Self-enhanced PTX@HSA-HA loaded functionalized injectable hydrogel for effective local chemo-photothermal therapy in breast cancer.

Breast cancer is a malignant tumor that poses a significant threat to women's health and single therapy fails to play a good oncological therapeutic effect. Synergistic treatment with multiple strategies may make up for the deficiencies and has gained widespread attention. In this study, sulfhydryl-modified hyaluronic acid (HA-SH) was covalently crosslinked with polydopamine (PDA) via a Michael addition reaction to develop an injectable hydrogel, in which PDA can be used not only as a matrix but also as a photothermal agent. After HSA and paclitaxel were spontaneously organized into nanoparticles via hydrophobic interaction, hyaluronic acid with low molecular weight was covalently linked to HSA, thus conferring effectively delivery. This photothermal injectable hydrogel incorporates PTX@HSA-HA nanoparticles, thereby initiating a thermochemotherapeutic response to target malignancy. Our results demonstrated that this injectable hydrogel possesses consistent drug delivery capability in a murine breast cancer model, collaborating with photothermal therapy to effectively suppress tumor growth, represented by low expression of Ki-67 and increasing apoptosis. Photothermal therapy (PTT) can effectively stimulate immune response by increasing IL-6 and TNF-α. Notably, the treatment did not elicit any indications of toxicity. This injectable hydrogel holds significant promise as a multifaceted therapeutic agent that integrates photothermal and chemotherapeutic modalities.

Effect of graphene oxide in an injectable hydrogel on the osteogenic differentiation of mesenchymal stem cells.

Graphene oxide (GO) is widely used in bone tissue engineering due to its good biocompatibility and proliferation, and is often used in combination with other hydrogels, which not only reduces the cytotoxicity of GO but also improves the mechanical properties of the hydrogels. We developed injectable carboxymethyl chitosan (CMC)/hydroxyethyl cellulose (HEC)/ß-tricalcium phosphate (ß-TCP)/GO hydrogel via hydrogen bonding cross-linked between (CMC) and (HEC), also, calcium cross-linked by ß-TCP was also involved to further improvement of mechanical properties of the hydrogel, and incorporate different concentration of GO in these hydrogel systems. The characterization of the novel hydrogel was tested by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). The swelling ratio and mechanical properties were investigated, the results showed that the addition of GO was able to reduce the swelling rate of hydrogels and improve their mechanical properties, with the best effect in the case of 1 mg/mL content. In vivo experimental studies showed that the hydrogel significantly promoted the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), with the best effect at a concentration of 2 mg/mL. The results of the cellular experiments were similar. Therefore, the novel environment-friendly and non-toxic injectable CMC/HEC/ß-TCP/GO hydrogel system may have potential applications in bone tissue engineering.

Association of antipsychotic formulations with sudden cardiac death in patients with schizophrenia: A nationwide population-based case-control study.

The aim of this study was to clarify the association between various antipsychotic formulations-oral-daily antipsychotics (OAPs), long-acting injectable antipsychotics (LAIs), and their combination-and the risk of sudden cardiac death (SCD). We conducted a nationwide population-based case-control study using data from 2011 to 2020 from the National Health Insurance Research Database and multiple-cause-of-death data from Taiwan. The study included patients with a new diagnosis of schizophrenia who were followed for SCD occurrence until 2020. Cases and controls were frequency-matched at a 1:4 ratio by age, sex, and year of new schizophrenia diagnosis. Compared with the use of OAP monotherapy, the use of LAI and OAP combination (OR = 1.91) and LAI monotherapy (OR = 1.45) were associated with an increased risk of SCD. Additionally, cardiovascular comorbidities (adjusted OR = 11.15) were identified as a significant risk factor for SCD. This study revealed the following hierarchy of SCD risk associated with antipsychotic formulations (listed from lowest to highest risk): nonuse of antipsychotics, OAP monotherapy, LAI monotherapy, and their combination. These findings underscore the importance of assessing cardiovascular disease history before LAIs are prescribed to patients with schizophrenia and indicate that physicians should avoid prescribing combined antipsychotics when using LAIs.

Rapid preparation of injectable dual-network hydrogels for biomedical applications using UV-triggered sulfhydryl click reactions.

