The Born in Guangzhou Cohort Study enables generational genetic discoveries.

Genomic research that targets large-scale, prospective birth cohorts constitutes an essential strategy for understanding the influence of genetics and environment on human health1. Nonetheless, such studies remain scarce, particularly in Asia. Here we present the phase I genome study of the Born in Guangzhou Cohort Study2 (BIGCS), which encompasses the sequencing and analysis of 4,053 Chinese individuals, primarily composed of trios or mother-infant duos residing in South China. Our analysis reveals novel genetic variants, a high-quality reference panel, and fine-scale local genetic structure within BIGCS. Notably, we identify previously unreported East Asian-specific genetic associations with maternal total bile acid, gestational weight gain and infant cord blood traits. Additionally, we observe prevalent age-specific genetic effects on lipid levels in mothers and infants. In an exploratory intergenerational Mendelian randomization analysis, we estimate the maternal putatively causal and fetal genetic effects of seven adult phenotypes on seven fetal growth-related measurements. These findings illuminate the genetic links between maternal and early-life traits in an East Asian population and lay the groundwork for future research into the intricate interplay of genetics, intrauterine exposures and early-life experiences in shaping long-term health.

Exosome-transmitted FOSL1 from cancer-associated fibroblasts drives colorectal cancer stemness and chemo-resistance through transcriptionally activating ITGB4.

Cancer-associated fibroblasts (CAFs) have been proved to facilitate colorectal cancer (CRC) development, either with boosting chemo-resistance by communicating with CRC cells in the tumor microenvironment. However, the underlying molecular mechanisms remain largely unclear. Relative expressions of FOSL1 and ITGB4, either with their correlations in CRC tissues, were assessed using qRT-PCR analysis. Also, Kaplan-Meier survival analysis was employed for evaluating the prognosis. Identification of CAFs was determined by the detection of specific makers (α-SMA, FAP, and FSP1) using western blot and immunofluorescence staining. Cell proliferation, self-renewal capacity, and cell apoptosis were estimated by CCK-8, sphere-formation, and flow cytometry assays. Transcriptional regulation of FOSL1 on integrin ß4 (ITGB4) was confirmed using ChIP and dual-luciferase reporter assays. Increased FOSL1 and ITGB4 in CRC tissues were both positively correlated with the poor prognosis of CRC patients. Interestingly, FOSL1 was enriched in the CAFs isolated from CRC stroma, instead of ITGB4. CRC cells under a co-culture system with CAFs-conditioned medium (CAFs-CM) exhibited increased FOSL1, promotive cell proliferation, and reduced apoptosis, while these effects could be blocked by exosome inhibitor (GW4869). Moreover, CAFs-derived exosomal FOSL1 was validated to enhance proliferative ability and oxaliplatin resistance of CRC cells. Our results uncovered that CAFs-derived exosomes could transfer FOSL1 to CRC cells, thereby promoting CRC cell proliferation, stemness, and oxaliplatin resistance by transcriptionally activating ITGB4.

Effects of the quorum sensing related luxS gene and lsr operon on Klebsiella michiganensis resisting copper stress.

Industrial wastewater is a major environmental concern due to its high copper content, which poses significant toxicity to microbial life. Autoinducer-2 (AI-2) can participate in the inter- and intra-species communication and regulate the physiological functions of different bacterial species by producing AI-2 signal molecules. However, there are few research reports on the luxS gene and lsr operon functions for AI-2 in bacteria with a certain tolerance to copper. This study delves into the potential of quorum sensing mechanisms, particularly the AI-2 system, for enhancing microbial resistance to copper toxicity in Klebsiella michiganensis (KM). We detail the critical roles of the luxS gene in AI-2 synthesis and the lsr operon in AI-2 uptake, demonstrating their collective impact on enhancing copper resistance. Our findings show that mutations in the lsr operon, alongside the knockout of the luxS gene in KM strain (KMΔluxSΔlsr), significantly impair the strain's motility (p < 0.0001) and biofilm formation (p < 0.01), underscoring the operon's role in AI-2 transport. These genetic insights are pivotal for developing bioremediation strategies aimed at mitigating copper pollution in wastewater. By elucidating the mechanisms through which KM modulates copper resistance, this study highlights the broader ecological significance of leveraging microbial quorum sensing pathways for sustainable wastewater management.

