Analysis of the effect of cations on protein conformational stability using solid-state nanopores.

The conformation of proteins is closely related to their biological functions, and it is affected by many factors, including the type of cations in solution. However, it is difficult to detect the conformational changes of a protein in situ. As a single-molecule sensing technology, nanopores can convert molecular structural information into analyzable current signals within a reasonable time range. Herein, we detect and analyze the effects of two different types of monovalent cations (Na+ and Li+) on a model protein bovine serum albumin (BSA) conformation using SiNx nanopores with different diameters. The quantitative analysis results show that the excluded volume of BSA in LiCl salt solutions is larger than the value in NaCl solution, indicating that Li+ is more prone to unfolding the proteins and making them unstable. This study demonstrated that nanopores enable the in situ detection of the structure of proteins at the single-molecule level and provide a new approach for the quantitative analysis of proteins.

Association of socioeconomic status and overactive bladder in US adults: a cross-sectional analysis of nationally representative data.

Background: Socioeconomic status inequality is an important variable in the emergence of urological diseases in humans. This study set out to investigate the association between the prevalence of overactive bladder (OAB) and the poverty income ratio (PIR) that served as a more influential indicator of socioeconomic status compared to education and occupation. Method: Data from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2020 were used in this cross-sectional study. The association between the PIR and OAB was examined using weighted multivariate logistic regression and weighted restricted cubic splines (RCS). Additionally, interaction analysis was used for investigation to the connections between PIR and OAB in various covariate groups in order to confirm the stability of the results. Results: We observed a noteworthy inverse association between PIR and OAB after adjusting for potential confounding variables (OR = 0.87, 95% CI, 0.84-0.90, p < 0.0001). PIR was transformed into categorical variables, and the association held steady after that (1.0 < PIR <4.0 vs. PIR ≤ 1.0, OR = 0.70, 95% CI =0.63-0.77, p < 0.0001; PIR ≥ 4.0 vs. PIR ≤ 1.0, OR = 0.56, 95% CI =0.48-0.65, p < 0.0001). Additionally, RCS analysis showed that PIR and OAB had a negative nonlinear response relationship. Subgroup analyses showed that the inverse association between PIR and prevalence of OAB was stronger in obese than in nonobese individuals (P for interaction < 0.05). Conclusion: In our study, we observed a significant negative association between the PIR and the prevalence of OAB. In the future, PIR could be used as a reference standard to develop strategies to prevent and treat OAB.

Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons.

G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are important drug targets. The discovery of drugs targeting these receptors and their G protein signaling properties are based on assays mainly performed with modified receptors expressed in heterologous cells. However, GPCR responses may differ in their native environment. Here, by using highly sensitive Gi/o sensors, we reveal specific properties of Gi/o protein-mediated responses triggered by GABAB, α2 adrenergic and cannabinoid CB1 receptors in primary neurons, different from those in heterologous cells. These include different profiles in the Gi/o protein subtypes-mediated responses, and differences in the potencies of some ligands even at similar receptor expression levels. Altogether, our results show the importance of using biosensors compatible with primary cells for evaluating the activities of endogenous GPCRs in their native environment.

An in vitro-transcribed circular RNA targets the mitochondrial inner membrane cardiolipin to ablate EIF4G2+/PTBP1+ pan-adenocarcinoma.

In vitro-transcribed (IVT) mRNA has arisen as a rapid method for the production of nucleic acid drugs. Here, we have constructed an oncolytic IVT mRNA that utilizes human rhinovirus type 2 (HRV2) internal ribosomal entry sites (IRESs) to selectively trigger translation in cancer cells with high expression of EIF4G2 and PTBP1. The oncolytic effect was provided by a long hGSDMDc .825 T>A/c.884 A>G-F1LCT mutant mRNA sequence with mitochondrial inner membrane cardiolipin targeting toxicity that triggers mitophagy. Utilizing the permuted intron-exon (PIE) splicing circularization strategy and lipid nanoparticle (LNP) encapsulation reduced immunogenicity of the mRNA and enabled delivery to eukaryotic cells in vivo. Engineered HRV2 IRESs-GSDMDp.D275E/E295G-F1LCT circRNA-LNPs (GSDMDENG circRNA) successfully inhibited EIF4G2+/PTBP1+ pan-adenocarcinoma xenografts growth. Importantly, in a spontaneous tumor model with abnormal EIF4G2 and PTBP1 caused by KRAS G12D mutation, GSDMDENG circRNA significantly prevented the occurrence of pancreatic, lung and colon adenocarcinoma, improved the survival rate and induced persistent KRAS G12D tumor antigen-specific cytotoxic T lymphocyte responses.

