An eco-friendly porous hydrogel adsorbent based on dextran/phosphate/amino for efficient removal of Be(II) from aqueous solution.

A novel environmentally-friendly porous hydrogel adsorbent (GHPN) is firstly designed and prepared using dextran, phosphate, and calcium hydroxide for the adsorption of Be(II). GHPN shows good adsorption selectivity for Be(II) (Kd = 1.53 × 104 mL/g). According the adsorption kinetics and thermodynamics, the theoretical adsorption capacity of GHPN to Be(II) is 43.75 mg/g (35 °C, pH = 6.5), indicating a spontaneous exothermic reaction. After being reused for 5 cycles, the adsorption and desorption efficiencies of Be(II) with GHPN are obtained to be more than 80 %, showing acceptable recycling performance. Both of the characterizations and theoretical calculations indicate that the phosphate group, hydroxyl group, and amino group own the affinity to form stable complexes with Be(II). Benefiting from the introduction of phosphate and amino, the adsorption effect of the hydrogel adsorbent on Be(II) can be greatly improved, and surface precipitation, complexation, and ligand exchange are the dominant mechanisms of beryllium adsorption. The results suggest that GHPN has great potential to be utilized as an eco-friendly and useful adsorbent of Be(II) from aqueous solution.

Quasi-10-day waves in temperature and polar mesospheric clouds: Results of AIM/SOFIE and Aura/MLS observations.

Planetary waves, including quasi-2, -5, -10, -16-day waves, play significant roles in stratospheric dynamics. However, the existing knowledge on quasi-10-day waves (Q10DWs) at high latitudes is limited. This paper investigated the interannual and seasonal variations of Q10DWs with zonal wave numbers varying from the -3 (westward propagation) to 3 (eastward propagation) modes from 2008 to 2022, using temperature data measured by the Microwave Limb Sounder instrument (316-0.001 hPa, corresponding to an altitude of approximately 8-97 km) and temperature/ice water content data measured by the Solar Occultation for Ice Experiment (SOFIE) instrument (10-100 km at latitudes >55°). The findings revealed that the amplitude of Q10DWs in winter was higher than that in other seasons. The amplitude of Q10DWs was observed to substantially decrease with an increase in wavenumber. In addition, the amplitude of stationary Q10DWs in the northern polar region exceeded that in the southern polar region. Moreover, we used observational data from the SOFIE instrument, which simultaneously measures temperature and ice water content (IWC) in the mesosphere, to examine the variations of Q10DWs with respect to the temperature and IWC. Our findings suggest that in the northern polar region, the maximum value of Q10DWs in IWC was occasionally observed earlier than the lowest value of Q10DWs in temperatures.

Accuracy of flapless surgery using an autonomous robotic system in full-arch immediate implant restoration: A case series.

OBJECTIVES: This observational study aimed to evaluate the accuracy of robotic computer-assisted implant surgery (r-CAIS) for full-arch immediate restoration and to analyse possible factors contributing to deviations. METHODS: Three edentulous patients (five arches) underwent r-CAIS. Osteotomies were performed using an autonomous robot under the surgeon's supervision, and implant placement was performed in a freehand or robotic manner. Prefabricated provisional prostheses were delivered immediately after surgery. Postoperative cone beam computed tomography scans were performed to assess the deviations between the planned and placed implants. Statistics were compared with deviations of s-CAIS outlined in a meta-analysis. RESULTS: A sum of 28 implants were used. The mean global coronal and apical deviations measured 0.91 ± 0.43 mm and 1.01 ± 0.45 mm, respectively, and the mean angular deviation measured 1.21 ± 1.24 º. The r-CAIS showed significantly better precision than the s-CAIS in full-arch cases (P < 0.001). The implants inserted using the robotic arm exhibited fewer deviations than those placed in the freehand manner. Eighty percent of prefabricated provisional prostheses were successfully delivered. CONCLUSIONS: Within the limitations of the present study, our data suggest that autonomous r-CAIS is a feasible approach for simultaneous immediate restoration in edentulous patients, showing better accuracy than s-CAIS. Further large-scale studies are necessary to verify the advantages and disadvantages of this novel technique and to explore possible factors that influence its accuracy. CLINICAL SIGNIFICANCE: Autonomous r-CAIS can provide clinically acceptable implant placement accuracy in edentulous patients, significantly surpassing s-CAIS. This level of accuracy may represent a viable therapeutic approach for simultaneous immediate full-arch restoration.