Information security scheme using deep learning-assisted single-pixel imaging and orthogonal coding.

Providing secure and efficient transmission for multiple optical images has been an important issue in the field of information security. Here we present a hybrid image compression, encryption and reconstruction scheme based on deep learning-assisted single-pixel imaging (SPI) and orthogonal coding. In the optical SPI-based encryption, two-dimensional images are encrypted into one-dimensional bucket signals, which will be further compressed by a binarization operation. By overlaying orthogonal coding on the compressed signals, we obtain the ciphertext that allows multiple users to access with the same privileges. The ciphertext can be decoded back to the binarized bucket signals with the help of orthogonal keys. To enhance reconstruction efficiency and quality, a deep learning framework based on DenseNet is employed to retrieve the original optical images. Numerical and experimental results have been presented to verify the feasibility and effectiveness of the proposed scheme.

Speckle-based optical encryption with complex-amplitude coding and deep learning.

We propose a speckle-based optical encryption scheme by using complex-amplitude coding and deep learning, which enables the encryption and decryption of complex-amplitude plaintext containing both amplitude and phase images. During encryption, the amplitude and phase images are modulated using a superpixel-based coding technique and feded into a digital micromirror device. After passing through a 4f system, the information undergoes disturbance modulation by a scattering medium, resulting in a diffracted speckle pattern serving as the ciphertext. A Y-shaped convolutional network (Y-Net) model is constructed to establish the mapping relationship between the complex-amplitude plaintext and ciphertext through training. During decryption, the Y-Net model is utilized to quickly extract high-quality amplitude and phase images from the ciphertext. Experimental results verify the feasibility and effectiveness of our proposed method, demonstrating that the potential of integrating speckle encryption and deep learning for optical complex-amplitude encryption.

Development and validation of a risk prediction model for the recurrence of foot ulcer in type 2 diabetes in China: A longitudinal cohort study based on a systematic review and meta-analysis.

AIMS: To develop and validate a risk prediction model for Chinese patients with type 2 diabetes with the recurrence of diabetic foot ulcers (DFUs) based on a systematic review and meta-analysis. METHODS: A prospective analysis was performed with 1333 participants and followed up for 60 months. Three models were analysed using a derived cohort. The risk factors were screened using meta-analysis and logistic regression, and the missing variables were interpolated by multiple imputation. The internal validation was performed using the bootstrap procedure, and the validation cohort was applied to the external validation. The performance of the model was evaluated in the area under the discrimination Receiver Operating Characteristic Curve (ROC). Calibration and discrimination methods were used for the validation cohort. The variables were selected according to their clinical and statistical importance to construct the nomograms. RESULTS: Three models were developed and validated. Model 1 included seven social and clinical indicators like sex, diabetes mellitus duration, previous DFU, location of ulcer, smoking, history of amputation, and foot deformity. Model 2 included four more indicators besides those in Model 1, which were statin agents used, antiplatelet agents used, systolic blood pressure, and body mass index. Model 3 added further laboratory indicators to Model 2, such as LDL-C, HbA1C, fibrinogen, and blood urea nitrogen. In the derivation cohort, 20.1% (206/1027) participants with DFU recurred as compared to the validation cohort, which was 38.2% (117/306). The areas under the curve in the derivation cohort for Models 1-3 were 0.781 (0.744-0.817), 0.843 (0.813-0.873), and 0.899 (0.876-0.922), respectively. The Youden indexes for Models 1-3 were 0.430, 0.559, and 0.653, respectively. Model 3 showed the highest sensitivity and specificity. All models performed well for both discrimination and calibration. CONCLUSIONS: Models 1-2 were non-invasive, which indicate their role in general screening for patients at a high risk of recurrence of DFU. However, Model 3 offers a more specific screening due to its best performance in predicting the risk of DFU recurrence amongst the three models.

Formation ability and drug resistance mechanism of Klebsiella pneumoniae biofilm and capsule for multidrug-resistant.

