Baduanjin is Better Balance Training Compared to Walking: A Cross-Sectional Study Based on Center of Gravity Trajectories.

BACKGROUND:  It has already been demonstrated by previous studies that Baduanjin training can improve the body's balance. However, its biomechanical mechanism remains unknown. Center of gravity (COG) trajectory analysis is an essential biomechanical test to explore the balance ability of the human body. Previous studies have not used the COG trajectory analysis technique to research Baduanjin training. The study utilizes COG trajectory analysis to analyze the trajectory of COG during Baduanjin training and compare it with that of walking, which is a common exercise for improving balance and aerobic ability, to determine if Baduanjin exercises affect the COG more than walking. MATERIALS AND METHODS:  Eight healthy female college students performed the walking and the eight forms of Baduanjin, a total of nine motions. The lower body kinematics were captured by the Vicon Motion Capture and Analysis System, while the kinetic data were acquired by the Kistler 3D Force Platform. The data were imported into Visual 3D to process the trajectory of the COG displacement amplitude, velocity, and acceleration of each motion. The COG horizontal envelope areas were calculated by Origin 9.0 Software (Origin Lab, Northampton, Massachusetts, USA) . RESULTS: Specific motions of Baduanjin provided significantly higher COG displacement amplitude, velocities, and acceleration training than walking. The F2 and F5 motions could provide a larger COG horizontal envelope area than walking. On the x-axis, F2 provided a greater COG displacement amplitude than walking, F1, F2, and F5 provided greater velocities, while all the motions provided greater accelerations. On the y-axis, all the motions except F2 provided greater COG displacement velocities and accelerations than walking. On the z-axis, F1-7 provided a greater COG displacement amplitude than walking, all the motions provided greater velocities, while all the motions except F2 provided greater accelerations. CONCLUSION: Baduanjin training provides a more intense COG perturbation than walking, which may be a more challenging balance training than walking.

Glaucoma drainage device implantation and cyclophotocoagulation in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty.

AIM: To compare the surgical outcomes of glaucoma drainage device implantation (GDI) and trans-scleral neodymium:YAG cyclophotocoagulation (CPC) in the management of refractory glaucoma after Descemet-stripping automated endothelial keratoplasty (DSAEK). METHODS: This retrospective study on observational case series enrolled 29 patients who underwent DSAEK and posterior anti-glaucoma surgery (15 with GDI and 14 with CPC). The main outcome measures were intraocular pressure (IOP), glaucoma surgery success rate (defined as IOP of 6-21 mm Hg without additional anti-glaucoma operation), number of glaucoma medications, endothelial graft status, and best-corrected visual acuity (BCVA). RESULTS: The mean follow-up time was 34.1 and 21.0mo for DSAEK or glaucoma surgeries, both for the GDI and CPC groups. Both groups showed significant IOP reduction after glaucoma surgery. The GDI group presented a significantly higher success rate in IOP control than the CPC group (60% vs 21.4%, P=0.03). Both procedures significantly decreased the number of glaucoma medications (P=0.03). Forty percent and 57% of cases in the GDI and the CPC group, respectively, experienced endothelial graft failure during follow-up (P=0.36). Significantly worse BCVA after surgery was observed in the CPC group but not in the GDI group. CONCLUSION: Both GDI and CPC significantly decrease IOP in eyes with glaucoma after DSAEK. GDI is preferable to CPC in refractory glaucoma cases after DSAEK, as it manifests a significantly higher success rate for IOP control, similar endothelial graft failure rate, and relatively preserves BCVA than CPC.

Effect of adding hip exercises to general rehabilitation treatment of knee osteoarthritis on patients' physical functions: a randomized clinical trial.