The use of hydrogels to mimic natural cartilage implantation can effectively solve the current problems of insufficient cartilage donors and low rate of injury healing. In particular, injectable hydrogels are less invasive in clinical applications and better able to fill uneven injury surfaces. Here, we prepared NorCS and CS-SH by modifying chitosan with 5-norbornene-2-carboxylic acid and N-Acetyl-L-cysteine, respectively. Dual-network hydrogels were prepared by using UV-triggered thiol-ene click reaction between NorCS and CS-SH and the metal coordination between SA and Ca2+. The prepared hydrogels can be cross-linked quickly and exhibit excellent degradability, self-healing and injectable properties. At the same time, the hydrogel also showed good cytocompatibility and could significantly restore the motor function of mice. This study provides an effective strategy for preparing injectable hydrogels capable of rapid cross-linking.

Inpatient initiation of long-acting injectable buprenorphine at a community hospital: A retrospective case series.

OBJECTIVES: Determine if long-acting injectable buprenorphine (LAIB) can be successfully and safely administered in the hospital with minimal sublingual buprenorphine lead-in and potentially improve follow-up engagement in care. METHODS: We performed a retrospective case series of 46 patients who received LAIB while hospitalized at a safety-net community hospital. We abstracted demographic information, details about substance use disorder treatment history, in-hospital buprenorphine initiation methods and follow-up data from inpatient and outpatient electronic medical records. RESULTS: In total, 46 hospitalized patients received LAIB during the study period. The majority of our patients were older Black adults with Medicaid who self-reported intranasal heroin use. A low-dose buprenorphine initiation protocol was used most commonly, either in sublingual or intravenous form, with only two cases of precipitated withdrawal occurring during the buprenorphine initiation process and no cases of precipitated withdrawal after the administration of LAIB. 87% (40) of the patients received LAIB after receiving either sublingual or IV buprenorphine for fewer than the recommended seven days. Of the 46 hospitalized patients who received LAIB, 23 (50%) attended a follow-up addiction medicine appointment within 30 days of discharge. CONCLUSIONS: Hospital administration of LAIB could play an important role in retention in care after hospital discharge.

A photothermal responsive system accelerating nitric oxide release to enhance bone repair by promoting osteogenesis and angiogenesis.

Managing bone defects remains a formidable clinical hurdle, primarily attributed to the inadequate orchestration of vascular reconstruction and osteogenic differentiation in both spatial and temporal dimensions. This challenge persists due to the constrained availability of autogenous grafts and the limited regenerative capacity of allogeneic or synthetic bone substitutes, thus necessitating continual exploration and innovation in the realm of functional and bioactive bone graft materials. While synthetic scaffolds have emerged as promising carriers for bone grafts, their efficacy is curtailed by deficiencies in vascularization and osteoinductive potential. Nitric oxide (NO) plays a key role in revascularization and bone tissue regeneration, yet studies related to the use of NO for the treatment of bone defects remain scarce. Herein, we present a pioneering approach leveraging a photothermal-responsive system to augment NO release. This system comprises macromolecular mPEG-P nanoparticles encapsulating indocyanine green (ICG) (NO-NPs@ICG) and a mPEG-PA-PP injectable thermosensitive hydrogel carrier. By harnessing the synergistic photothermal effects of near-infrared radiation and ICG, the system achieves sustained NO release, thereby activating the soluble guanylate cyclase (SGC)-cyclic guanosine monophosphate (cGMP) signaling pathway both in vitro and in vivo. This orchestrated cascade culminates in the facilitation of angiogenesis and osteogenesis, thus expediting the reparative processes in bone defects. In a nutshell, the NO release-responsive system elucidated in this study presents a pioneering avenue for refining the bone tissue microenvironment and fostering enhanced bone regeneration.

Manufacture, characterization, and elucidation of drug release mechanisms of etonogestrel implants based on ethylene vinyl acetate.