This study was to explore the formation ability of biofilm and capsule and the drug resistance mechanism for multidrug-resistant Klebsiella pneumoniae. firstly, 55 strains of K. pneumoniae were screened out from the body fluid specimens of the laboratory. The strains were drug-resistant, and the characteristics of clinical infections of these strains were analyzed. Secondly, all strains were tested for the presence of biofilms and capsules, and then the deoxyribonucleic acid (DNA) genomes of the strains extracted were detected using polymerase chain reaction (PCR) technology. Finally, the serotype genes and virulence genes of the strains were screened, and the relationship between these two genes and the formation of capsules and biofilms was analyzed and compared. A new generation of sequencing technology was applied to analyze the genome structure of K. pneumoniae, comparative genomics technology was adopted to analyze the drug resistance plasmids, and molecular cloning and other methods were utilized to clone the drug resistance-related genes. of the 55 strains of K. pneumoniae isolated clinically, 61.8% came from blood with a total number of 34 strains; 8 strains were from secretion specimens (accounting for 14.5% of the total); and 7 strains were from drainage fluid (accounting for 12.7% of the total), including 2 strains from pus, bile, and pleural fluid, respectively. The strains were tested by PCR, of which iroN virulence genes were the most (34 strains), accounting for 61.8%, followed by wabG and fimH (33 strains, accounting for 60% of the total), followed by magA, K2, K20, K1, and K57. The positive rates of the two virulence genes (fimH and wabG) were higher in positive strains of biofilm. The drug susceptibility results showed that ampicillin and amoxicillin were more resistant to capsule-positive strains than the capsule-negative strains. K. pneumoniae had been able to form a complete capsule and biofilm, the formation rate of biofilm was higher than that of the capsule, and there was an increasing trend. The two serotype genes (K20 and K2) accounted for relatively high proportions, and K. pneumoniae carried relatively more virulence genes (wabG and fimH), which may be closely related to the capsule production of K. pneumoniae. In addition, resistance-related genes were also transferred horizontally in different strains of bacteria, forming a wide range of drug resistance, which brought great difficulties to clinical work.

Chinese patent medicines for coronary microvascular disease: clinical evidence and potential mechanisms.

Coronary microvascular disease (CMVD) is a high risk factor for many cardiovascular events. Due to the limited understanding of its pathophysiological mechanism, modern medicine still lacks therapeutic drugs for CMVD. Existing clinical studies have shown that traditional Chinese medicine (TCM) can effectively improve the clinical symptoms and quality of life of CMVD patients. As an indispensable part of TCM, Chinese patent medicines (CPMs) are widely used in clinical practice. In the face of numerous oral CPMs for treatment of CMVD, how to choose a reasonable medication regimen is one of the important issues in clinic. Based on this, this paper reviewed the clinical efficacy and recommended level of 12 CPMs in the treatment of CMVD, which are recommended by expert consensus on diagnosis and treatment of coronary microvascular disease with integrated Chinese and Western medicine (WM). In addition, this study also systematically summarized the possible mechanisms of CPMs in the treatment of CMVD by protecting coronary microvascular endothelial cells, improving vascular endothelial function, inhibiting inflammation, reducing oxidative stress, promoting angiogenesis, and improving hemorheology, aiming to provide meaningful information for its clinical application.

Incremental predictive value of platelet parameters for preeclampsia: results from a large prospective cohort study.

BACKGROUND: Platelet parameters during pregnancy were associated with the risk of preeclampsia (PE), but the predictive value of these parameters for PE remained unclear. Our aim was to clarify the individual and incremental predictive value of platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) for PE. METHODS: This study was based on the Born in Guangzhou Cohort Study in China. Data on platelet parameters were extracted from medical records of routine prenatal examinations. Receiver operating characteristic (ROC) curve was performed to analyze the predictive ability of platelet parameters for PE. Maternal characteristic factors proposed by NICE and ACOG were used to develop the base model. Detection rate (DR), integrated discrimination improvement (IDI) and continuous net reclassification improvement (NRI) were calculated compared with the base model to assess the incremental predictive value of platelet parameters. RESULTS: A total of 30,401 pregnancies were included in this study, of which 376 (1.24%) were diagnosed with PE. Higher levels of PC and PCT were observed at 12-19 gestational weeks in women who developed PE later. However, no platelet parameters before 20 weeks of gestation reliably distinguished between PE complicated pregnancy and non-PE complicated pregnancy, with all values of the areas under the ROC curves (AUC) below 0.70. The addition of platelet parameters at 16-19 gestational weeks to the base model increased the DR for preterm PE from 22.9 to 31.4% at a fixed false positive rate of 5%, improved the AUC from 0.775 to 0.849 (p = 0.015), and yielded a NRI of 0.793 (p < 0.001), and an IDI of 0.0069 (p = 0.035). Less but significant improvement in prediction performance was also observed for term PE and total PE when all the four platelet parameters were added to the base model. CONCLUSIONS: Although no single platelet parameter at the early stage of pregnancy identified PE with high accuracy, the addition of platelet parameters to known independent risk factors could improve the prediction of PE.

