Generation of rat forebrain tissues in mice.

Interspecies blastocyst complementation (IBC) provides a unique platform to study development and holds the potential to overcome worldwide organ shortages. Despite recent successes, brain tissue has not been achieved through IBC. Here, we developed an optimized IBC strategy based on C-CRISPR, which facilitated rapid screening of candidate genes and identified that Hesx1 deficiency supported the generation of rat forebrain tissue in mice via IBC. Xenogeneic rat forebrain tissues in adult mice were structurally and functionally intact. Cross-species comparative analyses revealed that rat forebrain tissues developed at the same pace as the mouse host but maintained rat-like transcriptome profiles. The chimeric rate of rat cells gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late pre-natal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRISPR-based IBC strategy holds great potential to broaden the study and application of interspecies organogenesis.

Independent Evolution of Sex Chromosomes and Male Pregnancy-Related Genes in Two Seahorse Species.

Unlike birds and mammals, many teleosts have homomorphic sex chromosomes, and changes in the chromosome carrying the sex-determining locus, termed "turnovers", are common. Recent turnovers allow studies of several interesting questions. One question is whether the new sex-determining regions evolve to become completely non-recombining, and if so, how and why. Another is whether (as predicted) evolutionary changes that benefit one sex accumulate in the newly sex-linked region. To study these questions, we analyzed the genome sequences of two seahorse species of the Syngnathidae, a fish group in which many species evolved a unique structure, the male brood pouch. We find that both seahorse species have XY sex chromosome systems, but their sex chromosome pairs are not homologs, implying that at least one turnover event has occurred. The Y-linked regions occupy 63.9% and 95.1% of the entire sex chromosome of the two species and do not exhibit extensive sequence divergence with their X-linked homologs. We find evidence for occasional recombination between the extant sex chromosomes that may account for their homomorphism. We argue that these Y-linked regions did not evolve by recombination suppression after the turnover, but by the ancestral nature of the low crossover rates in these chromosome regions. With such an ancestral crossover landscape, a turnover can instantly create an extensive Y-linked region. Finally, we test for adaptive evolution of male pouch-related genes after they became Y-linked in the seahorse.

Epidermodysplasia Verruciformis and Vδ2 γδ T-cell Expansion in STK4 Deficiency.

The clinical penetrance of infectious diseases varies considerably among patients with inborn errors of immunity (IEI), even for identical genetic defects. This variability is influenced by pathogen exposure, healthcare access and host-environment interactions. We describe here a patient in his thirties who presented with epidermodysplasia verruciformis (EV) due to infection with a weakly virulent beta-papillomavirus (HPV38) and CD4+ T-cell lymphopenia. The patient was born to consanguineous parents living in the United States. Exome sequencing identified a previously unknown biallelic STK4 stop-gain mutation (p.Trp425X). The patient had no relevant history of infectious disease during childhood other than mild wart-like lesion on the skin, but he developed diffuse large B-cell lymphoma (DLBCL) and EBV viremia with a low viral load in his thirties. Despite his low CD4+ T-cell count, the patient had normal counts of CD3+ cells, predominantly double-negative T cells (67.4%), which turned out to be Vδ2+ γδ T cells. γδ T-cell expansion has frequently been observed in the 33 reported cases with STK4 deficiency. The Vδ2 γδ T cells of this STK4-deficient patient are mostly CD45RA-CD27+CCR7+ central memory γδT cells, and their ability to proliferate in response to T-cell activation was impaired, as was that of CD4+ T cells. In conclusion, γδ T-cell expansion may act as a compensatory mechanism to combat viral infection, providing immune protection in immunocompromised individuals.

Clinical and genetic characterization of a Chinese family with pontocerebellar hypoplasia type 7.

We report compound heterozygous variants in TOE1 in siblings of Chinese origin who presented with dyskinesia and intellectual disabilities. Our report provides further information regarding the etiology and pathogenesis of pontocerebellar hypoplasia type 7 syndrome (PCH7). Clinical manifestations were obtained, and genomic DNA was collected from family members. Whole-exome and Sanger sequencing were performed to identify associated genetic variants. Bioinformatics analysis was conducted to identify and characterize the pathogenicity of the heterozygous variants. Following long-term rehabilitation, both siblings showed minimal improvement, and their condition tended to progress. Whole-exome sequencing revealed two unreported heterozygous variants, NM_025077: c.C553T (p.R185W) and NM_025077: c.G562T (p.V188L), in the TOE1 gene mapped to 1p34.1. Sanger sequencing confirmed that the two variants in the proband and her brother were inherited from their parents. The NM_025077: c.C553T (p.R185W) variant was inherited from the father, and the NM_025077: c.G562T (p.V188L) variant was inherited from the mother. Although the two variants in the TOE1 gene have not been reported previously, they were associated with PCH7 based on integrated analysis. Thus, our report contributes to our knowledge regarding the etiology and phenotype of PCH 7.

Irreversible Electroporation-Induced Inflammation Facilitates Neutrophil-Mediated Drug Delivery to Enhance Pancreatic Cancer Therapy.