In this work, etonogestrel implants were manufactured using coextrusion. The purpose of the study was to correlate changes in microstructure and transport properties that occurred in etonogestrel implants to drug release mechanisms. The implants consisted of an EVA 28 (28% vinyl acetate) core containing dispersed and dissolved etonogestrel, and an EVA 15 (15% vinyl acetate) skin. The drug release was determined to be via diffusion at a controlled rate and governed by implant dimensions. In-vitro release revealed evidence of supersaturation in the implant core and skin, likely from the intense mechanical energy input during the twin-screw manufacturing process. Subsequently during storage under ambient conditions, supersaturation resulted in recrystallization of drug crystals, preferentially in the implant core. Etonogestrel solubility and diffusivity in EVA were determined by permeation experiments and used for release modeling. Drug release from the EVA skin layer deviated from the predicted values due to 1) formation of a drug depletion zone in the core and 2) presence of a stagnant media layer adjacent to the skin. Drug release from implant ends was significantly faster than predicted. Air-filled pores were observed in the implant core using microCT which likely contributed to the faster release from implant ends.

Alginate-based injectable probiotic/squid ink composite hydrogels for accelerated wound healing of MRSA infected abscess through photothermally synergized probiotic therapy.

Methicillin-resistant Staphylococcus aureus (MRSA) infections pose great challenges to skin wound care due to the severe drug resistance developed in the clinic. There is an urgent need to exploit next-generation bactericidal therapeutics that are both antibiotic-free and multifunctional for enhanced wound healing. Herein, we designed a Ca2+-crosslinked alginate hydrogel (EcNSIN@Alg) containing two naturally derived bioactive components, probiotics Escherichia coli Nissle1917 (EcN) and Squid ink nanoparticles (SIN), to treat MRSA-infected wounds. The injectable composite hydrogel displayed excellent biocompatibility, photothermal antibacterial activity, and reactive oxygen species (ROS) scavenging property. Importantly, the probiotic EcN can enhance the photothermal SIN to promote immune regulatory activities, shifting pro-inflammatory macrophages (M1) to anti-inflammatory macrophages (M2). In an MRSA-infected abscess model, EcNSIN@Alg can reduce the expression level of wound inflammatory factors and ROS, increase the number of anti-inflammatory macrophages, accelerate collagen deposition and promote wound healing. This work offers a new perspective on developing safe, antibiotic-free, multifunctional bactericides using fully bioderived materials, with potential applications in clinical practice.

Therapeutic failure reported with HIV long-acting injectables: An analysis of the FDA Adverse Event Reporting System from 2021 to 2024.

OBJECTIVES: We examined adverse event (AE) reports relating to cabotegravir/rilpivirine (CAB/RPV) in the US FDA Adverse Event Reporting System (FAERS), focusing on therapeutic failure (TF) and non-therapeutic failure (NTF) outcomes. METHODS: FAERS is a database of AE and medication error reports from post-marketing surveillance. The study was granted exempt approval by the Binghamton University Institutional Review Board. We queried reports for CAB/RPV in the FAERS system from 1 January 2021 to 31 March 2024. TFs were defined as involving any of the following terms: viral load increased, virological failure, pathogen resistance, blood HIV RNA increased, treatment failure, drug ineffective, viral mutation identified, viraemia, and therapy non-responder. The top 20 most common AEs were also identified. Means, standard deviations, and percentages were used to characterize the sample. RESULTS: The study cohort consisted of 2605 reports. The reported sex of the study cohort was 50% male (n = 1295), 19% female (n = 505), and 31% unspecified (n = 805), with a mean ± standard deviation (SD) age of 46.9 ± 12.4 years (n = 378). The top three most reported AEs were TFs, product dose omissions, and injection site pain, with 377 (14.5%), 354 (13.6%), and 331 (12.7%) cases, respectively. The mean ± SD weight of people with a report of TF versus NTF was 101.8 ± 33.4 kg and 87.7 ± 26.7 kg, respectively (p = 0.0175). CONCLUSION: Our findings suggest that healthcare professionals should have a heightened awareness of potential challenges with CAB/RPV administration, including TFs and dose omissions in real-world settings.

Thermo-sensitive Poloxamer based antibacterial anti-inflammatory and photothermal conductive multifunctional hydrogel as injectable, in situ curable and adjustable intraocular lens.