Optimizing the extraction of active components from Salvia miltiorrhiza by combination of machine learning models and intelligent optimization algorithms and its correlation analysis of antioxidant activity.

We extracted Sal B and TIIA from Salvia miltiorrhiza using enzymatic-assisted ethanol extraction. ACONN predicted optimal process conditions. Enzymolysis and alcohol extraction were used, optimizing conditions and evaluating antioxidant activity. ACONN analyzed data and ACO optimized conditions. Lab verification comprehensively evaluated the conditions. The correlation between Sal B, TIIA, and their antioxidant activities was examined. Weights of 0.5739 and 0.4260 evaluated Sal B and TIIA. ACONN had a 97.46% fitting degree. Optimized extraction conditions improved yield and quality, yielding a comprehensive evaluation value of 27.69 with 4.46% average errors. This approach enhances extraction and compound quality. Antioxidant activity strongly correlated with component yield, influenced by extraction conditions. ACONN-optimized extraction improved Sal B and TIIA yield and quality, with potential as natural antioxidants. Integrating machine learning and optimization algorithms in industrial extraction enhances efficiency and environmental preservation.

Endoplasmic reticulum stress-mediated autophagy alleviates lipopolysaccharide-induced nucleus pulposus cell pyroptosis by inhibiting CHOP signaling in vitro.

Pyroptosis, a newly discovered pro-inflammatory programmed necrosis of cells, serves as an initiating and promoting event that leads to intervertebral disc (IVD) degeneration (IDD). Endoplasmic reticulum stress (ERS) and autophagy are vital regulatory mechanisms of cellular homeostasis, which is also closely related to IDD. However, the role and relationship of ERS and autophagy in the pyroptosis of nucleus pulposus cell (NPC) are not well understood. In this research, we aimed to elucidate the role and mechanism of ERS-C/EBP homologous protein (CHOP) in lipopolysaccharide (LPS)-induced cell pyroptosis and determine its interaction with autophagy. ERS and autophagy inducers or inhibitors were used or not in the preconditioning of rat NPCs. Cell viability, pyroptosis-related protein expression, caspase-1 activity assay, and enzyme-linked immunosorbent assay were performed to observe rat NPC pyroptosis after the treatment of LPS. Activation of the ERS pathway and autophagy were assessed by quantitative real-time PCR, western blot analyses, and immunofluorescence staining assay to classify the molecular mechanisms. Our results showed that LPS stimulation induced NPC pyroptosis with concomitant activation of the ERS-CHOP pathway and initiated autophagy. Activation of the ERS-CHOP pathway exacerbated rat NPC pyroptosis, whereas autophagy inhibited cell pyroptosis. LPS-induced cell pyroptosis and CHOP upregulation were negatively regulated by autophagy. LPS-induced autophagy was depressed by the ERS inhibitor but aggravated by the ERS inducer. Taken together, our findings suggested that LPS induced NPC pyroptosis by activating ERS-CHOP signaling and ERS mediated LPS-induced autophagy, which in turn alleviated NPC pyroptosis by inhibiting CHOP signaling.

LACC1 regulates changes in the intestinal flora in a mouse model of inflammatory bowel disease.

