphous NiCoP deposited on ZIF-67 sheets supported on Ni foam (labeled as NiCoP/ZIF-67/NF) as an OER electrocatalytic material was successfully synthesized using a simple, secure, and time-efficient two-step strategy. The experimental results demonstrate that NiCoP/ZIF-67/NF possesses a large active surface area with abundant active sites. Also, the synergistic effect and interaction between NiCoP and ZIF-67, as well as between Ni and Co within NiCoP, effectively enhance its electrochemical performance under alkaline conditions. Consequently, NiCoP/ZIF-67/NF exhibits outstanding catalytic activity for OER with an overpotential (η) of 175 mV at a current density of 10 mA cm-2 and a long-term stability over 40 h at 20 mA cm-2 in a 1.0 M KOH electrolyte. The corresponding analyses suggest that the real active sites responsible for the OER are identified as NiOOH and CoOOH species within the structure of NiCoP/ZIF-67/NF. Additionally, the catalytic function and stability of ZIF-67 toward the OER under alkaline conditions were also briefly discussed. This work provides a novel catalytic material for the OER along with a facile strategy to fabricate superior, efficient, and noble metal-free catalysts suitable for energy-related applications.

[Effectiveness analysis of double EndoButton suture fixation Latarjet procedure for treatment of anterior shoulder dislocation with glenoid bone defect caused by military training injuries].

Objective: To investigate the effectiveness of double EndoButton suture fixation Latarjet procedure in the treatment of shoulder anterior dislocation with glenoid bone defect caused by military training injuries. Methods: The clinical data of 14 patients with anterior shoulder dislocation with glenoid bone defect due to military training injuries who met the selection criteria and admitted between August 2021 and December 2022 were retrospectively analyzed. All patients were male, the age ranged from 21 to 38 years, with an average of 26.8 years. The time from initial dislocation to operation was 6-15 months, with an average of 10.2 months. Anterior shoulder dislocation occurred 5-12 times, with an average of 8.2 times. All glenoid bone defects were more than 10%, including 5 cases of 10%-15%, 8 cases of 15%-20%, and 1 case of 24%. All patients were treated by double EndoButton suture fixation Latarjet procedure. The operation time and complications were recorded. The shoulder function and pain were evaluated by the American Association for Shoulder and Elbow Surgery (ASES) score, Rowe score, Instability Severity Index Score (ISIS), and visual analogue scale (VAS) score before and after operation. The range of motion of the shoulder was recorded, including forward flexion, 0° external rotation, and abduction 90° external rotation. The position, healing, and resorption of the bone mass were evaluated by three-dimensional CT of shoulder joint after operation. Results: All patients successfully completed the operation, and the operation time was 100-150 minutes, with an average of 119.7 minutes. There was no complications such as infection, vascular and nerve injury. All patients were followed up 12-20 months, with an average of 15.6 months. During the follow-up, 4 patients had bone mass separation, absorption, and recurrent anterior dislocation, and the shoulder joint fear test was positive. Imaging of the remaining patients showed that the bone mass healed well, no anterior dislocation recurrence occurred, and the healing time was 3-7 months (mean, 4.7 months). At last follow-up, the range of motion, ASES score, Rowe score, ISIS score, and VAS score of the patients significantly improved when compared with those before operation ( P<0.05). Conclusion: The effectiveness of double EndoButton suture fixation Latarjet procedure for the treatment of anterior shoulder dislocation with glenoid bone defect caused by military training injury is satisfactory.

Molecular Insight into the Processes and Mechanisms of N2 Adsorption and Accumulation at the Hydrophobic Solid/Liquid Interface.

In this study, molecular dynamics (MD) simulations were employed to elucidate the processes and underlying mechanisms that govern the adsorption and accumulation of gas (represented by N2) at the hydrophobic solid-liquid interface, using the GROMACS program with an AMBER force field. Our findings indicate that, regardless of surface roughness, the presence of water molecules is a prerequisite for the adsorption and aggregation of N2 molecules on solid surfaces. N2 molecules dissolved in water can cluster even without a solid substrate. In the gas-solid-liquid system, the exclusion of water molecules at the hydrophobic solid-liquid interface and the adsorption of N2 molecules do not occur simultaneously. A loosely arranged layer of water molecules is initially formed on the hydrophobic solid surface. The two-stage process of N2 molecule adsorption and accumulation at the hydrophobic solid/liquid interface involves initial adsorption to the solid surface, displacing water molecules, followed by N2 accumulation via self-interaction after saturating the substrate's surface. The process and underlying mechanisms of gas adsorption and accumulation at hydrophobic solid/liquid interfaces elucidated in this study offer a molecular-level understanding of nano-gas layer formation.