Insights into optimal surgical fixation for posterior malleolar fractures.

Aims: The optimal management of posterior malleolar ankle fractures, a prevalent type of ankle trauma, is essential for improved prognosis. However, there remains a debate over the most effective surgical approach, particularly between screw and plate fixation methods. This study aims to investigate the differences in outcomes associated with these fixation techniques. Methods: We conducted a comprehensive review of clinical trials comparing anteroposterior (A-P) screws, posteroanterior (P-A) screws, and plate fixation. Two investigators validated the data sourced from multiple databases (MEDLINE, EMBASE, and Web of Science). Following PRISMA guidelines, we carried out a network meta-analysis (NMA) using visual analogue scale and American Orthopaedic Foot and Ankle Score (AOFAS) as primary outcomes. Secondary outcomes included range of motion limitations, radiological outcomes, and complication rates. Results: The NMA encompassed 13 studies, consisting of four randomized trials and eight retrospective ones. According to the surface under the cumulative ranking curve-based ranking, the A-P screw was ranked highest for improvements in AOFAS and exhibited lowest in infection and peroneal nerve injury incidence. The P-A screws, on the other hand, excelled in terms of VAS score improvements. Conversely, posterior buttress plate fixation showed the least incidence of osteoarthritis grade progression, postoperative articular step-off ≥ 2 mm, nonunions, and loss of ankle dorsiflexion ≥ 5°, though it underperformed in most other clinical outcomes. Conclusion: The NMA suggests that open plating is more likely to provide better radiological outcomes, while screw fixation may have a greater potential for superior functional and pain results. Nevertheless, clinicians should still consider the fragment size and fracture pattern, weighing the advantages of rigid biomechanical fixation against the possibility of soft-tissue damage, to optimize treatment results.

Effects of endoplasmic reticulum stress on chondrocyte apoptosis via the PI3K/AKT signaling pathway.

Chondrocytes undergo endoplasmic reticulum stress (ERS)-induced apoptosis under abnormal stimulation. However, the underlying molecular mechanism remains unclear. We investigated the regulatory effect of the PI3K/AKT signaling pathway on ERS and its effect on chondrocyte apoptosis. In addition, we established a unilateral anterior crossbite (UAC) model in rats to induce temporomandibular joint osteoarthritis (TMJOA). Chondrocytes were isolated from the temporomandibular joints and treated with lipopolysaccharide (LPS) in vitro. Protein expression of ERS and apoptosis markers (GRP78 and CASP12) was analyzed by immunohistochemistry and western blotting. The expression of GRP78, CASP12, p-PI3K, and p-AKT significantly increased in the UAC group. LY294002, a PI3K/AKT signaling pathway inhibitor, reduced the protein expression of GRP78, ATF4, CHOP, and CASP12, whereas 740 Y-P, an activation agent, elevated the expression of proteins GRP78, ATF4, CHOP, and CASP12. In the present study, UAC and LPS stimulation induced apoptosis of chondrocytes in the ERS pathway. Inhibition of the PI3K/AKT signaling pathway reduced ERS-induced chondrocyte apoptosis.

Porous durian shell biochar modified by KMnO4 (Mn-DSB) as a highly selective adsorbent for Be(II).

The mining of uranium-beryllium ores has resulted in substantial beryllium (Be) contamination. In this study, agricultural waste durian shells were utilized as raw materials to prepare biochar, which was further modified to enhance its adsorption capacity (Mn-DSB). The results effectively demonstrated Mn loading onto the DSB surface. Batch experiments were conducted to identify the optimal adsorption conditions of Mn-DSB for beryllium. At a temperature of 35 °C and pH 6, beryllium's maximum adsorption capacity (Qe) was 42.08 mg·g-1. The materials' internal structure was analyzed before and after adsorption via multiple techniques. Mn-DSB manifested potent selectivity towards beryllium in multicomponent mixed solutions, binary systems, and uranium-beryllium wastewater, as the beryllium removal rate exceeded 90%. The study investigated the recyclability of Mn-DSB and found that after five reuse cycles, the adsorption and desorption efficiencies were 90% and 85%, respectively. The strong ligand complexation (N-H, CO32-, -OH) and ion exchange mechanisms (with Mn7+ ions) of Mn-DSB explained its high adsorption capacity. Therefore, this study demonstrates the potential of Mn-DSB for treating uranium-beryllium tailing wastewater.