BACKGROUND: Hip adductor and abductor strength were both reduced in KOA patients. But to date, most of the researches have only focused on quadriceps combined with hip abductor strengthening versus quadriceps strengthening. OBJECTIVE: The aim of the study is to evaluate the effect of adding hip abductor and adductor strengthening to quadriceps strengthening on lower limb strength, knee pain and physical function in patients with medial compartmental knee osteoarthritis. METHODS: In this study, 42 participants, were randomly divided into two groups: the general treatment group (GT group) and the added-hip-exercise group (AH group). All participants were given a general rehabilitation treatment. The AH group performed hip abductor and adductor strengthening in addition to the general rehabilitation treatment. Knee and hip muscle strength, Five Times Sit-to-Stand Test (FTSST), the Timed Up and Go Test (TUGT), Numerical Rating Scale (NRS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were assessed at baseline and 6 weeks. A two-sided 2-sample unpaired t test was performed to compare the difference in mean change scores between AH and GT groups. RESULTS: Finally, 36 participants completed the study: both groups consist of 18 participants. In the per-protocol analysis, the AH group had a greater improvement in knee extension strength (mean changes, 7.84 versus 36.48; P < 0.001) and hip abduction strength (mean changes, 5.05 versus 26.62; P = 0.001) than the control group. Similarly, the AH group had a greater improvement in the FTSST time (mean changes, 0.40 s versus 3.57 s; P < 0.001) and the TUFT time (mean changes, 0.18 s versus 1.67 s; P = 0.002) than the GH group. No statistical difference was found in the change of WOMAC pain scores and NRS between the 2 groups. CONCLUSIONS: Older adults with knee OA in the AH group had superior muscle strength, symptoms and daily activity performance at the 6th week than those in the GT group. And adding hip exercises could expedite improvement of pain at the 2th week, but not at the 6th week. TRIAL REGISTRATION: Clinical trial registration numbers and date of registration: ChiCTR-IOR-16009124, Registered 30 August 2016.

Improved long-term outcomes after innovative preoperative evaluation and conception of precise surgery for gallbladder cancer.

BACKGROUND: Three-dimensional visualization preoperative evaluation (3D-VPE) and enhanced recovery after surgery (ERAS) have been suggested to improve outcomes of cancer surgery in patients, yet little is known regarding their clinical benefit in patients with gallbladder cancer (GBC). We hypothesized that the combination of 3D-VPE and ERAS would improve the outcome of patients undergoing surgery for GBC. OBJECTIVE: This study aimed to determine if 3D-VPE and ERAS can improve the outcomes and overall survival in patients with GBC, establishing a novel patient management strategy for GBC. METHODS: A total of 227 patients with GBC were recruited and divided into two groups: those who received traditional treatment between January 2000 and December 2010 (n = 86; the control group) and those who underwent 3D-VPE and ERAS between January 2011 and December 2017 (n = 141). Univariate and multivariate analyses were employed to assess the relationship among disease stages, lymph node invasion, and cell differentiation between the two groups. Cox regression analysis was used to investigate patient survival in these groups. RESULTS: Patients who underwent 3D-VPE and ERAS showed a significantly higher R0 resection rate (67.4% vs. 20.9%, p < 0.001) and dissected lymph node number (26.6 ± 12.6 vs. 16.3 ± 7.6 p < 0.001) compared to the control group. The median survival was 27.4 months, and the 1- and 3-year survival rates were 84.4% and 29.8%, respectively, in patients who received combined management; in the control cohort, the median survival was 12.7 months, and the 1- and 3-year survival rates were 53.5% and 15.1%, respectively. In addition, some postoperative complications and risk factors were diminished relative to the traditionally treated patients. CONCLUSION: The implementation of 3D-VPE and ERAS can significantly improve the prognosis and outcomes of patients with GBC and should be considered for wide use in clinical practice.

Case report: A de novo ERBB3 mutation develops in a gallbladder cancer patient carrying BRCA1 mutation after effective treatment with olaparib.

Background: Gallbladder cancer (GBC) is highly lethal and resistant to most chemotherapeutic drugs. GBC was reported to carry multiple genetic mutations such as TP53, K-RAS, and ERBB2/3. Here, we unexpectedly identified a patient with GBC harboring germline BRCA1 p.Arg1325Lys heterozygous mutation. We sought to determine if olaparib, the poly ADP-ribose polymerase inhibitor (PARPi) commonly treated for BRCA mutation, can inhibit cancer development via a therapeutic trial on this patient. Case presentation: The patient received GBC R0 resection after an 8-week olaparib treatment. After surgery and 6-month follow-up treatment with olaparib, the patient's blood carbohydrate antigen 19-9 (CA19-9) level declined from 328 to 23.6 U/ml. No recurrence in CT scanning was observed, indicating a disease-free survival of 6 months with conventional therapy. Two months later, CT examination and CA19-9 level showed cancer relapse. A blood biopsy revealed a new ERBB3 p.Gly337Arg mutation. GBC cell lines ectopically expressing BRCA1 p.Arg1325Lys together with ERBB3 p.Gly337Arg mutations were challenged with olaparib and/or afatinib, an ERBB2/3 inhibitor. The dual mutation cells were more responsive to the combined olaparib with afatinib than a single drug in the cell proliferation assay. Conclusion: Olaparib is effective in a GBC patient with a BRAC1 mutation. The efficacy of olaparib and afatinib in both cultured BRAC1 and ERBB3 mutation cell lines suggests that a combined regimen targeting BRCA1/2 and ERBB2/3 mutations may be an optimal strategy to treat GBC patients who carry both gene mutations.