WITHDRAWN: Coronary artery segmentation based on ACMA-Net and unscented Kalman filter algorithm.

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LncRNA AFAP1-AS1 Promotes Oral Squamous Cell Carcinoma Development by Ubiquitin-Mediated Proteolysis.

BACKGROUND AND PURPOSE: Long noncoding RNA (lncRNA) dysregulation has been reported to play a pivotal role in the development of cancers. In this study, we aimed to screen the key lncRNA in oral squamous cell carcinoma (OSCC) via bioinformatics analysis and further validate the function of lncRNA in vitro and in vivo. METHODS: Bioinformatics analysis was conducted to identify differentially expressed lncRNAs between control and OSCC samples. Quantitative real-time-polymerase chain reaction was employed to detect the expression of differentially expressed lncRNAs in human tongue squamous cell carcinoma and human oral keratinocytes cell lines. The biological function of lncRNA and its mechanism were examined via the experimental assessment of the cell lines with the lncRNA overexpressed and silenced. Additionally, to further explore the function of lncRNA in the progression of OSCC, xenograft tumour mouse models were established using 25 mice (5 groups, each with 5 mice). Tumour formation was observed at 2 weeks after the cell injection, and the tumours were resected at 5 weeks post-implantation. RESULTS: Two lncRNAs, LINC00958 and AFAP1-AS1, were found to be correlated with the prognosis of OSCC. The results of the quantitative real-time-polymerase chain reaction indicated that the 2 lncRNAs were highly expressed in OSCC. In combination with the previous literature, we found AFAP1-AS1 to be a potentially important biomarker for OSCC. Thus, we further investigated its biological function and found that AFAP1-AS1 silencing inhibited cell proliferation, migration, and invasion whereas AFAP1-AS1 overexpression reversed the effect of AFAP1-AS1 silencing (P < .05). Mechanism analysis revealed that AFAP1-AS1 regulated the development of OSCC through the ubiquitin-mediated proteolysis pathway. CONCLUSIONS: AFAP1-AS1 is an oncogene that aggravates the development of OSCC via the ubiquitin-mediated proteolysis pathway. It also provides a novel potential therapy for OSCC.

[Ecological characteristics and seasonal changes of macrozoobenthos in the waters of Miaodao Archipelago, China]. / åº™å²›ç¾¤å²›æµ·åŸŸå¤§åž‹åº•æ –åŠ¨ç‰©ç”Ÿæ€ç‰¹å¾åŠå­£èŠ‚å˜åŒ–.

To understand the macrozoobenthic community composition and spatial-temporal distribution characteristics of macrobenthos in the waters of Miaodao Archipelago, Yantai, Shandong and its response to habitat changes, we conducted surveys of macrobenthos and environmental elements in the waters of Miaodao Islands in May (spring), August (summer), and October (autumn) in 2022. Results showed that a total of 127 macrozoobenthic species were recorded, with Mollusca and Annelida (Polychaeta) as the dominant taxa, consisting of 47 and 45 species, respectively. The key dominant species included Sternaspis chinensis, Glycinde bonhourei, Moerella hilaris, and Amphioplus (Lymanella) japonicus. The average annual density and biomass of macrozoobenthos were 190 ind·m-2 and 28.69 g·m-2, respectively. There was no significant seasonal differences in density and biomass. The Shannon diversity index (H), evenness index (J), and richness index (D) averaged 3.10, 0.90, and 2.40, respectively. Cluster analysis results showed low similarity coefficients of community among the three seasons, suggesting a distinct distribution pattern. Factors such as bottom seawater temperature, chlorophyll a, nutrient, sediment grain size, and organic matter content could significantly influence the structure and diversity of macrozoobenthic community. Compared with historical research data, the Changdao National Wetland Nature Reserve and the implementation of enclosure aquaculture have led to notable changes in the dominant species of macrobenthos. Specifically, there was a noticeable decline in both density and H, and an increase in biomass and J. Additionally, body size of benthic fauna was transitioning from small to big.