PRMT-7/PRMT7 activates HLH-30/TFEB to guard plasma membrane integrity compromised by bacterial pore-forming toxins.

Bacterial pore-forming toxins (PFTs) that disrupt host plasma membrane integrity (PMI) significantly contribute to the virulence of various pathogens. However, how host cells protect PMI in response to PFT perforation in vivo remains obscure. Previously, we demonstrated that the HLH-30/TFEB-dependent intrinsic cellular defense (INCED) is elicited by PFT to maintain PMI in Caenorhabditis elegans intestinal epithelium. Yet, the molecular mechanism for the full activation of HLH-30/TFEB by PFT remains elusive. Here, we reveal that PRMT-7 (protein arginine methyltransferase-7) is indispensable to the nuclear transactivation of HLH-30 elicited by PFTs. We demonstrate that PRMT-7 participates in the methylation of HLH-30 on its RAG complex binding domain to facilitate its nuclear localization and activation. Moreover, we showed that PRMT7 is evolutionarily conserved to regulate TFEB cellular localization and repair plasma damage caused by PFTs in human intestinal cells. Together, our observations not only unveil a novel PRMT-7/PRMT7-dependent post-translational regulation of HLH-30/TFEB but also shed insight on the evolutionarily conserved mechanism of the INCED against PFT in metazoans.

Comparing the accuracies of freehand, static computer-assisted and robot-assisted dental implant placements: an in vitro study.

OBJECTIVE: To compare the accuracies among three oral implant surgical techniques: freehand (FH), static computer-assisted implant surgery (sCAIS), and robotic computer-assisted implant surgery (rCAIS). METHODS: The polyurethane and bovine femur implant models were fabricated, and 126 and 96 implant sites were designed on them. The implant sites were divided into three groups: FH, sCAIS, and rCAIS, according to the implantation method. The deviation between the actual implant position and the planned position was analyzed and compared by cone beam computed tomography. RESULTS: In the polyurethane model test, the entry deviation, entry-level deviation, apical deviation, apical level deviation, and angle deviation in sCAIS and rCAIS groups were significantly reduced compared with those in the FH group (P<0.05). No significant differences were observed in all kinds of deviations between the sCAIS and rCAIS groups (P>0.05). In the bovine femur model test, the entry deviation, entry-level deviation, apical deviation, apical level deviation, and angle deviation in both sCAIS and rCAIS groups were significantly reduced compared with those in the FH group (P<0.05). No significant differences were observed in all kinds of deviations between the sCAIS and rCAIS groups (P>0.05). CONCLUSION: This in vitro study shows that the rCAIS technique is superior to the freehand, but has the same accuracy as the sCAIS.

Haemolysin Ahh1 secreted from Aeromonas dhakensis activates the NLRP3 inflammasome in macrophages and mediates severe soft tissue infection.

Severe soft tissue infections caused by Aeromonas dhakensis, such as necrotizing fasciitis or cellulitis, are prevalent in southern Taiwan and around the world. However, the mechanism by which A. dhakensis causes tissue damage remains unclear. Here, we found that the haemolysin Ahh1, which is the major virulence factor of A. dhakensis, causes cellular damage and activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome signalling pathway. Deletion of ahh1 significantly downregulated caspase-1, the proinflammatory cytokine interleukin 1ß (IL-1ß) and gasdermin D (GSDMD) and further decreased the damage caused by A. dhakensis in THP-1 cells. In addition, we found that knockdown of the NLRP3 inflammasome confers resistance to A. dhakensis infection in both THP-1 NLRP3-/- cells and C57BL/6 NLRP3-/- mice. In addition, we demonstrated that severe soft-tissue infections treated with antibiotics combined with a neutralizing antibody targeting IL-1ß significantly increased the survival rate and alleviated the degree of tissue damage in model mice compared control mice. These findings show that antibiotics combined with therapies targeting IL-1ß are potential strategies to treat severe tissue infections caused by toxin-producing bacteria.

MESPEUS: a database of metal coordination groups in proteins.