BACKGROUND: The aim of this study was to explore the mechanism whereby LACC1 regulates the intestinal flora in a mouse model of inflammatory bowel disease (IBD). METHODS: C57BL/6 and Lacc1-/- mice were used to establish a mouse model of IBD induced by dextran sodium sulfate (DSS). The effects of Lacc1 deletion in mice were evaluated. Changes in the body weight and stool blood were recorded daily. After 7 days of successful modeling, the mice were sacrificed, blood was collected from the eyeballs, the entire colon was dissected and separated, and the length of the colon was measured. RESULTS: Compared with the wild-type (WT) DSS model group, the Lacc1-/- DSS model group showed a significantly higher disease activity index score (P < 0.05), significantly faster weight loss (P < 0.05), and a significantly shorter colon (P < 0.05), indicating that the colonic mucosal tissue was seriously damaged in the Lacc1-/- DSS model group (P < 0.05). Serum IL-1ß, IL-6, TNF-α, and IFN-γ levels were significantly higher in the Lacc1-/- DSS model group than the WT DSS model group. Principal coordinate analysis showed that there were significant microbiome differences between the WT, Lacc1-/-, WT DSS model, and Lacc1-/- DSS model groups (P < 0.05). Linear discriminant analysis effect size analysis showed that under natural conditions, Lacc1-/- mice had significant changes in their intestinal flora compared with control mice (LDA value > 3 or < 3, P < 0.05). CONCLUSIONS: Lacc1 deletion aggravates DSS-induced IBD in mice.

Effects of underwater swing nodes on water-to-air visible light communication.

In water-to-air visible light communication (W2A-VLC), the dynamics of underwater nodes and a wavy water surface should not be neglected. This paper investigates the link performance by combining the dynamic effects of an underwater light-emitting diode (LED) transmitter with a wavy water surface. Monte Carlo simulation is first adopted to evaluate the underwater LED dynamics. Experimental tests are then conducted to measure and analyze the influence of underwater dynamic parameters on link performance, which shows results consistent with theoretical prediction. It is demonstrated that the swing angle dominates the stability and reliability of the W2A-VLC link under a dynamic water surface, providing some insight into the design of underwater optical transmitters.

Wide dynamic range signal detection for underwater optical wireless communication using a PMT detector.

In the underwater optical wireless communication (UOWC) scenario, a photomultiplier tube (PMT) with higher sensitivity, lower noise, and a larger receiver area is employed as the photon detector to further extend the transmission distance. Due to the complex underwater environment, the high directionality of the light beam, and the vibration of a transceiver, the incident optical power usually spans a very wide dynamic range, and the PMT may operate in any one of the three regimes: pulse, transition, and waveform. While it is difficult to obtain the analytical characterization of the output electric signals across these regimes, this paper resorts to experimental measurements of the upsampled discrete samples within a training symbol duration. Among different statistical distribution fitting options, generalized extreme value (GEV) distribution is found to show excellent performance in fitting the probability density function (PDF) of either multiple samples or the superimposition of all samples within a symbol duration. Then joint sample distribution (JSD) based and superimposed sample distribution (SSD) based symbol detection methods are proposed by adopting the GEV distribution and log-likelihood ratio (LLR) testing criterion. The proposed methods are experimentally evaluated under different received signal optical powers, data rates, and sampling rates. They are shown to outperform the Poisson and Gaussian based maximum likelihood detection methods which are employed for the pulse regime and waveform regime respectively. Furthermore, the effectiveness of the proposed methods in alleviating strong ambient radiation is experimentally verified.

Ultraviolet communication with a large scattering angle via artificial agglomerate fog.

Considering strong signal attenuation of the large-angle non-line-of-sight (NLOS) link achieved due to the ultraviolet (UV) scattering properties, we propose to increase the UV communication link gain under a large scattering angle via generating agglomerate fog within a certain range as a secondary light source. In this study, a channel model with locally strong scatterers from agglomerate fog is proposed based on Monte Carlo ray-tracing approaches. Mie theory is adopted to calculate the atmospheric channel parameters, to further evaluate the link gain of a channel under non-uniform atmosphere. The performance of scattering system in the presence of fog conditions depends on the relative positions of the light source to the fog and to the receiver. The link gain results reveal the transmission capabilities for different scattering channel geometries, and give the optimal spray point location within a 10 m communication range. We further establish a foggy NLOS system using an agglomerate fog generator to verify our research in the real environment. The results show that the received signal strength of the NLOS link can be effectively enhanced by constructing scatterers in the atmospheric channel, which significantly decreases the bit-error rate (BER).

266 nm ultraviolet communication under unknown interference using UVC micro-LED.