2D Exfoliation Chemistry Towards Covalent Pseudo-Layered Phosphate Framework Derived by Radical/Strain-Synergistical Process.

2D compounds exfoliated from weakly bonded bulk materials with van der Waals (vdW) interaction are easily accessible. However, the strong internal ionic/covalent bonding of most inorganic crystal frameworks greatly hinders 2D material exfoliation. Herein, we first proposed a radical/strain-synergistic strategy to exfoliate non-vdW interacting pseudo-layered phosphate framework. Specifically, hydroxyl radicals (⋅OH) distort the covalent bond irreversibly, meanwhile, H2O molecules as solvents, further accelerating interlayered ionic bond breakage but mechanical expansion. The innovative 2D laminar NASICON-type Na3V2(PO4)2O2F crystal, exfoliated by ⋅OH/H2O synergistic strategy, exhibits enhanced sodium-ion storage capacity, high-rate performance (85.7 mAh g-1 at 20 C), cyclic life (2300 cycles), and ion migration rates, compared with the bulk framework. Importantly, this chemical/physical dual driving technique realized the effective exfoliation for strongly coupled pseudo-layered frameworks, which accelerates 2D functional material development.

SlPP2C2 interacts with FZY/SAUR and regulates tomato development via signaling crosstalk of ABA and auxin.

Abscisic acid (ABA) signaling interacts frequently with auxin signaling when it regulates plant development, affecting multiple physiological processes; however, to the best of our knowledge, their interaction during tomato development has not yet been reported. Here, we found that type 2C protein phosphatase (SlPP2C2) interacts with both flavin monooxygenase FZY, an indole-3-acetic acid (IAA) biosynthetic enzyme, and small auxin upregulated RNA (SAUR) of an IAA signaling protein and regulates their activity, thereby affecting the expression of IAA-responsive genes. The expression level of SlPP2C2 was increased by exogenous ABA, IAA, NaCl, or dehydration treatment of fruits, leaves, and seeds, and it decreased in imbibed seeds. Manipulating SlPP2C2 with overexpression, RNA interference, and CRISPR/Cas9-mediated genome editing resulted in pleiotropic changes, such as morphological changes in leaves, stem trichomes, floral organs and fruits, accompanied by alterations in IAA and ABA levels. Furthermore, the RNA-seq analysis indicated that SlPP2C2 regulates the expression of auxin-/IAA-responsive genes in different tissues of tomato. The results demonstrate that SlPP2C2-mediated ABA signaling regulates the development of both vegetative and reproductive organs via interaction with FZY/SAUR, which integrates the cross-talk of ABA and auxin signals during development and affects the expressions of development-related genes in tomato.

Serum cytokines and creatinine/cystatin C ratio as prognostic biomarkers in advanced cancer patients treated with anti-PD-1/PD-L1 therapy.

OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.

Direct Ink Writing of Low-Concentration MXene/Aramid Nanofiber Inks for Tunable Electromagnetic Shielding and Infrared Anticounterfeiting Applications.

MXene inks offer a promising avenue for the scalable production and customization of printing electronics. However, simultaneously achieving a low solid content and printability of MXene inks, as well as mechanical flexibility and environmental stability of printed objects, remains a challenge. In this study, we overcame these challenges by employing high-viscosity aramid nanofibers (ANFs) to optimize the rheology of low-concentration MXene inks. The abundant entangled networks and hydrogen bonds formed between MXene and ANF significantly increase the viscosity and yield stress up to 103 Pa·s and 200 Pa, respectively. This optimization allows the use of MXene/ANF (MA) inks at low concentrations in direct ink writing and other high-viscosity processing techniques. The printable MXene/ANF inks with a high conductivity of 883.5 S/cm were used to print shields with customized structures, achieving a tunable electromagnetic interference shielding effectiveness (EMI SE) in the 0.2-48.2 dB range. Furthermore, the MA inks exhibited adjustable infrared (IR) emissivity by changing the ANF ratio combined with printing design, demonstrating the application for infrared anticounterfeiting. Notably, the printed MXene/ANF objects possess outstanding mechanical flexibility and environmental stability, which are attributed to the reinforcement and protection of ANF. Therefore, these findings have significant practical implications as versatile MXene/ANF inks can be used for customizable, scalable, and cost-effective production of flexible printed electronics.