Knockdown of Long Noncoding RNA 01124 Inhibits the Malignant Behaviors of Colon Cancer Cells via miR-654-5p/HAX-1.

Background: Previous studies have shown that long noncoding RNAs (lncRNAs) play a key role in cancer, including colon cancer (CC). However, the exact role of long noncoding RNA 01124 (LINC01124) in CC and its mechanisms of action remain unknown. In this study, we investigated the functional effects and the possible mechanism of LINC01124 in CC. Methods: We first determined the expression of LINC01124 in CC tissues (The Cancer Genome Atlas (TCGA) database) and cell lines (quantitative real-time polymerase chain reaction (qRT-PCR)). Functional analysis via Cell Counting Kit-8 (CCK-8), colony formation, cell cycle, wound healing and Transwell assays were performed, and a mechanistic experiment was performed with the western blotting. The function of LINC01124 was also determined in vivo using nude BALB/c mice. Results: The results showed that LINC01124 was upregulated in CC tissues and cell lines. Functional studies showed that knockdown of LINC01124 significantly suppressed the proliferation, migration, and invasion of colon cancer cells in vitro and in vivo. Subsequent mechanistic experiments indicated that LINC01124 acted as a sponge to suppress microRNA 654-5p, which targeted HAX-1. Downregulation of LINC01124 decreased the expression of HAX-1, and overexpression of the miR-654-5p inhibitor attenuated the sh-LINC01124-induced inhibition of CC cell proliferation, migration, and invasion. Conclusion: Collectively, this study revealed that the knockdown of LINC01124 inhibited the malignant behaviors of CC via the miR-654-5p/HAX-1 axis, suggesting that LINC01124 might be a therapeutic target for CC treatment.

Compound Biejia-Ruangan tablet as an adjunctive therapy to entecavir for chronic hepatitis B complicated with hepatic fibrosis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The compound Biejia-Ruangan tablet (CBRT), as an adjunctive therapy to entecavir, is a potential treatment for hepatic fibrosis (HF) in patients with chronic hepatitis B (HBV). However, the present study yielded inconsistent results. In this systematic review and meta-analysis, we comprehensively investigated the efficacy and safety of CBRT as an adjunctive modality to entecavir for the treatment of HBV infection complicated with HF. METHODS: We searched the Cochrane Library, PubMed, Embase, CNKI, VIP, CBM, and Wangfang databases through April 1, 2022, for randomized controlled trials (RCTs) assessing the effect and safety of CBRT as an adjunctive modality to entecavir for HBV complicated with HF. The primary outcomes were biochemical parameters of serum hyaluronic acid, laminin (LN), pretype-III collagen (PC-III), and type IV collagen (IV-C). The secondary outcomes were liver function indices of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBiL) levels, total effect rate, and occurrence rate of adverse events. Two researchers independently conducted study selection, data extraction, and quality assessment. Statistical analysis was performed using the RevMan 5.3 software. RESULTS: Eight RCTs involving 747 patients were included. Compared with entecavir monotherapy, CBRT as an adjunctive therapy to entecavir exerted more encouraging effect in serum levels of hyaluronic acid (mean difference [MD] = -28.15; 95% confidence interval [CI]: -43.82 to -12.47; P < .001), LN (MD = -29.46; 95% CI: -50.69 to -8.23; P < .001), PC-III (MD = -11.83; 95% CI: -19.43 to -4.23; P < .001), and IV-C (MD = -19.62; 95% CI: -29.76 to -9.49; P < .001); levels of serum ALT (MD = -16.83; 95% CI: -26.30 to -7.36; P < .001), AST (MD = -20.52; 95% CI: -33.11 to -7.93; P < .001), and TBiL (MD = -7.54; 95% CI: -11.58 to -3.49; P < .001); and total effect rate (odds ratio = 3.53; 95% CI: 1.71-7.29; P < .001). Meta-analysis results also showed that CBRT as an adjunctive therapy to entecavir had a lower occurrence rate of adverse events (odds ratio = 0.54; 95% CI: 0.22-1.34; P < .001) than entecavir alone. CONCLUSION: The results of this study showed that CBRT as an adjunctive modality to entecavir may benefit HBV patients complicated with HF. High-quality RCTs are needed to confirm the current findings in the future.