Steganographic optical image encryption based on single-pixel imaging and an untrained neural network.

We propose a steganographic optical image encryption based on single-pixel imaging (SPI) and an untrained neural network. In this encryption scheme, random binary illumination patterns are projected onto a secret image and light intensities reflected from the image are then detected by a bucket detector (BD). To enhance the security of collected secret data, a steganographic approach is introduced in this method, which implements data hiding with a SPI system using encoded illumination patterns. A non-secret image is illuminated with a sequence of encoded patterns that were generated from the scrambled measurements of secret image, and sequential cyphertext data can be obtained by collecting the diffraction data with the BD. Different from traditional SPI-based encryption schemes, an untrained neural network is adopted as a SPI-encrypted image processor, which allows to reduce time spent on data preparation and reconstruct the secret images with high quality. Both computer simulations and optical experiments are carried out to demonstrate the feasibility of the method.

Synthesis of novel dual target inhibitors of PARP and EGFR and their antitumor activities in triple negative breast cancers.

The therapeutic strategy of poly (ADP-ribose) polymerase (PARP) inhibition of BRCA1/2 mutant cancers has been overwhelmingly successful, however, the highly aggressive triple negative breast cancers (TNBC) that receptor protein tyrosine kinase (RTKs) is known to be overexpressed are not sensitive to PARP inhibitors. Our research focused on exploring PARP inhibitors incorporating a bicyclic tetrahydropyridine pyrimidine. All synthesized compounds were more potent than Olaparib (ola) in killing tumor cells, especially in TNBC. Furthermore, compound 7 exhibited strong inhibitory effects on PARP enzymatic activity, moreover, the expression of EGFR and phosphorylated EGFR was inhibited by compound 7. Therefore, compound 7 can effectively inhibit TNBC cells with high expression of EGFR. In addition, significant synergistic effect of anti-tumor effect of new PARP inhibitors and adriamycin was also observed.

Discovery of CN0 as a novel proteolysis-targeting chimera (PROTAC) degrader of PARP1 that can activate the cGAS/STING immunity pathway combined with daunorubicin.

Poly ADP-ribose polymerase 1 (PARP1) plays an essential role in DNA repair signaling, rendering it an attractive target for cancer treatment. Despite the success of PARP1 inhibitors (PARPis), only a few patients can currently benefit from PARPis. Moreover, drug resistance to PARPis occurs during clinical treatment. Natural and acquired resistance to PARPis has forced us to seek new therapeutic approaches that target PARP1. Here, we synthesized a series of compounds by proteolysis-targeting chimera (PROTAC) technology to directly degrade the PARP1 protein. We found that CN0 (compound 3) with no polyethylene glycol (PEG) linker can degrade the PARP1 protein through the proteasome pathway. More importantly, CN0 could inhibit DNA damage repair, resulting in highly efficient accumulation of cytosolic DNA fragments due to unresolved unrepaired DNA lesions when combined with daunorubicin (DNR). Therefore, CN0 can activate the cyclic GMP-AMP synthase/stimulator of the interferon gene (cGAS/STING) pathway of innate immunity and then spread the resulting inflammatory signals, thereby reshaping the tumor microenvironment, which may eventually enhance T cell killing of tumor cells.

Platelet parameters and risk of hypertension disorders of pregnancy: a propensity score adjusted analysis.