The usage and costs of national drug price-negotiated anticancer medicines in a first-tier city in Northeast China: a study based on health insurance data.

BACKGROUND: The National Drug Price Negotiation (NDPN) policy has entered a normalisation stage, aiming to alleviate, to some extent, the disease-related and economic burdens experienced by cancer patients. This study analysed the use and subsequent burden of anticancer medicines among cancer patients in a first-tier city in northeast China. METHODS: We assessed the usage of 64 negotiated anticancer medicines using the data on the actual drug deployment situation, the frequency of medical insurance claims and actual medication costs. The affordability of these medicines was measured using the catastrophic health expenditure (CHE) incidence and intensity of occurrence. Finally, we used the defined daily doses (DDDs) and defined daily doses cost (DDDc) as indicators to evaluate the actual use of these medicines in the region. RESULTS: During the study period, 63 of the 64 medicines were readily available. From the perspective of drug usage, the frequency of medical insurance claims for negotiated anticancer medicines and medication costs showed an increasing trend from 2018 to 2021. Cancer patients typically sought medical treatment at tertiary hospitals and purchased medicines at community pharmacies. The overall quantity and cost of medications for patients covered by the Urban Employee Basic Medical Insurance (UEBMI) were five times higher than those covered by the Urban and Rural Resident Medical Insurance (URRMI). The frequency of medical insurance claims and medication costs were highest for lung and breast cancer patients. Furthermore, from 2018 to 2021, CHE incidence showed a decreasing trend (2.85-1.60%) under urban patients' payment capability level, but an increasing trend (11.94%-18.42) under rural patients' payment capability level. The average occurrence intensities for urban (0.55-1.26 times) and rural (1.27-1.74 times) patients showed an increasing trend. From the perspective of drug utilisation, the overall DDD of negotiated anticancer medicines showed an increasing trend, while the DDDc exhibited a decreasing trend. CONCLUSION: This study demonstrates that access to drugs for urban cancer patients has improved. However, patients' medical behaviours are affected by some factors such as hospital level and type of medical insurance. In the future, the Chinese Department of Health Insurance Management should further improve its work in promoting the fairness of medical resource distribution and strengthen its supervision of the nation's health insurance funds.

Regulation of Myc transcription by an enhancer cluster dedicated to pluripotency and early embryonic expression.

MYC plays various roles in pluripotent stem cells, including the promotion of somatic cell reprogramming to pluripotency, the regulation of cell competition and the control of embryonic diapause. However, how Myc expression is regulated in this context remains unknown. The Myc gene lies within a ~ 3-megabase gene desert with multiple cis-regulatory elements. Here we use genomic rearrangements, transgenesis and targeted mutation to analyse Myc regulation in early mouse embryos and pluripotent stem cells. We identify a topologically-associated region that homes enhancers dedicated to Myc transcriptional regulation in stem cells of the pre-implantation and early post-implantation embryo. Within this region, we identify elements exclusively dedicated to Myc regulation in pluripotent cells, with distinct enhancers that sequentially activate during naive and formative pluripotency. Deletion of pluripotency-specific enhancers dampens embryonic stem cell competitive ability. These results identify a topologically defined enhancer cluster dedicated to early embryonic expression and uncover a modular mechanism for the regulation of Myc expression in different states of pluripotency.

Design of a polarization-multiplexed, high-resolution, near-field focusing metasurface lens.