Trastuzumab combined chemotherapy for the treatment of HER2-positive advanced gastric cancer: A systematic review and meta-analysis of randomized controlled trial.

BACKGROUND: This systematic review and meta-analysis aimed to assess the efficacy of trastuzumab combined with chemotherapy for the treatment in HER2-positive advanced gastric cancer (HER2-PAGC). METHODS: This systematic review and meta-analysis was designed using randomized controlled trials that compared trastuzumab in combination with chemotherapy and chemotherapy alone. A comprehensive search was conducted in the following databases from their inception onwards: PubMed, EMBASE, Cochrane Library, WANGFANG, and CNKI. We also searched other literature sources to avoid missing relevant studies. Two reviewers independently performed all record selection, data collection, and methodological assessments. Any confusion was resolved by discussion or referral to a third reviewer. If there were ample data from eligible studies, we performed a fixed-effects meta-analysis. Whenever this was not possible, we conducted a narrative synthesis. RESULTS: Meta-analysis results showed that trastuzumab in combination with chemotherapy achieved better outcomes on response rate (trastuzumab plus CFC vs CFC: odds ratio [OR] = 1.56, 95% confidence interval [CI] [1.17-2.09], I2 = 0%, P < .003; trastuzumab plus OT vs OT: OR = 2.97, 95% CI [1.74-5.09], I2 = 0%, P < .0001; and trastuzumab plus CC vs CC: OR = 2.62, 95% CI [1.84-3.73], I2 = 0%, P < .0001), and disease control rate (trastuzumab plus CFC vs CFC: OR = 1.61, 95% CI [1.17-2.21], I2 = 0%, P = .004; trastuzumab plus OT vs OT: OR = 4.29, 95% CI [2.33-7.90], I2 = 0%, P < .0001; and trastuzumab plus CC vs CC: OR = 2.99, 95% CI [1.99-4.48], I2 = 0%, P < .0001). However, there were no significant differences in the adverse events. CONCLUSIONS: The results of this study revealed that the efficacy of trastuzumab combined with chemotherapy was superior to that of chemotherapy alone for the treatment of HER2-PAGC. The 2 modalities showed similar safety profiles.

A mechanistic motor-clutch model that explains cell shape dynamics to cyclic stretch.

Many cells in the body experience cyclic mechanical loading, which can impact cellular processes and morphology. In vitro studies often report that cells reorient in response to cyclic stretch of their substrate. To explore cellular mechanisms involved in this reorientation, a computational model was developed by adapting previous computational models of the actin-myosin-integrin motor-clutch system developed by others. The computational model predicts that under most conditions, actin bundles align perpendicular to the direction of applied cyclic stretch, but under specific conditions, such as low substrate stiffness, actin bundles align parallel to the direction of stretch. The model also predicts that stretch frequency impacts the rate of reorientation and that proper myosin function is critical in the reorientation response. These computational predictions are consistent with reports from the literature and new experimental results presented here. The model suggests that the impact of different stretching conditions (stretch type, amplitude, frequency, substrate stiffness, etc.) on the direction of cell alignment can largely be understood by considering their impact on cell-substrate detachment events, specifically whether detachments preferentially occur during stretching or relaxing of the substrate.

Modified FOLFIRINOX for unresectable locally advanced or metastatic gallbladder cancer, a comparison with GEMOX regimen.