While the role of platelets in cardiovascular diseases among the general population has been widely reported, evidence is inconsistent regarding the association between platelet indices with hypertension in pregnant women. In this study, we explored the associations between platelet parameters before 20 gestational weeks, an understudied period, with hypertensive disorders of pregnancy (HDP), including preeclampsia/eclampsia (PEEC) and gestational hypertension (GH). Based on the Born in Guangzhou Cohort Study, 12053 singleton pregnant women with platelet parameters, including platelet count (PC), mean platelet volume (MPV), plateletcrit (PCT), and platelet distribution width (PDW) measured at 14-19 gestational weeks were included. Conventional multivariable adjustment and propensity score analysis were used to control for confounders. The restricted cubic spline showed that the risk of PEEC increased linearly for PC, and non-linearly for PCT. For GH, the risk increased linearly for PC, MPV, and PCT, and non-linearly for PDW. When these indices were categorized into quintiles, women with higher PC and PCT were associated with increased risk of both PEEC and GH. Women with MPV exceeding the second quintile (≥ 8.8 fL) had a greater risk for GH, but not for PEEC. When HDP was classified into two groups (early- vs late-onset) based on the occurrence time, significant associations persisted for early-onset PEEC, early-onset GH, and late-onset GH. In conclusion, increased PC and PCT before 20 weeks of gestation were both associated with higher risk of PEEC and GH, while elevated MPV was only linked to GH.

Gestational weight gain rates in the first and second trimesters are associated with small for gestational age among underweight women: a prospective birth cohort study.

BACKGROUND: Despite the well-studied effects of gestational weight gain (GWG) on offspring health, little is known about the association of trimester-specific GWG with offspring birth weight among underweight pregnant women. This study aimed to explore the association of trimester-specific GWG rate with small for gestational age (SGA) in underweight women. METHODS: The GWG rate of underweight pregnant women (pre-pregnancy body mass index [BMI] lower than 18.5 kg/m2) of the Born in Guangzhou Cohort Study was calculated as the weight gain during a specific trimester divided by the corresponding duration of week. Total GWG was calculated as the weight difference between pre-pregnancy and delivery, and was categorized into inadequate, adequate, and excessive weight gain based on the 2009 Institute of Medicine (IOM) weight gain recommendation. The INTERGROWTH-21st standards were used to define SGA. Logistic regression models were used to examine the associations of total GWG and trimester-specific GWG rates with SGA. Associations between trimester-specific GWG rates and SGA were also analyzed separately based on different total GWG categories (i.e. inadequate and adequate/excessive GWG). RESULTS: Of the 3839 participants, SGA births occurred in 397 (10.3%), and mean GWG was 14.9 kg (SD 3.9). A lower risk of SGA was observed among women with higher GWG rate (per 0.5 kg/week increase) during the first (adjusted OR [aOR] 0.74, 95%CI 0.57, 0.96) and second (adjusted OR [aOR] 0.40, 95%CI 0.30, 0.55) but not third trimester. Similar association between higher GWG rate during the second trimester and a decreased risk of SGA were observed among women with inadequate (< 12.5 kg) and adequate/excessive (≥12.5 kg) total GWG, respectively. Compared to women with adequate GWG rate, women with inadequate GWG rate during the second trimester had a significantly increased risk of SGA (aOR 1.58, 95% CI 1.14, 2.20). CONCLUSIONS: Second-trimester GWG might be the key driver for the association between inadequate GWG and increased risk of SGA births in underweight women.

Benefits of different combinations of aerobic and resistance exercise for improving plasma glucose and lipid metabolism and sleep quality among elderly patients with metabolic syndrome: a randomized controlled trial.

Exercise has beneficial effects on metabolic syndrome (MS). However, the exercise prescriptions that best support plasma glucose and lipid control remain unknown. We evaluated the effects of different combinations of aerobic and resistance training programs on plasma glucose and lipid metabolism and sleep quality in elderly MS patients. Eighty-five elderly MS patients were randomly assigned to five groups: aerobic training (AT), resistance training (RT), high aerobic with low resistance training (HALRT), high resistance with low aerobic training (HRLAT), or control. The exercise groups performed supervised moderate-intensity exercise during three 50-min sessions per week for 12 weeks. Body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), handgrip strength (HGS), fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels and sleep quality were evaluated at baseline and after 12 weeks. All intervention groups showed significant improvements in SBP, HGS, FPG, 2hPG, and Pittsburgh Sleep Quality Index (PSQI) scores compared to baseline (all p < 0.05), while DBP, TC, TG, and LDL-C levels were significantly improved only in the HRLAT and HALRT groups (p < 0.05). The HALRT group showed the largest improvements in WC, SBP, DBP, HGS, FPG, 2hPG, and PSQI score (p < 0.001). The largest improvements in BMI, TC, and LDL-C were observed in the HRLAT group (p < 0.001). The combined exercise prescriptions were more effective than aerobic or resistance training alone at improving plasma glucose and lipid metabolism and sleep quality in elderly MS patients.