Cataract patients look forwards to fewer postoperative complications and higher vision quality after surgery. However, the current intraocular lens (IOL) implanted after cataract surgery neither can adjust focal length in response to ciliary muscle contraction as natural lens nor have the ability to prevent postoperative complications. Herein, a thermosensitve Poloxamer based hybrid hydrogel with antibacterial anti-inflammatory and photothermal functional elements doping was designed and used as injectable, in situ curable, and adjustable IOL (FHTAB IOL). The FHTAB IOL was composed of thermosensitve triblock-polymer F127DA and a small amount of HAMA, combined with BP NS, TA, and Ag NPs. FHTAB IOL can be injected into the empty lens capsule after cataract surgery via an injectable thermos-gel under NIR illumination and then be rapidly cured to form a full-size IOL under short-time blue light irradiation. The designed injectable FHTAB IOL possesses high transparency and transmittance, with a refractive index similar to the natural lens and adjustable properties. It was stabilized as a refractive medium without any leakage in the eye. In addition, the TA and Ag NPs loaded in the FHTAB IOL displayed significant antibacterial and anti-inflammatory effects in vitro and vivo. This study presents a potentially effective new strategy for the development of multifunctional adjustable IOLs.

Medication burden reduction and early clinical benefit through aripiprazole once monthly in schizophrenia patients with polypharmacy.

Antipsychotic polypharmacy is commonly used in clinical settings, with a growing trend in using long-acting injections to mitigate many side effects of polypharmacy. A previous study demonstrated that long-acting aripiprazole once-monthly (AOM) injection increased treatment adherence, restored functionality, and improved symptoms. However, there is insufficient evidence to demonstrate the therapeutic effects of AOM in polypharmacy practice. This observational study aimed to investigate the real-world clinical benefits and effectiveness of AOM by assessing changes in drug dosage, the number of drugs, clinical functioning, psychotic symptoms, and the duration of drug efficacy. Study participants were recruited from eight study sites, with the baseline visit marking the initiation of drug treatment. Clinical and demographic data were collected from medical records at screening, baseline, and months 1, 3, 6, 9, and 12. Over 12 months, we analyzed changes in drug dosage, the number of drugs, and scores of the Positive and Negative Syndrome Scale-6 (PANSS-6), Global Assessment of Functioning (GAF), and Clinical Global Impression-Severity (CGIS). Data from 139 participants were analyzed. Total 12-month antipsychotic doses calculated in chlorpromazine equivalents (CPE) were reduced by 32.6%. A comparison of total monthly antipsychotic doses in CPE between the first and last months showed a 24.6% reduction in the dose. Additionally, the quantity of benzodiazepine tablets/capsules, total benzodiazepine doses calculated in lorazepam equivalents, and quantity of tablets/capsules of mood stabilizers, anticholinergics, and beta blockers were significantly reduced. GAF scores increased by 14.1% over 12 months, and PANSS-6 total scores reduced by 17.3% over 12 months, with significant differences observed from month 1 and baseline, respectively. The scores steadily improved until month 9 compared to those of the previous months, continuing to improve through month 12. The CGI-S score reduced by 14.3% over 12 months, showing a significant decrease from month 1 and a steady improvement until month 6, maintaining this improvement until month 12. In conclusion, this study demonstrated the early effectiveness of AOM in treating Korean patients with schizophrenia on polypharmacy. AOM improved function and clinical symptoms in patients with schizophrenia from treatment onset and caused a decrease in the quantity and dosage of drugs taken by the patients.

Quality by design steered approach for co-encapsulation of timolol maleate and dorzolamide hydrochloride in injectable liposomes.

Glaucoma is caused by high intraocular pressure, which can causes blindness. Combinations of timolol and dorzolamide are used for its treatment with a requirement of multiple dosing with dosing being twice or four times a day. Conventional eye drops have poor pre-corneal retention and is thus less available for action. This study utilizes principles of Quality by Design for formulation of injectable liposomes coloaded with timolol maleate and dorzolamide HCl, which overcomes limitations of conventional eye drops. For implementation of Quality by Design principles a systematic approach involving defining Quality Target Product Profile, identification of Critical Quality Attributes, mapping Critical Quality Attributes to Critical Process Parameters and Critical Material Attributes, Failure Mode and Effect Analysis based risk assessment, Taguchi screening, and 32 full factorial Design of Experiments design were utilized. A robust model for formulation of coloaded liposomes was successfully developed. Design of Experiments approach allowed to obtain optimized batch having particle size of 116.1 nm, encapsulation efficiency of dorzolamide HCl of 72.12 % and encapsulation efficiency of timolol maleate of 71.94 %. In-vitro drug release showed a sustained release for 4 days. The prepared formulation was in the desired osmolarity range. Biosafety was proved using histopathological characterization. In-vivo studies for assessing the Intra Ocular Pressure reduction showed that there was no significant difference in Intra Ocular Pressure reduction between prepared liposomes and marketed formulation but were superior than marketed formulation because of less fluctuations in Intra Ocular Pressure. Prepared coloaded injectable liposomes lays the foundation for further research in the area and can be translated from to bench side for commercial clinical use.