To meet the requirements of integrated and high-resolution focusing devices for passive millimeter-wave (PMMW) imaging systems, a polarization-multiplexed high-resolution near-field focusing metasurface lens is proposed. Metasurface units consist of two dielectric layers and three metal layers and are designed with a multiarm windmill structure. This design allows the units to independently control the electromagnetic response of incident x-polarized and y-polarized waves while maintaining a thickness of only 0.16λ (2 mm). The metasurface lens that can achieve dual-channel near-field focusing was designed by combining the focusing principle of the metasurface lens and phase superposition principle based on the above design. The lens consists of 30×30 units and has a size of 120×120m m 2. According to the simulation results, the lens is able to focus the y-polarized waves of 24 GHz at z=50m m plane with a focal spot size of 0.68λ (8.5 mm), and the focusing beam efficiency is 35.2%. Similarly, the x-polarized waves of 24 GHz are focused at z=70m m plane with a focal spot size of 0.72λ (9 mm), and the focusing beam efficiency is 40.7%. The proposed metasurface lens is promising for applications in PMMW imaging systems, medical sensors, automotive millimeter-wave radar, and other related fields, owing to the characteristics of high resolution, compact size, and multifunctionality.

Dynamical modulation of hypersynchronous seizure onset with transcranial magneto-acoustic stimulation in a hippocampal computational model.

Hypersynchronous (HYP) seizure onset is one of the frequently observed seizure-onset patterns in temporal lobe epileptic animals and patients, often accompanied by hippocampal sclerosis. However, the exact mechanisms and ion dynamics of the transition to HYP seizures remain unclear. Transcranial magneto-acoustic stimulation (TMAS) has recently been proposed as a novel non-invasive brain therapy method to modulate neurological disorders. Therefore, we propose a biophysical computational hippocampal network model to explore the evolution of HYP seizure caused by changes in crucial physiological parameters and design an effective TMAS strategy to modulate HYP seizure onset. We find that the cooperative effects of abnormal glial uptake strength of potassium and excessive bath potassium concentration could produce multiple discharge patterns and result in transitions from the normal state to the HYP seizure state and ultimately to the depolarization block state. Moreover, we find that the pyramidal neuron and the PV+ interneuron in HYP seizure-onset state exhibit saddle-node-on-invariant-circle/saddle homoclinic (SH) and saddle-node/SH at onset/offset bifurcation pairs, respectively. Furthermore, the response of neuronal activities to TMAS of different ultrasonic waveforms revealed that lower sine wave stimulation can increase the latency of HYP seizures and even completely suppress seizures. More importantly, we propose an ultrasonic parameter area that not only effectively regulates epileptic rhythms but also is within the safety limits of ultrasound neuromodulation therapy. Our results may offer a more comprehensive understanding of the mechanisms of HYP seizure and provide a theoretical basis for the application of TMAS in treating specific types of seizures.

Fluorescence Switching and Photoisomerization of a Spiropyran Molecular Photoswitch through Confined Spaces Regulation in Crystals.

Spiropyran (SP) and its derivatives are highly attractive owing to their distinctive merits in high contrast and fast response read-out systems. However, the realization of photoswitching properties of SP is hindered in the aggregate state, particularly in crystals owing to the dense packing of molecules leading to insufficient study of the relationship between the molecular structure/stacking mode and photoswitching behavior. Herein, we report three SP derivatives: different flexible chains (carboxyl group for SP-0 and ester group for SP-1) are attached to the indoline moiety, while the ester group is attached to the chromene moiety for SP-2. SP-1 exhibits fluorescent photoswitching properties in crystals due to the weak intermolecular interactions resulting in enough free space for the photoisomerization. The presence of hydrogen bonds in SP-0 enhances the molecular interactions to restrict the photoisomerization, and the ester group of SP-2 impacts the thermodynamic properties, thereby limiting the realization of photoswitching of SP-2.

Deep-learning-based real-time individualization for reduce-order haemodynamic model.

The reduced-order lumped parameter model (LPM) has great computational efficiency in real-time numerical simulations of haemodynamics but is limited by the accuracy of patient-specific computation. This study proposed a method to achieve the individual LPM modeling with high accuracy to improve the practical clinical applicability of LPM. Clinical data was collected from two medical centres comprising haemodynamic indicators from 323 individuals, including brachial artery pressure waveforms, cardiac output data, and internal carotid artery flow waveforms. The data were expanded to 5000 synthesised cases that all fell within the physiological range of each indicator. LPM of the human blood circulation system was established. A double-path neural network (DPNN) was designed to input the waveforms of each haemodynamic indicator and their key features and then output the individual parameters of the LPM, which was labelled using a conventional optimization algorithm. Clinically collected data from the other 100 cases were used as the test set to verify the accuracy of the individual LPM parameters predicted by DPNN. The results show that DPNN provided good convergence in the training process. In the test set, compared with clinical measurements, the mean differences between each haemodynamic indicator and the estimate calculated by the individual LPM based on the DPNN were about 10 %. Furthermore, DPNN prediction only takes 4 s for 100 cases. The DPNN proposed in this study permits real-time and accurate individualization of LPM's. When facing medical issues involving haemodynamics, it lays the foundation for patient-specific numerical simulation, which may be beneficial for potential clinical application.