[Network Meta-analysis of efficacy and safety of oral Chinese patent medicines combined with conventional western medicine in treatment of hypertension].

This study aims to systematically evaluate the effect of oral Chinese patent medicines on hypertension with network Meta-analysis. Randomized controlled trials on the treatment of hypertension with oral Chinese patent medicine combined with conventional western medicine were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library(from establishment of the database to August 2021). Two researchers independently screened the articles, extracted the data, and evaluated article quality. Then R 4.1.0 was employed for data analysis. Finally, 195 eligible articles were screened out, involving 22 546 patients and 18 oral Chinese patent medicines. The results of the network Meta-analysis are as follows. In terms of reducing systolic blood pressure(SBP) and diastolic blood pressure(DBP), Xuesaitong, Qiangli Dingxuan Tablets, Songling Xuemaikang Capsules combined with conventional western medicine are superior. In improving blood lipids, the overall effects of Xinmaitong Capsules, Compound Xueshuantong Capsules, Ginkgo Folium preparations, Yindan Xinnaotong Soft Capsules, and Naoxintong Capsules combined with conventional western medicine are outstanding. In terms of regulating endothelial function, Yindan Xinnaotong Soft Capsules, Xinmaitong Capsules, Zhenju Jiangya Tablets, Compound Danshen Dripping Pills, Xuesaitong with conventional western medicine have certain advantages. As for the safety, the incidence of adverse reactions of conventional western medicine combined with oral Chinese patent medicines is lower than that of conventional western medicine alone. In summary, compared with conventional western medicine alone, the 18 oral Chinese patent medicines combined with conventional western medicine in the treatment of hypertension show advantages in improving blood pressure, blood lipids, and endothelial function. Among them, Xuesaitong, Qiangli Dingxuan Tablets, and Songling Xuemaikang Capsules may be the best oral Chinese patent medicines for lowering blood pressure. The conclusion needs to be further verified by more high-quality studies.

An acute decrease in plasma membrane tension induces macropinocytosis via PLD2 activation.

Internalization of macromolecules and membrane into cells through endocytosis is critical for cellular growth, signaling and plasma membrane (PM) tension homeostasis. Although endocytosis is responsive to both biochemical and physical stimuli, how physical cues modulate endocytic pathways is less understood. Contrary to the accumulating discoveries on the effects of increased PM tension on endocytosis, less is known about how a decrease of PM tension impacts on membrane trafficking. Here, we reveal that an acute decrease of PM tension results in phosphatidic acid (PA) production, F-actin and phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2]-enriched dorsal membrane ruffling and subsequent macropinocytosis in myoblasts. The PA production induced by decreased PM tension depends on phospholipase D2 (PLD2) activation via PLD2 nanodomain disintegration. Furthermore, the 'decreased PM tension-PLD2-macropinocytosis' pathway is prominent in myotubes, reflecting a potential mechanism of PM tension homeostasis upon intensive muscle stretching and relaxation. Together, we identify a new mechanotransduction pathway that converts an acute decrease in PM tension into PA production and then initiates macropinocytosis via actin and PI(4,5)P2-mediated processes.

Effect of real-time ultrasound imaging for biofeedback on trunk muscle contraction in healthy subjects: a preliminary study.