Willingness to Use Long-acting Injectable Pre-exposure Prophylaxis Among Key Populations at a Large Hiv Prevention Clinic in Kampala, Uganda: a Cross-sectional Study.

Background: Long-acting injectable (LAI)-PrEP provides better protection against HIV compared to oral PrEP, which requires taking a daily pill. Our study aimed to assess knowledge about oral and LAI-PrEP and identify factors associated with willingness to use LAI-PrEP among key populations (KP) in Uganda. Methods: We conducted a cross-sectional study at the Most at Risk Populations Initiative (MARPI) clinic between November and December 2021. Participants were recruited through convenience sampling and interviewed using a structured questionnaire by trained interviewers. Participants were categorised into three groups based on their oral PrEP use: those who had not yet initiated PrEP, those who had discontinued oral PrEP, and those currently on oral PrEP. Modified Poisson regression analysis was performed to determine factors associated with the participant's willingness to use LAI-PrEP. Data was analysed using STATA 14 software. Results: Of the 234 participants, 135 (56.7%) were female, 82.5% knew about LAI-PrEP, and 67.5% were willing to use it. The mean age was 28.7 years (standard deviation [SD] 5.8). Willingness to use LAI-PrEP was less likely among divorced, widowed, or separated individuals than those in relationships (adjusted prevalence ratio [aPR] 0.65, 95% CI: 0.43-0.98). Relative to current oral PrEP users, willingness to use LAI-PrEP was similar among those who discontinued oral PrEP (aPR 1.39, 95% CI: 0.92-2.11) and those who had not yet initiated PrEP but were at risk for HIV (aPR 1.26, 95% CI: 0.83-1.89). Conclusions: In this cross-sectional analysis of diverse members of key populations in Uganda, previous or non-use of oral PrEP was not associated with willingness to use LAI-PrEP relative to current users. Future studies should investigate effective methods for promoting the uptake of long-acting PrEP formulations among populations at high risk of HIV acquisition.

Evaluating the impact of COVID-19 on medication adherence and health care utilization among individuals with psychotic disorders who are prescribed long-acting injectables (LAIs) or clozapine: A population-based study in Manitoba, Canada.

BACKGROUND: Ongoing psychiatric follow-up and medication adherence improve outcomes for patients with psychotic disorders. Due to COVID-19, outpatient care may have been disrupted, impacting healthcare utilization. METHODS: A retrospective population-wide study was conducted for adults in Manitoba, Canada. Medication adherence and healthcare utilization were examined from 2019 to 2021. The presence of a diagnosed psychotic disorder was identified in the five years before the index date in each year. The LAI and clozapine cohorts consisted of those who received at least two prescriptions in each year 180 days before the March 20th index date. The change in adherence was measured using the average Medication Possession Ratio. Healthcare utilization rates were compared using Generalized Estimating Equation models. RESULTS: There were no significant differences between LAI and clozapine discontinuation rates before and during the pandemic. In the LAI cohort, general practitioner visits decreased significantly (-3.5 %, p = 0.039) across four quarters of 2021 versus 2019. All-cause hospitalizations decreased by 16.8 % in 2020 versus 2019 (p = 0.0055), while psychiatric hospitalizations decreased by 18.7 % across four quarters in 2020 (p = 0.0052) and 13.7 % in 2021 (p = 0.0425), versus 2019 in the LAI cohort. There was a significant transition to virtual care during the first wave of COVID-19 (71 % in clozapine, 51 % in LAI cohorts). Trends in total outpatient visits and non-psychiatric hospitalizations remained stable. CONCLUSION: COVID-19 had no substantial impact on LAI and clozapine discontinuation rates for patients previously adherent. Outpatient care remained stable, with a significant proportion of visits being done virtually at the outset of the pandemic.