MESPEUS is a freely accessible database which uses carefully selected metal coordination groups found in metalloprotein structures taken from the Protein Data Bank. The database contains geometrical information of metal sites within proteins, including 40 metal types. In order to completely determine the metal coordination, the symmetry-related units of a given protein structure are taken into account and are generated using the appropriate space group symmetry operations. This permits a more complete description of the metal coordination geometry by including all coordinating atoms. The user-friendly web interface allows users to directly search for a metal site of interest using several useful options, including searching for metal elements, metal-donor distances, coordination number, donor residue group, and structural resolution. These searches can be carried out singly or in combination. The details of a metal site and the metal site(s) in the whole structure can be graphically displayed using the interactive web interface. MESPEUS is automatically updated monthly by synchronizing with the PDB database. An investigation for the Mg-ATP interaction is given to demonstrate how MESPEUS can be used to extract information about metal sites by selecting structure and coordination features. MESPEUS is available at http://mespeus.nchu.edu.tw/.

Determining the Optimal Treatment for Idiopathic Clubfoot: A Network Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Clubfoot, or congenital talipes equinovarus deformity, is a common anomaly affecting the foot in infants. However, clinical equipoise remains between different interventions, especially those based on the Ponseti method. The aim of this study was to examine the clinical outcomes of the various interventions for treating idiopathic clubfoot. METHODS: Searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Scopus, and CINAHL were conducted. Randomized controlled trials comparing different interventions, including the Ponseti method, accelerated Ponseti method, Ponseti method with botulinum toxin type A (Botox) injection, Ponseti method with early tibialis anterior tendon transfer (TATT), Kite method, and surgical treatment, were included. Network meta-analyses (NMAs) were conducted according to the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) reporting guidelines. The primary outcomes were the change in total Pirani score and maximal ankle dorsiflexion. Secondary outcomes were the number of casts, time in casts, and rates of tenotomy, total complications, relapse, adverse events, and additional required major surgery. RESULTS: Eleven randomized controlled trials involving 740 feet were included. According to the SUCRA (surface under the cumulative ranking curve)-based relative ranking, the Ponseti method was associated with the best outcomes in terms of Pirani score changes, maximal ankle dorsiflexion, number of casts, adverse events, and total complications, whereas the accelerated Ponseti method was associated with the best outcomes in terms of time in casts and tenotomy rate. Early TATT ranked best in terms of relapse rate. The Ponseti method with Botox injection was associated with the best outcomes in terms of the need for additional major surgery. CONCLUSIONS: The NMAs suggest that the Ponseti method is the optimal treatment overall, despite potential drawbacks such as longer time in casts and higher rates of tenotomy, relapse, and the need for additional surgery compared with other modified approaches. Therefore, clinicians should consider how treatments can be tailored individually. LEVEL OF EVIDENCE: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Accuracy of an optical robotic computer-aided implant system and the trueness of virtual techniques for measuring robot accuracy evaluated with a coordinate measuring machine in vitro.

STATEMENT OF PROBLEM: A unified standard for measuring robot implantation errors has not yet been established. A coordinate measuring machine (CMM) measures the coordinates of an object with high accuracy. However, evaluations of the accuracy of a robotic computer-assisted implant system (R-CAIS) using CMM are lacking. PURPOSE: The purpose of this in vitro study was to evaluate the accuracy of an optics-based R-CAIS using a CMM and to assess the accuracy of cone beam computed tomography (CBCT), a laboratory scanner (LS), and an intraoral scanner (IOS) in measuring the accuracy of the R-CAIS. MATERIAL AND METHODS: Two 60×50×40-mm cubic models were prepared for the experiment. One master model and several replica models were used for the first part. Employing a robotic system software, virtual planning was performed on the digital imaging and communications in medicine (DICOM) image of the master model, and spatial mapping was performed by using an optical tracking marker (OT-marker) to ensure that virtual planning of the master model could be executed when replica casts were drilled and placed the implants. The actual placements of the implants in the replica casts were measured by using CMM. The errors between the actual and virtual-planned positions were calculated. In the second part, virtual planning was performed on the experimental model, and an optics-based R-CAIS was used to drill holes and place the implants. The actual positions of the implants were measured by using CMM, CBCT, LS, and IOS. The errors between the actual and virtual-planned positions were calculated, and the error results among groups were compared by 1-way analysis of variance or a nonparametric test. The Dunnett test was used for post hoc comparison (α=.05). RESULTS: In the first part, the entry, apical, and angle deviations were 0.33 ±0.10 mm, 0.41 ±0.11 mm, and 0.33 ±0.13 degrees, respectively. In the second part, as compared with CMM, no statistically significant differences were observed in the LS group (P>.05), whereas significant differences were observed in entry-depth, entry, apical-depth, apical, and angle deviations in the IOS group, as well as in entry-depth and apical-depth deviations in the CBCT group (all P<.05). CONCLUSIONS: The optical-based R-CAIS exhibited high accuracy. The application of CBCT for clinical implantation may be close to that of the true deviation.