Ultraviolet C (UVC) micro light-emitting diode (LED) can achieve symbol communication rate up to 100Msps at distance 40 meters without transmitter-side lens to guarantee certain communication mobility. We consider what we believe to be a new scenario where high speed UV communciation is realized under unknown low-rate interference. The signal amplitude properties are characterized, and the interference intensity is categorized into three cases, namely weak, medium and high interference intensity. The achievable transmission rates for the three cases are derived, where the achievable transmission rate for medium interference intensity can approach those in weak interference intensity and strong interference intensity cases. We provide Gaussian approximation and related log-likelihood ratio (LLR) calculation, which are fed into the subsequent message-passing decoder. In the experiment, the data is transmitted with symbol rate 20 Msps under unknown interference with symbol rate 1 Msps, received by one photomultiplier tube (PMT). Experimental results show that the proposed interference symbol estimation approach shows negligibly higher bit error rate (BER) compared with those with perfect knowledge on the interference symbols.

Pathological response and prognostic factors of neoadjuvant PD-1 blockade combined with chemotherapy in resectable oesophageal squamous cell carcinoma.

PURPOSE: We aimed to investigate the pathological changes, clinicopathological correlation and prognostic factors of neoadjuvant programmed cell death 1 (PD-1) blockade camrelizumab combined with carboplatin and nab-paclitaxel (CCNP) which we have proved its effectiveness in previous research for resectable esophageal squamous cell carcinoma (ESCC). METHODS: 108 patients of resectable ESCC, with a mean follow-up of 13 m (ranging 1-30 m), treated with neoadjuvant CCNP from March 2020 to October 2022 in the First Affiliated Hospital of Sun Yat-sen University were enrolled. RESULTS: One year overall survival (OS) and disease-free survival (DFS) were 96.4% and 84.7% respectively. Pathological complete response or major pathological response (pCR/MPR) of the primary tumour (T-pCR/T-MPR) and the metastatic lymph node (N-pCR/N-MPR) were 58.3% and 47.5%. Pathological response of both primary tumours (PT) and lymph nodes (LN) metastasis correlated with DFS. LN pathological response was consistent with PT in 70.0% and inconsistent in 30.0% metastatic cases. Higher ratio of CD8+ to FoxP3+ tumour-infiltrating lymphocytes (TILs), earlier ypT stage and PT invasion not beyond circular muscle correlated with better pathological response. Four types of regression patterns of PT and two types of metastatic LN regression were found. A total of 18 (16.7%) out of 108 developed recurrence with a mean time of 6.9 ± 5.3 months. PT pathological response plus ypN and PT invasion beyond circular muscle or not were independent prognostic factors of DFS. CONCLUSIONS: This study suggested that camrelizumab plus chemotherapy had a high rate of T-pCR/T-MPR for resectable ESCC. T-pCR/T-MPR plus ypN0 and tumour invasion not beyond circular muscle predicted better DFS.

Multilevel polarization shift keying modulation for turbulence-robust underwater optical wireless communication.

Turbulence is an intractable issue for underwater optical wireless communication (UOWC). Most literature has been mainly focused on the modeling of turbulence channels and performance analysis rather than mitigation of the turbulence effect, especially from the experimental aspects. In this paper, a multilevel polarization shift keying (PolSK) modulation based UOWC system is established utilizing a 15 m-long water tank, and the system performance is investigated under specific temperature gradient-induced turbulence and various transmitted optical powers. Experimental results show the feasibility of the PolSK in alleviating the effect of turbulence, and the bit error rate performance significantly outperforms traditional intensity-based modulation schemes which have difficulty in obtaining an optimal decision threshold in a turbulence channel.

Anti error and erasure coding for water-to-air visible light communication through wavy water surface with wave height up to 0.6 meters.