Barriers to Oral PrEP: A Qualitative Study of Female Sex Workers, PrEP Prescribers, Policymakers, and Community Advocates in Morocco.

In 2017, Morocco became the first Arab country to incorporate pre-exposure prophylaxis (PrEP) in its HIV-prevention program. Yet no research has been published on PrEP from Morocco. Although female sex workers are one of the target populations of PrEP in Morocco, their enrollment in PrEP is lower than men who have sex with men. In this study, we conducted 38 semi-structured interviews with female sex workers, physicians who prescribe PrEP, policymakers, and community advocates to identify problems associated with access to and use of PrEP. We also investigated preferences for daily oral, vaginal ring, and long-acting injectable PrEP. A reflexive thematic analysis revealed seven themes: PrEP stigma; stigmatization and criminalization of sex work; one size doesn't fit all; knowledge and misconceptions about PrEP; economic burden; inconvenience of PrEP pills; and preferred PrEP modalities. This paper discusses the implications of the findings for increasing access and use of PrEP in Morocco.

Factors that Influence Uptake of Oral PrEP among Female Sex Workers One of the most recent scientific advancements in the history of the HIV pandemic was the introduction of pre-exposure prophylaxis (PrEP). However, the uptake of PrEP in the Arab world is low. In this paper we interviewed female sex workers, physicians who prescribe PrEP, policymakers, and community advocates to identify problems associated with access to and use of PrEP. Several barriers were identified including stigma attached to PrEP, misconceptions about PrEP, and financial burden. Although most female sex workers in our study were interested in using PrEP, the delivery methods of PrEP should be tailored to fit the lifestyle and personal circumstances of potential users.

An injectable oleogel-based bupivacaine formulation for prolonged non-opioid post-operative analgesia.

Opioid-based medications remain the mainstay of post-operative pain management, even though they are associated with a plethora of adverse effects including addiction, nausea, constipation, cognitive impairment, respiratory depression, and accidental death due to overdose. Local anesthetics are effective at controlling the intense pain after surgery but their short duration of effect limits their clinical utility in post-operative pain management. In this manuscript, an optimized injectable oleogel-based formulation of bupivacaine for multi-day post-operative pain management was characterized on the benchtop and assessed in two clinically-relevant porcine post-operative pain models. Benchtop characterization verified the optimized oleogel-based bupivacaine formulation design, demonstrating a homogenous stable oleogel with sufficient injectability due to shear-thinning properties, high drug loading capacity and first-order drug release kinetics over 5 days. In vivo assessment in two pig post-operative pain models demonstrated that the oleogel-based bupivacaine formulation can provide statistically significant multi-day analgesia in two routes of administration: local instillation directly into a surgical site and ultrasound-guided peripheral nerve block injection. Pharmacokinetic assessment of ALX005 found that Cmax values were not statistically different from the bupivacaine HCl control, with no clinical signs of local anesthetic systemic toxicity observed, when administering up to 2.7 and 8.1 times the control dose of bupivacaine HCl. This study demonstrates the pre-clinical safety and efficacy of an injectable oleogel-based bupivacaine formulation and explores its utility as a single-administration long-acting local anesthetic product for post-operative pain management that can be used in both local and regional anesthetic applications.

An injectable biomimetic hydrogel adapting brain tissue mechanical strength for postoperative treatment of glioblastoma without anti-tumor drugs participation.

Adapting the mechanical strength between the implant materials and the brain tissue is crucial for the postoperative treatment of glioblastoma. However, no related study has been reported. Herein, we report an injectable lipoic acid­iron (LA-Fe) hydrogel (LFH) that can adapt to the mechanical strength of various brain tissues, including human brain tissue, by coordinating Fe3+ into a hybrid hydrogel of LA and its sodium salt (LANa). When LFH, which matches the mechanical properties of mouse brain tissue (337 ± 8.06 Pa), was injected into the brain resection cavity, the water content of the brain tissue was maintained at a normal level (77%). Similarly, LFH did not induce the activation or hypertrophy of glial astrocytes, effectively preventing brain edema and scar hyperplasia. Notably, LFH spontaneously degrades in the interstitial fluid, releasing LA and Fe3+ into tumor cells. The redox couples LA/DHLA (dihydrolipoic acid, reduction form of LA in cells) and Fe3+/Fe2+ would regenerate each other to continuously provide ROS to induce ferroptosis and activate immunogenic cell death. As loaded the anti-PDL1, anti-PDL1@LFH further enhanced the efficacy of tumor-immunotherapy and promoted tumor ferroptosis. The injectable hydrogel that adapted the mechanical strength of tissues shed a new light for the tumor postoperative treatment.