A Low-Cost, Sensitive Reporter System Using Membrane-Tethered Horseradish Peroxidase for Efficient Gene Expression Analysis.

Reporter gene assays are essential for high-throughput analysis, such as drug screening or determining downstream signaling activation/inhibition. However, use of this technology has been hampered by the high cost of the substrate (e.g., d-Luciferin (d-Luc)) in the most common firefly luciferase (FLuc) reporter gene assay. Although alternate luciferase is available worldwide, its substrate has remained expensive, and a more affordable option is still in demand. Here, we present a membrane-tethered horseradish peroxidase (mHRP), a new reporter system composed of a cell membrane expressing HRP that can preserve its enzymatic function on the cell surface, facilitates contact with HRP substrates (e.g., ABTS and TMB), and avoids the cell lysis process and the use of the high-priced luciferase substrate. An evaluation of the light signal sensitivity of mHRP compared to FLuc showed that both had comparable signal sensitivity. We also identified an extended substrate half-life of more than 5-fold that of d-Luc. Of note, this strategy provided a more stable detection signal, and the cell lysis process is not mandatory. Furthermore, with this strategy, we decreased the total amount of time taken for analysis and increased the time of detection limit of the reporter assay. Pricing analysis showed a one-third to one twenty-eighth price drop per single test of reporter assay. Given the convenience and stability of the mHRP reporter system, we believe that our strategy is suitable for use as an alternative to the luciferase reporter assay.

Can a propensity score matching method be applied to assessing efficacy from single-arm proof-of-concept trials in oncology?

As a result of the escalating number of new cancer treatments being developed and competition among pharmaceutical companies, decisions regarding how to proceed with phase III trials are frequently based on findings from either single-arm phase I expansion cohorts or phase II studies that compare the efficacy of the study drug to a standard-of-care benchmark derived from historical data. However, even when eligibility criteria are matched, differences in the distribution of baseline patient features may influence the outcome of single-arm trials in real-world scenarios. Therefore, novel methods are needed to enhance the accuracy of efficacy prediction from current cohorts relative to historical data. In this study, we demonstrated the feasibility of using the propensity score matching (PSM) method to improve decision making by matching relevant baseline features between current and historical cohorts. According to our findings, utilizing the PSM method may provide a less biased means of comparing outcomes between current and historical cohorts relative to a naïve approach, which relies solely on differences in average outcomes between the cohorts.

The Antimicrobial Effects of Colistin Encapsulated in Chelating Complex Micelles for the Treatment of Multi-Drug-Resistant Gram-Negative Bacteria: A Pharmacokinetic Study.

Background: Infections caused by multi-drug-resistant Gram-negative bacteria (MDR-GNB) are an emerging problem globally. Colistin is the last-sort antibiotic for MDR-GNB, but its toxicity limits its clinical use. We aimed to test the efficacy of colistin-loaded micelles (CCM-CL) against drug-resistant Pseudomonas aeruginosa and compare their safety with that of free colistin in vitro and in vivo. Materials and methods: We incorporated colistin into chelating complex micelles (CCMs), thus producing colistin-loaded micelles (CCM-CL), and conducted both safety and efficacy surveys to elucidate their potential uses. Results: In a murine model, the safe dose of CCM-CL was 62.5%, which is much better than that achieved after the intravenous bolus injection of 'free' colistin. With a slow drug infusion, the safe dose of CCM-CL reached 16 mg/kg, which is double the free colistin, 8 mg/kg. The area under the curve (AUC) levels for CCM-CL were 4.09- and 4.95-fold higher than those for free colistin in terms of AUC0-t and AUC0-inf, respectively. The elimination half-lives of CCM-CL and free colistin groups were 12.46 and 102.23 min, respectively. In the neutropenic mice model with carbapenem-resistant Pseudomonas aeruginosa pneumonia, the 14-day survival rate of the mice treated with CCM-CL was 80%, which was significantly higher than the 30% in the free colistin group (p < 0.05). Conclusions: Our results showed that CCM-CL, an encapsulated form of colistin, is safe and effective, and thus may become a drug of choice against MDR-GNB.