BACKGROUND: The first-line chemotherapy regimen for advanced gallbladder cancer (GBC) is gemcitabine plus platinum (GP), despite its efficacy is limited. The current investigation is a retrospective study to compare the safety and efficacy between the modified FOLFIRINOX (mFOLFIRINOX) and gemcitabine plus oxaliplatin (GEMOX) as the first-line chemotherapy for unresectable locally advanced or metastatic GBC. METHODS: The data of patients with unresectable locally advanced or metastatic GBC, who were treated with mFOLFIRINOX or GEMOX as the first-line therapy between April 2014 and April 2018 at Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, were retrieved. This retrospective study evaluated the clinical characteristics, survival outcomes and adverse events. RESULTS: A total of 44 patients (n=25 in mFOLFIRINOX, n=19 in GEMOX) were included. There were no significant differences between groups in baseline characteristics. The median progression free survival (mPFS) was 5.0 months in the mFOLFIRINOX group and 2.5 months in the GEMOX group [P=0.021; hazard ratio (HR), 0.499; 95% CI, 0.266 to 0.937]. The median overall survival (mOS) was 9.5 months in the mFOLFIRINOX group and 7.0 months in the GEMOX group (P=0.019; HR, 0.471; 95% CI, 0.239 to 0.929). Disease control rate (DCR) was 76.0% in the mFOLFIRINOX group and 47.4% in the GEMOX group (P=0.051). The rate of grade 3-4 adverse events was 48% in the mFOLFIRINOX group and 36.8% in the GEMOX group (P=0.459). The incidence of grade 3-4 neutropenia and diarrhea were more common in the mFOLFIRINOX group, while the incidence of grade 3-4 thrombocytopenia and peripheral neuropathy were more common in the GEMOX group. CONCLUSIONS: mFOLFIRINOX might improve the poor prognosis of unresectable locally advanced or metastatic GBC, and the results need to be further verified by prospective clinical studies.

Development and Validation of a Prognostic Nomogram Based on the Systemic Immune-Inflammation Index for Resectable Gallbladder Cancer to Predict Survival and Chemotherapy Benefit.

OBJECTIVES: To investigate the prognostic significance of the systemic immune-inflammation index (SII) in patients after radical cholecystectomy for gallbladder cancer (GBC) using overall survival (OS) as the primary outcome measure. METHODS: Based on data from a multi-institutional registry of patients with GBC, significant prognostic factors after radical cholecystectomy were identified by multivariate Cox proportional hazards model. A novel staging system was established, visualized as a nomogram. The response to adjuvant chemotherapy was compared between patients in different subgroups according to the novel staging system. RESULTS: Of the 1072 GBC patients enrolled, 691 was randomly selected in the discovery cohort and 381 in the validation cohort. SII>510 was found to be an independent predictor of OS (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.42-2.54). Carbohydrate antigen 199(CA19-9), tumor differentiation, T stage, N stage, margin status and SII were involved in the nomogram. The nomogram showed a superior prediction compared with models without SII (1-, 3-, 5-year integrated discrimination improvement (IDI):2.4%, 4.1%, 5.4%, P<0.001), and compared to TNM staging system (1-, 3-, 5-year integrated discrimination improvement (IDI):5.9%, 10.4%, 12.2%, P<0.001). The C-index of the nomogram in predicting OS was 0.735 (95% CI 0.683-0.766). The novel staging system based on the nomogram showed good discriminative ability for patients with T2 or T3 staging and with negative lymph nodes after R0 resection. Adjuvant chemotherapy offered significant survival benefits to these patients with poor prognosis. CONCLUSIONS: SII was an independent predictor of OS in patients after radical cholecystectomy for GBC. The new staging system identified subgroups of patients with T2 or T3 GBC with negative lymph nodes who benefited from adjuvant chemotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier (NCT04140552).

Genome-wide identification of target genes for transcription factor BR-C in the silkworm, Bombyx mori.

Transcription factor Broad Complex (BR-C) is an ecdysone primary response gene in insects and participates in the regulation of insect growth and development. In this study, we performed a genome-wide identification of BR-C target genes in silkworm (Bombyx mori) using chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq). As a result, a total of 1006 BR-C ChIP peaks were identified, and 15% of peaks were located in the promoter regions of 133 protein-coding genes. Functional annotation revealed that these ChIP peak-associated genes, as potential BR-C targets, were enriched in pathways related to biosynthetic process, metabolic process, and development. Transcriptome analysis and quantitative real-time polymerase chain reaction (PCR) examination revealed that developmental changes in expression patterns of a portion of potential BR-C targets, including HR96 and GC-α1, were similar to those of BR-C. ChIP-PCR examination confirmed that BR-C could directly bind to the promoters of potential targets. Further, dual luciferase assays demonstrated that HR96 promoter activity was significantly upregulated following BR-C overexpression, and this upregulation was abolished when the binding motif in the promoter was truncated. This study will be helpful for deciphering the regulatory roles of BR-C during insect growth and development.

A 3D porous microsphere with multistage structure and component based on bacterial cellulose and collagen for bone tissue engineering.