Long-acting antipsychotic treatments: focus on women with schizophrenia.

Effective management of schizophrenia (SZ) requires long-term treatment with antipsychotics (APs) to prevent clinical relapse, attain remission and improve patients' personal and social functioning, and quality of life. Although APs remain the cornerstone treatment for patients with SZ, despite their potential benefits, long-acting injectable APs (LAI-APs) remain underused, most notably in women with SZ. The efficacy and tolerability of APs differ significantly between men and women, and some of these differences are more noticeable depending on the patient's age and the stage of the disorder. Although sex differences may influence treatment outcomes in SZ, their pertinence has been insufficiently addressed, especially regarding the use of LAI-APs. Some biological and social experiences, such as pregnancy, lactation, contraception and menopause, are specific to women, but these remain under-researched issues. Implications of this disorder in parenting are also of special pertinence regarding women; therefore, taking sex differences into account when treating SZ patients is now recommended, and improving personalized approaches has been proposed as a priority in the management of psychosis. In this narrative, critical review, we address some aspects specific to sex and their implications for the clinical management of women with SZ, with a special focus on the potential role of LAI-AP treatments.

• Schizophrenia is a chronic mental illness, and patients often need to take antipsychotic medications in the long-run in order to stay well, avoid re-occurrence of symptoms and improve their everyday functioning and quality of life. • Antipsychotics are available in both pill and injection form. The latter is known as long-acting injectable antipsychotics (LAI-APs) and can be administered from weekly to twice a year. • Despite their effectiveness and practicality due to less frequent administration, LAI-APs remain largely underused, especially in women with schizophrenia. • The efficacy and tolerability of antipsychotics can be very different between men and women, and some of these differences may be more pronounced depending on the patient's age and the phase of the illness. • Notably, physical and social aspects such as pregnancy, lactation, contraception, parenting and menopause and their effects on the treatment with antipsychotics and particularly LAI-APs in women with schizophrenia are under-studied. • Nevertheless, we have now become more aware of the importance of these sex differences, and it is recommended to take them routinely into consideration when treating patients with schizophrenia in clinical practice. • In this article, we discuss how factors specific to sex can influence the treatment of women with schizophrenia and focus on the potential role of LAI-AP medications.

Injectable citrate-based polyurethane-urea as a tug-of-war-inspired bioactive self-expansive and planar-fixing screw augmented bone-tendon healing.

Inspired by tug-of-war, a game-changing bone-tendon fixation paradigm was developed. Specifically, injectable citrate-based bioactive self-expansive and planar-fixing screw (iCSP-Scr) consisting of reactive isocyanate (NCO) terminalized citrate-based polyurethane, proanthocyanidin modified hydroxyapatite (HAp) and water (with/without porogen) was developed and administrated in the bone-tendon gap. Instead of the "point to point" tendon fixation by traditional interface screws, along with the moisture-induced crosslinking and expansion of iCSP-Scr within the confined space of the irregularly shaped bone-tendon gap, the tendon graft was evenly squeezed into the bone tunnel in a "surface to surface" manner to realize strong and stable bone-tendon fixation via physical expansion, mechanical interlocking and chemical bonding (between -NCO and the -NH2, -SH groups on bone matrix). The optimized iCSP-Scr exhibited rapid crosslinking, moderate expansion rate, high porosity after crosslinking, as well as tunable elasticity and toughness. The iCSP-Scr possessed favorable biodegradability, biocompatibility, and osteoinductivity derived from citrate, PC and HAp, it was able to promote osteogenesis and new bone growth inward of bone tunnel thus further enhanced the bone/iCSP-Scr mechanical interlock, ultimately leading to stronger tendon fixation (pull-out force 106.15 ± 23.15 N) comparing to titanium screws (93.76 ± 17.89 N) after 14 weeks' ACL reconstruction in a rabbit model. The iCSP-Scr not only can be used as a self-expansive screw facilitating bone-tendon healing, but also can be expanded into other osteogenic application scenarios.