Effect of mechanical-chemical modification on adsorption of beryllium by calcite.

The treatment of beryllium wastewater has become a major problem in industry. In this paper, CaCO3 is creatively proposed to treat beryllium-containing wastewater. Calcite was modified by an omnidirectional planetary ball mill by a mechanical-chemical method. The results show that the maximum adsorption capacity of CaCO3 for beryllium is up to 45 mg/g. The optimum treatment conditions were pH = 7 and the amount of adsorbent was 1 g/L, and the best removal rate was 99%. The concentration of beryllium in the CaCO3-treated solution is less than 5 µg/L, which meets the international emission standard. The results show that the surface co-precipitation reaction between CaCO3 and Be (II) mainly occurs. Two different precipitates are generated on the used-CaCO3 surface; one is the tightly connected Be (OH)2 precipitation, and the other is the loose Be2(OH)2CO3 precipitation. When the pH of the solution exceeds 5.5, Be2+ in the solution is first precipitated by Be (OH)2. After CaCO3 is added, CO32- will further react with Be3(OH)33+ to form Be2(OH)2CO3 precipitation. CaCO3 can be considered as an adsorbent with great potential to remove beryllium from industrial wastewater.

Is implant choice associated with fixation strength for displaced radial neck fracture: a network meta-analysis of biomechanical studies.

The multitude of fixation options for radial neck fractures, such as pins, screws, biodegradable pins and screws, locking plates, and blade plates, has led to a lack of consensus on the optimal implant choice and associated biomechanical properties. This study aims to evaluate the biomechanical strength of various fixation constructs in axial, sagittal, and torsional loading directions. We included biomechanical studies comparing different interventions, such as cross/parallel screws, nonlocking plates with or without augmented screws, fixed angle devices (T or anatomic locking plates or blade plates), and cross pins. A systematic search of MEDLINE (Ovid), Embase, Scopus, and CINAHL EBSCO databases was conducted on September 26th, 2022. Data extraction was carried out by one author and verified by another. A network meta-analysis (NMA) was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Primary outcomes encompassed axial, bending, and torsional stiffness, while the secondary outcome was bending load to failure. Effect sizes were calculated for continuous outcomes, and relative treatment ranking was measured using the surface under the cumulative ranking curve (SUCRA). Our analysis encompassed eight studies, incorporating 172 specimens. The findings indicated that fixed angle constructs, specifically the anatomic locking plate, demonstrated superior axial stiffness (mean difference [MD]: 23.59 N/mm; 95% CI 8.12-39.06) in comparison to the cross screw. Additionally, the blade plate construct excelled in bending stiffness (MD: 32.37 N/mm; 95% CI - 47.37 to 112.11) relative to the cross screw construct, while the cross-screw construct proved to be the most robust in terms of bending load failure. The parallel screw construct performed optimally in torsional stiffness (MD: 139.39 Nm/degree; 95% CI 0.79-277.98) when compared to the cross screw construct. Lastly, the nonlocking plate, locking T plate, and cross-pin constructs were found to be inferior in most respects to alternative interventions. The NMA indicated that fixed angle devices (blade plate and anatomic locking plate) and screw fixations may exhibit enhanced biomechanical strength in axial and bending directions, whereas cross screws demonstrated reduced torsional stability in comparison to parallel screws. It is imperative for clinicians to consider the application of these findings in constraining forces across various directions during early range of motion exercises, taking into account the distinct biomechanical properties of the respective implants.

Merged Lateral Row Modification of the Suture Bridge Technique for Simultaneous Supraspinatus and Subscapularis Repair.

Concomitate supraspinatus and subscapularis tear is not rare, and the suture bridge technique is one of the most effective methods for rotator cuff repair. However, some limitations exist in the use of such a technique for simultaneous supraspinatus and subscapularis repair. We introduce the technique of a merged lateral row for suture bridge rotator cuff repair, in which the lateral suture of the supraspinatus and subscapularis is placed in the greater tuberosity. We believe that this technique can reduce both the duration and cost of surgery and decrease soft-tissue damage. It can also allow the "comma tissue," to be simultaneously repaired.