Collagen (COL) and bacterial cellulose (BC) were chemically recombined by Malaprade and Schiff-base reactions. A three-dimensional (3D) porous microsphere of COL/BC/Bone morphogenetic protein 2 (BMP-2) with multistage structure and components were prepared by the template method combined with reverse-phase suspension regeneration. The microspheres were full of pores and had a rough surface. The particle size ranged from 8 to 12 microns, the specific surface area (SBET) was 123.4 m2/g, the pore volume (VPore) was 0.59 cm3/g, and the average pore diameter (DBJH) was 198.5 nm. The adsorption isotherm of the microspheres on the N2 molecule belongs to that of mesoporous materials. The microspheres showed good biocompatibility, and the 3D porous microspheres with multiple structures and components effectively promoted the adhesion, proliferation, and osteogenic differentiation of mice MC3T3-E1 cells. The study can provide a theoretical basis for the application of COL/BC porous microspheres in the field of bone tissue engineering.

Multiscale phenomena and patterns in biological systems: special issue in honour of Hans Othmer.

This special issue on "Multiscale phenomena and patterns in biological systems" is an homage to the seminal contributions of Hans Othmer. He has remained at the forefront of multiscale modelling and pattern formation in biology for over half a century, developing models for molecular signalling networks, the mechanics of cellular movements, the interactions between multiple cells and their contributions to tissue patterning and dynamics. The contributions in this special issue follow Hans' legacy in using advanced mathematics to understand complex biological processes.

Spatial pattern formation in reaction-diffusion models: a computational approach.

Reaction-diffusion equations have been widely used to describe biological pattern formation. Nonuniform steady states of reaction-diffusion models correspond to stationary spatial patterns supported by these models. Frequently these steady states are not unique and correspond to various spatial patterns observed in biology. Traditionally, time-marching methods or steady state solvers based on Newton's method were used to compute such solutions. However, the solutions that these methods converge to highly depend on the initial conditions or guesses. In this paper, we present a systematic method to compute multiple nonuniform steady states for reaction-diffusion models and determine their dependence on model parameters. The method is based on homotopy continuation techniques and involves mesh refinement, which significantly reduces computational cost. The method generates one-parameter steady state bifurcation diagrams that may contain multiple unconnected components, as well as two-parameter solution maps that divide the parameter space into different regions according to the number of steady states. We applied the method to two classic reaction-diffusion models and compared our results with available theoretical analysis in the literature. The first is the Schnakenberg model which has been used to describe biological pattern formation due to diffusion-driven instability. The second is the Gray-Scott model which was proposed in the 1980s to describe autocatalytic glycolysis reactions. In each case, the method uncovers many, if not all, nonuniform steady states and their stabilities.

Drugs adsorption and release behavior of collagen/bacterial cellulose porous microspheres.

A porous microsphere with good biocompatibility was fabricated based on collagen (COL) and bacterial cellulose (BC). The adsorption and release behaviors of the COL/BC porous microspheres were studied using BSA as the model protein, and employing quasi-primary, quasi-secondary, and Kannan-Sundaram intragranular diffusion models, zero-order, first-order, Higuchi and Korsmeyer-Peppas models. The results showed that the COL/BC porous microspheres are beneficial to the proliferation of MC3T3 E1-cells. The linear Langmuir equation can accurately describe the adsorption equilibrium relationship of BSA to the COL/BC microspheres. The pseudo-second-order model can more accurately explain and predict the membrane diffusion kinetics of BSA than both pseudo-primary-order and Kannan-Sundaram intragranular diffusion models. The adsorption rate was affected by both membrane and intragranular diffusions. The drug release behavior indicated that the microsphere-loaded BSA was primarily adsorbed at the inner wall of the pore, and exhibited the characteristics of a scaffold-based matrix meanwhile. The drug release kinetics can be accurately described by the first-order release model. The present study elucidated the mechanism of drug adsorption and release of COL/BC porous microspheres and provided a theoretical basis for its application in controlled release technology.

A stochastic model that explains axonal organelle pileups induced by a reduction of molecular motors.