Considering large dynamic optical intensity range in a water-to-air (W2A) channel, we propose two promising channel coding schemes, namely the concatenated Reed Solomon-Low Density Parity Check (RS-LDPC) code and Raptor code, for W2A visible light communication (VLC). We establish a W2A-VLC link to verify the performance under different wavy water environments and different water depths with a green light emitting diode (LED). A wave generator is adopted to emulate the wavy water surface with wave height up to 0.6 m. The receiver is fixed 3.2 m above the water, and the transmitter varies from 2.5 m to 4.0 m under the water through a up-down-moveable platform. We test the coding schemes with different code lengths and code rates under 5 MSym/s air-interface symbol rate. Experimental results show that both schemes can reduce the bit error ratio (BER) and frame error rate (FER) of a W2A-VLC system, and thus can improve the reliability. Via comparing the two codes with the same overhead and approximately the same code length, it is demonstrated that Raptor code can generally outperform the concatenated RS-LDPC code. Our research provides promising channel coding methods without feedback for a W2A-VLC system.

Bi-directional ultra-violet communication with self-interference.

We investigate the self-interference characterization, achievable rate, signal detection and parameter estimation for bi-directional ultra-violet (UV) communication. We firstly characterize and experimentally demonstrate the self-interference of UV communication, which is non-negligible as the angle between the transmission and receiver directions is blow 60°. Then, we present the achievable rate and symbol detection under self-interference, which show that the offset between self-interference and desirable symbols can increase the achievable rate and decrease the symbol detection error probability. We propose the practical system design with parameter estimation under self-interference. Finally, we experimentally evaluate the receiver-side signal detection with self-interference generated by Field Programmable Gate Array, and the signal detection of a real bidirectional UV communication system. Lower symbol detection error probability can also be observed as the offset between desirable symbols and self-interference symbols increases to half-symbol length from both system-level simulation and real experiments, which further validates the theoretical results.

Weak signal detection for visible light communication in the pulse and transition regimes of an operational PMT detector via an SVM-based learning method.

Photo-multiplier tube can be adopted for optical signal detection under weak signal and ambient light intensity, where the signals can be classified into three regimes, discrete-pulse regime, continuous waveform regime and the transition regime between the discrete-photon and continuous waveform regimes. While Poisson and Gaussian distributions can well characterize the discrete-photon and continuous waveform regimes, respectively, a statistical characterization and the related signal detection in the transition regime are difficult. In this work, we resort to a learning approach for the signal characterization and detection under pulse and transition regimes. We propose a support vector machine (SVM)-based approach for signal detection, which extracts eight key features on the received signal. We optimize the hyper-parameters to improve the SVM detection performance. The proposed SVM-based approach is experimentally evaluated under different symbol and sampling rates, and outperforms that of various statistics-based comparison benchmarks.

DIA-TTS: Deep-Inherited Attention-Based Text-to-Speech Synthesizer.

Text-to-speech (TTS) synthesizers have been widely used as a vital assistive tool in various fields. Traditional sequence-to-sequence (seq2seq) TTS such as Tacotron2 uses a single soft attention mechanism for encoder and decoder alignment tasks, which is the biggest shortcoming that incorrectly or repeatedly generates words when dealing with long sentences. It may also generate sentences with run-on and wrong breaks regardless of punctuation marks, which causes the synthesized waveform to lack emotion and sound unnatural. In this paper, we propose an end-to-end neural generative TTS model that is based on the deep-inherited attention (DIA) mechanism along with an adjustable local-sensitive factor (LSF). The inheritance mechanism allows multiple iterations of the DIA by sharing the same training parameter, which tightens the token-frame correlation, as well as fastens the alignment process. In addition, LSF is adopted to enhance the context connection by expanding the DIA concentration region. In addition, a multi-RNN block is used in the decoder for better acoustic feature extraction and generation. Hidden-state information driven from the multi-RNN layers is utilized for attention alignment. The collaborative work of the DIA and multi-RNN layers contributes to outperformance in the high-quality prediction of the phrase breaks of the synthesized speech. We used WaveGlow as a vocoder for real-time, human-like audio synthesis. Human subjective experiments show that the DIA-TTS achieved a mean opinion score (MOS) of 4.48 in terms of naturalness. Ablation studies further prove the superiority of the DIA mechanism for the enhancement of phrase breaks and attention robustness.

A Novel Technique for Treating Early Deep Surgical Site Infection After Posterior Lumbar Fusion with Instrumentation.