Effectiveness and tolerability of programmed cell death protein-1 inhibitor + chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers.

BACKGROUND: The combination of programmed cell death protein-1 (PD-1) inhibitor and chemotherapy is approved as a standard first- or second-line treatment in patients with advanced oesophageal or gastric cancer. However, it is unclear whether this combination is superior to chemotherapy alone. AIM: To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer, gastroesophageal junction (GEJ) cancer, or oesophageal carcinoma. METHODS: We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer. We employed either random or fixed models to analyze the outcomes of each clinical trial, encompassing data on overall survival (OS), progression-free survival (PFS), objective response rate, and adverse events (AEs). RESULTS: Nine phase 3 clinical trials (7016 advanced oesophageal and gastric cancer patients) met the inclusion criteria. Our meta-analysis demonstrated that the pooled PD-1 inhibitor + chemotherapy group had a significantly longer OS than the chemotherapy-alone group [hazard ratio (HR) = 0.76, 95% confidence interval (CI): 0.71-0.81]; the pooled PFS result was consistent with that of OS (HR = 0.67, 95%CI: 0.61-0.74). The count of patients achieving an objective response in the PD-1 inhibitor + chemotherapy group surpassed that of the chemotherapy-alone group [odds ratio (OR) = 1.86, 95%CI: 1.59-2.18]. AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group, regardless of whether ≥ grade 3 only (OR = 1.30, 95%CI: 1.07-1.57) or all AE grades (OR = 1.88, 95%CI: 1.39-2.54) were examined. We performed a subgroup analysis based on the programmed death-ligand 1 (PD-L1) combined positive score (CPS) and noted extended OS and PFS durations within the CPS ≥ 1, CPS ≥ 5, and CPS ≥ 10 subgroups of the PD-1 inhibitor + chemotherapy group. CONCLUSION: In contrast to chemotherapy alone, the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer, GEJ tumor, or oesophageal cancer. This holds true particularly for individuals with PD-L1 CPS scores of ≥ 5 and ≥ 10.

Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer and a significant cause of cancer-related mortality globally. Resistance to chemotherapy, especially during CRC treatment, leads to reduced effectiveness of drugs and poor patient outcomes. Long noncoding RNAs (lncRNAs) have been implicated in various pathophysiological processes of tumor cells, including chemotherapy resistance, yet the roles of many lncRNAs in CRC remain unclear. AIM: To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this resistance. METHODS: Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin resistance. Various bioinformatics tools were employed to elucidate molecular mechanisms. The expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain reaction. Functional assays, including MTT, wound healing, and Transwell, were conducted to investigate the functional implications of lncRNA alterations. Interactions between lncRNAs and transcription factors were examined using RIP and luciferase reporter assays, while Western blotting was used to confirm downstream pathways. Additionally, a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy resistance. RESULTS: LncRNA prion protein testis specific (PRNT) was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2 (HIPK2) expression. PRNT was demonstrated to sponge transcription factor zinc finger protein 184 (ZNF184), which in turn could regulate HIPK2 expression. Altered expression of PRNT influenced CRC cell sensitivity to oxaliplatin, with overexpression leading to decreased sensitivity and decreased expression reducing resistance. Both RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of PRNT. The PRNT/ZNF184/HIPK2 axis was implicated in promoting CRC progression and oxaliplatin resistance both in vitro and in vivo. CONCLUSION: The study concludes that PRNT is upregulated in oxaliplatin-resistant CRC cells and modulates the expression of HIPK2 by sponging ZNF184. This regulatory mechanism enhances CRC progression and resistance to oxaliplatin, positioning PRNT as a promising therapeutic target for CRC patients undergoing oxaliplatin-based chemotherapy.