BACKGROUND: Real-time ultrasound imaging (RUSI) has been increasingly used as a form of biofeedback when instructing and re-training muscle contraction. However, the effectiveness of the RUSI on a single sustained contraction of the lumbar multifidus (LM) and transversus abdominis (TrA) has rarely been reported. This preliminary study aimed to determine if the use of RUSI, as visual biofeedback, could enhance the ability of activation and continuous contraction of the trunk muscles including LM and TrA. METHODS: Forty healthy individuals were included and randomly assigned into the experimental group and control group. All subjects performed a preferential activation of the LM and/or TrA (maintained the constraction of LM and/or TrA for 30 s and then relaxed for 2 min), while those in the experimental group also received visual feedback provided by RUSI. The thickness of LM and/or TrA at rest and during contraction (Tc-max, T15s, and T30s) were extracted and recorded. The experiment was repeated three times. RESULTS: No significant differences were found in the thickness of LM at rest (P > 0.999), Tc-max (P > 0.999), and T15s (P = 0.414) between the two groups. However, the ability to recruit LM muscle contraction differed between groups at T30s (P = 0.006), with subjects in the experimental group that received visual ultrasound biofeedback maintaining a relative maximum contraction. Besides, no significant differences were found in the TrA muscle thickness at rest (P > 0.999) and Tc-max (P > 0.999) between the two groups. However, significant differences of contraction thickness were found at T15s (P = 0.031) and T30s (P = 0.010) between the two groups during the Abdominal Drawing-in Maneuver (ADIM), with greater TrA muscle contraction thickness in the experimental group. CONCLUSIONS: RUSI can be used to provide visual biofeedback, which can promote continuous contraction, and improve the ability to activate the LM and TrA muscles in healthy subjects.

Transcriptomic analysis reveals resistance mechanisms of Klebsiella michiganensis to copper toxicity under acidic conditions.

The aim of this study was to elucidate the effect of pH on bacterial resistance mechanisms to copper (Cu) stress by genomic and transcriptomic analysis. Klebsiella michiganensis cells were exposed to 0.5 mM CuCl2 at pH 4 and 5. Lower pH (pH < 4) strongly inhibited K. michiganensis growth, while Cu stress and higher pH (pH > 5) induced Cu precipitation in the medium. Transcriptomic analyses indicated that two groups of genes related to quorum sensing (QS) systems (lsrABCDFGKR) and type II secretion systems (T2SS) (gspCDEFGHIJKLM) were significantly up-regulated at pH 4 only. These results suggest that T2SS may be induced and controlled by QS, thereby contributing to the formation of extracellular polymeric substances (EPS) and the secretion of proteins to prevent Cu ions from entering cells. Six Cu resistance genes (cusABF, copA, cueO, and gene05308) were more significantly up-regulated at pH 4 than at pH 5. In addition, the relative expression (log2|FC=) of the sulfur assimilation genes cysHJIK was relatively higher at pH 4 than at pH 5, while the gene encoding organic sulfur metabolism, tauB, was also significantly up-regulated at only pH 4. These results indicate that the Cu efflux system can remove intracellular Cu ions from cells, and that the sulfur assimilation system is related to the detoxification of Cu ions. Furthermore, increased free Cu ions at lower pH (4) could induce communication signals among cells, thereby stimulating the response of T2SS-related genes in K. michiganensis to tolerate Cu stress. Consequently, the resistance of K. michiganensis to Cu stress is a multisystem collaborative process composed of intracellular and extracellular components.

Capn4 is induced by and required for Epstein-Barr virus latent membrane protein 1 promotion of nasopharyngeal carcinoma metastasis through ERK/AP-1 signaling.

Capn4, also known as CapnS1, is a member of the calpain family, which plays a crucial role in maintaining the activity and function of calpain. We previously reported that Capn4 also plays an essential role in the migration of nasopharyngeal carcinoma (NPC) cells through regulation of (MMP-2) by nuclear factor-kappa B activation. Epstein-Barr virus latent membrane protein 1 (LMP1) is closely related to the malignant functions of NPC; however, the relationship between LMP1 and Capn4 in NPC remain unclear. Immunohistochemical studies showed that the level of LMP1 and Capn4 expression was high in both primary and metastatic NPC tissues, with a significantly positive correlation. We further found that LMP1 was able to upregulate the Capn4 promoter in a dose-dependent way through the C-terminal activation region (CTAR)1 and CTAR2 domains to activate AP-1. Moreover, we also found that LMP1 activated AP-1 through ERK/JNK phosphorylation. These findings indicate that Capn4 coordination with LMP1 promotes actin rearrangement and, ultimately, cellular migration. These results show that Capn4 coordination with LMP1 enhances NPC migration by increasing actin rearrangement involving ERK/JNK/AP-1 signaling. Therapeutically, additional and more specific LMP1 and Capn4 targeted inhibitors could be exploited to treat NPC.