OBJECTIVE: To introduce a novel technique of using incisional vacuum-assisted closure (VAC) after 1-stage incision suture combined with closed suction irrigation system (CSIS) for treating early deep surgical site infection (SSI) after posterior lumbar fusion with instrumentation and to compare it with traditional CSIS. METHODS: This was a retrospective study. Patients with early deep SSI after posterior lumbar fusion with instrumentation from January 2013 to May 2020 who were treated by meticulous debridement followed by either CSIS or incisional VAC after 1-stage incision suture combined with CSIS were identified. The demographic characteristics, treatment features, and outcomes were analyzed and compared between the 2 treatment methods. RESULTS: A total of 48 patients (48/5016, 0.96%) developed early deep SSI, 46 of whom were enrolled in this study. This included 24 patients in the CSIS group (group 1) and 22 patients in the incisional VAC after 1-stage incision suture combined with CSIS group (group 2). All patients received follow-up, with an average of 19.7 months (range, 13-30 months). There were no significant differences in demographic characteristics in both groups (P > 0.05). The number of VAC foam dressing or ordinary dressing changes (P < 0.001), number of debridements (P = 0.028), intravenous antibiotic duration (P = 0.042), oral antibiotic duration (P = 0.019), and hospital stay (P = 0.029) in group 1 were significantly higher than those in group 2. The irrigation duration in group 1 was significantly shorter than that in group 2 (P = 0.007). All patients were eventually cured with satisfactory outcomes. CONCLUSIONS: Compared with CSIS, incisional VAC after 1-stage incision suture combined with CSIS may be recommended considering that it has fewer dressing changes, fewer debridements, longer irrigation duration, shorter duration of antibiotic use, shorter hospital stay, and more convenient nursing care.

Risk Factors for Increased Surgical Drain Output After Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: To investigate the risk factors for increased surgical drain output after transforaminal lumbar interbody fusion (TLIF). METHODS: Patients who underwent TLIF in a single center from June 2017 to January 2020 were included in this study. They were divided into the increased surgical drain output group and no increased surgical drain output group according to the boundary of the median drain output. Patients' demographic and clinical parameters were compared between the 2 groups. Risk factors for increased surgical drain output were identified by univariate and multivariate logistic regression analysis. RESULTS: This study enrolled 368 patients who underwent TLIF. Among them, 187 patients had increased surgical drain output (drain output ≥50th percentile or 480 mL). Univariate analysis showed that age (P < 0.001), smoking status (P = 0.002), number of fused levels (P < 0.001), intraoperative blood loss (P < 0.001), intraoperative end plate injury (P < 0.001), administration of tranexamic acid (TXA) (P = 0.002), and surgical duration (P < 0.001) were significantly associated with increased surgical drain output. Multiple logistic regression analysis revealed that older age (P = 0.001), smoking (P = 0.005), more fused levels (P < 0.001), and intraoperative end plate injury (P = 0.017) were the independent risk factors, while administration of TXA (P = 0.012) was a protective factor. CONCLUSIONS: This study showed that older age, smoking, more fused levels, and intraoperative end plate injury were the independent risk factors, while administration of TXA was a protective factor for increased surgical drain output after TLIF.

Experimental underwater quantum key distribution.

In recent years, the feasibility of quantum key distribution (QKD) in a water channel has been verified by theory and experiment. Here, we present an experimental investigation of QKD and decoy-state QKD based on the BB84 protocol. The experiment was carried out in a 10 m water tank. The attenuation coefficient of tap water is 0.08/m, which is close to Jerlov Type II seawater. We measured the probability-of-detection matrix of polarization states, and the average fidelity of the four polarization states is up to 98.39%. For the 10 m underwater QKD experiment, 20 MHz optical pulses are generated by modulating the laser diode (LD) and attenuated to an average of 0.1 photons per pulse. The security key rate can reach 563.41 kbits/s and the quantum bit error rate (QBER) is 0.36%. Two decoy states (one of which is the vacuum state) was used in the 10 m underwater decoy-state QKD experiment, and the average QBER of signal state is 0.95%, the security key rate reaches 711.29 kbits/s. According to the parameters of the decoy-state experiment, the maximum secure transmission distance of the underwater decoy-state QKD is predicted to be 19.2 m, while it can be increased to 237.1 m in Jerlov Type I seawater with a lower dark count single photon detector (SPD).