A lesion-selective albumin-CTLA4Ig as a safe and effective treatment for collagen-induced arthritis.

BACKGROUND: CTLA4Ig is a dimeric fusion protein of the extracellular domain of cytotoxic T-lymphocyte protein 4 (CTLA4) and an Fc (Ig) fragment of human IgG1 that is approved for treating rheumatoid arthritis. However, CTLA4Ig may induce adverse effects. Developing a lesion-selective variant of CTLA4Ig may improve safety while maintaining the efficacy of the treatment. METHODS: We linked albumin to the N-terminus of CTLA4Ig (termed Alb-CTLA4Ig) via a substrate sequence of matrix metalloproteinase (MMP). The binding activities and the biological activities of Alb-CTLA4Ig before and after MMP digestion were analyzed by a cell-based ELISA and an in vitro Jurkat T cell activation assay. The efficacy and safety of Alb-CTLA4Ig in treating joint inflammation were tested in mouse collagen-induced arthritis. RESULTS: Alb-CTLA4Ig is stable and inactive under physiological conditions but can be fully activated by MMPs. The binding activity of nondigested Alb-CTLA4Ig was at least 10,000-fold weaker than that of MMP-digested Alb-CTLA4Ig. Nondigested Alb-CTLA4Ig was unable to inhibit Jurkat T cell activation, whereas MMP-digested Alb-CTLA4Ig was as potent as conventional CTLA4Ig in inhibiting the T cells. Alb-CTLA4Ig was converted to CTLA4Ig in the inflamed joints to treat mouse collagen-induced arthritis, showing similar efficacy to that of conventional CTLA4Ig. In contrast to conventional CTLA4Ig, Alb-CTLA4Ig did not inhibit the antimicrobial responses in the spleens of the treated mice. CONCLUSIONS: Our study indicates that Alb-CTLA4Ig can be activated by MMPs to suppress tissue inflammation in situ. Thus, Alb-CTLA4Ig is a safe and effective treatment for collagen-induced arthritis in mice.

A flexible liposomal polymer complex as a platform of specific and regulable immune regulation for individual cancer immunotherapy.

BACKGROUND: The applicability and therapeutic efficacy of specific personalized immunotherapy for cancer patients is limited by the genetic diversity of the host or the tumor. Side-effects such as immune-related adverse events (IRAEs) derived from the administration of immunotherapy have also been observed. Therefore, regulatory immunotherapy is required for cancer patients and should be developed. METHODS: The cationic lipo-PEG-PEI complex (LPPC) can stably and irreplaceably adsorb various proteins on its surface without covalent linkage, and the bound proteins maintain their original functions. In this study, LPPC was developed as an immunoregulatory platform for personalized immunotherapy for tumors to address the barriers related to the heterogenetic characteristics of MHC molecules or tumor associated antigens (TAAs) in the patient population. Here, the immune-suppressive and highly metastatic melanoma, B16F10 cells were used to examine the effects of this platform. Adsorption of anti-CD3 antibodies, HLA-A2/peptide, or dendritic cells' membrane proteins (MP) could flexibly provide pan-T-cell responses, specific Th1 responses, or specific Th1 and Th2 responses, depending on the host needs. Furthermore, with regulatory antibodies, the immuno-LPPC complex properly mediated immune responses by adsorbing positive or negative antibodies, such as anti-CD28 or anti-CTLA4 antibodies. RESULTS: The results clearly showed that treatment with LPPC/MP/CD28 complexes activated specific Th1 and Th2 responses, including cytokine release, CTL and prevented T-cell apoptosis. Moreover, LPPC/MP/CD28 complexes could eliminate metastatic B16F10 melanoma cells in the lung more efficiently than LPPC/MP. Interestingly, the melanoma resistance of mice treated with LPPC/MP/CD28 complexes would be reversed to susceptible after administration with LPPC/MP/CTLA4 complexes. NGS data revealed that LPPC/MP/CD28 complexes could enhance the gene expression of cytokine and chemokine pathways to strengthen immune activation than LPPC/MP, and that LPPC/MP/CTLA4 could abolish the LPPC/MP complex-mediated gene expression back to un-treatment. CONCLUSIONS: Overall, we proved a convenient and flexible immunotherapy platform for developing personalized cancer therapy.