Nerve cells are critically dependent on the transport of intracellular cargoes, which are moved by motor proteins along microtubule tracks. Impairments in this movement are thought to explain the focal accumulations of axonal cargoes and axonal swellings observed in many neurodegenerative diseases. In some cases, these diseases are caused by mutations that impair motor protein function, and genetic depletion of functional molecular motors has been shown to lead to cargo accumulations in axons. The evolution of these accumulations has been compared to the formation of traffic jams on a highway, but this idea remains largely untested. In this paper, we investigated the underlying mechanism of local axonal cargo accumulation induced by a global reduction of functional molecular motors in axons. We hypothesized that (i) a reduction in motor number leads to a reduction in the number of active motors on each cargo which in turn leads to less persistent movement, more frequent stops and thus shorter runs; (ii) as cargoes stop more frequently, they impede the passage of other cargoes, leading to local 'traffic jams'; and (iii) collisions between moving and stopping cargoes can push stopping cargoes further away from their microtubule tracks, preventing them from reattaching and leading to the evolution of local cargo accumulations. We used a lattice-based stochastic model to test whether this mechanism can lead to the cargo accumulation patterns observed in experiments. Simulation results of the model support the hypothesis and identify key questions that must be tested experimentally.

The role of intracellular signaling in the stripe formation in engineered Escherichia coli populations.

Recent experiments showed that engineered Escherichia coli colonies grow and self-organize into periodic stripes with high and low cell densities in semi-solid agar. The stripes develop sequentially behind a radially propagating colony front, similar to the formation of many other periodic patterns in nature. These bacteria were created by genetically coupling the intracellular chemotaxis pathway of wild-type cells with a quorum sensing module through the protein CheZ. In this paper, we develop multiscale models to investigate how this intracellular pathway affects stripe formation. We first develop a detailed hybrid model that treats each cell as an individual particle and incorporates intracellular signaling via an internal ODE system. To overcome the computational cost of the hybrid model caused by the large number of cells involved, we next derive a mean-field PDE model from the hybrid model using asymptotic analysis. We show that this analysis is justified by the tight agreement between the PDE model and the hybrid model in 1D simulations. Numerical simulations of the PDE model in 2D with radial symmetry agree with experimental data semi-quantitatively. Finally, we use the PDE model to make a number of testable predictions on how the stripe patterns depend on cell-level parameters, including cell speed, cell doubling time and the turnover rate of intracellular CheZ.

Starving honey bee (Apis mellifera) larvae signal pheromonally to worker bees.

Cooperative brood care is diagnostic of animal societies. This is particularly true for the advanced social insects, and the honey bee is the best understood of the insect societies. A brood pheromone signaling the presence of larvae in a bee colony has been characterised and well studied, but here we explored whether honey bee larvae actively signal their food needs pheromonally to workers. We show that starving honey bee larvae signal to workers via increased production of the volatile pheromone E-ß-ocimene. Analysis of volatile pheromones produced by food-deprived and fed larvae with gas chromatography-mass spectrometry showed that starving larvae produced more E-ß-ocimene. Behavioural analyses showed that adding E-ß-ocimene to empty cells increased the number of worker visits to those cells, and similarly adding E-ß-ocimene to larvae increased worker visitation rate to the larvae. RNA-seq and qRT-PCR analysis identified 3 genes in the E-ß-ocimene biosynthetic pathway that were upregulated in larvae following 30 minutes of starvation, and these genes also upregulated in 2-day old larvae compared to 4-day old larvae (2-day old larvae produce the most E-ß-ocimene). This identifies a pheromonal mechanism by which brood can beg for food from workers to influence the allocation of resources within the colony.

Moment-flux models for bacterial chemotaxis in large signal gradients.

Chemotaxis is a fundamental process in the life of many prokaryotic and eukaryotic cells. Chemotaxis of bacterial populations has been modeled by both individual-based stochastic models that take into account the biochemistry of intracellular signaling, and continuum PDE models that track the evolution of the cell density in space and time. Continuum models have been derived from individual-based models that describe intracellular signaling by a system of ODEs. The derivations rely on quasi-steady state approximations of the internal ODE system. While this assumption is valid if cell movement is subject to slowly changing signals, it is often violated if cells are exposed to rapidly changing signals. In the latter case current continuum models break down and do not match the underlying individual-based model quantitatively. In this paper, we derive new PDE models for bacterial chemotaxis in large signal gradients that involve not only the cell density and flux, but also moments of the intracellular signals as a measure of the deviation of cell's internal state from its steady state. The derivation is based on a new moment closure method without calling the quasi-steady state assumption of intracellular signaling. Numerical simulations suggest that the resulting model matches the population dynamics quantitatively for a much larger range of signals.