Pancreatic cancer is a deadly disease with a five-year overall survival rate of around 11%. Chemotherapy is a cornerstone in the treatment of this malignancy, but the intratumoral delivery of chemotherapy drugs is impaired by the highly fibrotic tumor-associated stroma. Irreversible electroporation (IRE) is an ablative technique for treating locally advanced pancreatic cancer. During a typical IRE procedure, high-intensity electric pulses are released to kill tumor cells through the irreversible disruption of the cytoplasm membranes. IRE also induces rapid tumor infiltration by neutrophils and offers an opportunity for neutrophil-mediated drug delivery. We herein showed that the IRE-induced neutrophil trafficking was facilitated by the upregulation of neutrophil chemotaxis and migration as well as the release of several chemoattractants. Doxorubicin-loaded bovine serum albumin nanoparticles were prepared and loaded into neutrophils at a ratio of 9.9 ± 1.2 to 11.7 ± 2.0 pg of doxorubicin per cell. The resultant formulation (NP@NEs) efficiently accumulated in the IRE-treated KPC-A377 murine pancreatic tumors with an uptake value of 10.7 ± 1.5 (percent of injected dose per gram of tissue, abbreviated as %ID/g) at 48 h after intravenous injection. In both Panc02 and KPC-A377 murine pancreatic tumor models, the combination of IRE + NP@NEs inhibited tumor growth more effectively than either monotherapy. The tumors treated with the combination also exhibited the lowest frequency of Ki67+ proliferating cells and the highest abundance of terminal deoxynucleotidyl transferase dUTP nick end labeling+ (TUNEL+) apoptotic cells among the experiment groups. Minimal treatment-associated toxicity was observed. Our findings suggest that neutrophil-mediated delivery of chemotherapy drugs is a useful tool to enhance the response of pancreatic cancer to IRE.

Palladium-Catalyzed Annulative π-Extension of Bay-Iodinated Triphenylenes to Access Polycyclic Aromatic Compounds.

A palladium-catalyzed annulative π-extension reaction of bay-iodinated triphenylenes with aryl iodides/o-chloroaromatic carboxylic acids was developed. This approach enabled the synthesis of diverse polycyclic aromatic compounds, including dibenzo[fg,op]tetracenes, azadibenzo[fg,op]tetracenes, and tribenzo[a,g,m]coronenes. Initial studies indicate that the resulting product, 2,3,8,9,14,15-hexakis(decyloxy)tribenzo[a,g,m]coronene, exhibits good liquid-crystalline properties.

Anti-oxidant activity of 1-(1H-imidazo[4,5-c]pyridin-4-yl)ethenone, a Maillard reaction product derived from fructose and histidine.

BACKGROUND: The Maillard reaction involves the interaction of various amino acids and reducing sugars, resulting in food browning. It often produces appealing aromas and flavors. The complexities of the reaction are such that it can be challenging to identify the often numerous and frequently volatile products formed by it. In the present study, we sought to identify and evaluate an unusual product with anti-oxidant activity arising from a fructose-histidine Maillard reaction model. The anti-oxidant profile of this product was assessed by computational means. RESULTS: The fructose-histidine Maillard reaction products (FH-MRPs) were generated by heating a 2:1 mixture of the sugar and the amino acid at 140 °C for 2 h. Chromatographically separable fractions, labelled DM-1 to DM-8, were obtained using silica gel as the stationary phase and dichloromethane/methanol (DCM/MeOH) mixtures as the mobile one. Fraction DM-5 exhibited the highest 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, and further bio-assay guided fractionation led to isolation and identification of 1-(1H-imidazo[4,5-c]pyridin-4-yl)ethenone (IMPE) as the active principal, the structure of which was established by nuclear magnetic resonance (NMR) spectroscopic and mass spectral techniques. A mechanism for the formation of IMPE from its precursors is proposed. Density functional theory (DFT) calculations suggest this novel heterocyclic compound exerts its anti-oxidant effects by interacting with DPPH and 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radicals. Essentially, IMPE was non-toxic below 300 ug mL-1, showing a concentration-dependent free radical clearance capacity and reducing power within the 100-1000 µg mL-1 range, and moreover, exhibiting significant Fe2+ chelating abilities wihin the 50-200 µg mL-1 range. CONCLUSION: This study identified the unique FH-MRP, IMPE, and found that it acts as food antioxidant through the chelation of metal ions. © 2024 Society of Chemical Industry.

Biogenic volatile organic compounds dominated the near-surface ozone generation in Sichuan Basin, China, during fall and wintertime.

The complex air pollution driven by both Ozone (O3) and fine particulate matter (PM2.5) significantly influences the air quality in the Sichuan Basin (SCB). Understanding the O3 formation during autumn and winter is necessary to understand the atmospheric oxidative capacity. Therefore, continuous in-site field observations were carried out during the late summer, early autumn and winter of 2020 in a rural area of Chongqing. The total volatile organic compounds (VOCs) concentration reported by a Proton-Transfer-Reaction Time-of-Flight Mass Spectrometry (PTR-ToF-MS) were 13.66 ± 9.75 ppb, 5.50 ± 2.64 ppb, and 9.41 ± 5.11 ppb in late summer, early autumn and winter, respectively. The anthropogenic VOCs (AVOCs) and biogenic VOCs (BVOCs) were 8.48 ± 7.92 ppb and 5.18 ± 2.99 ppb in late summer, 3.31 ± 1.89 ppb and 2.19 ± 0.93 ppb in autumn, and 6.22 ± 3.99 ppb and 3.20 ± 1.27 ppb in winter. A zero-dimensional atmospheric box model was employed to investigate the sensitivity of O3-precursors by relative incremental reactivity (RIR). The RIR values of AVOCs, BVOCs, carbon monoxide (CO), and nitrogen oxides (NOx) were 0.31, 0.71, 0.09, and -0.36 for late summer, 0.24, 0.59, 0.22, and -0.38 for early autumn, and 0.30, 0.64, 0.33 and -0.70 for winter, and the results showed that the O3 formation of sampling area was in the VOC-limited region, and O3 was most sensitive to BVOCs (with highest RIR values, > 0.6). This study can be helpful in understanding O3 formation and interpreting the secondary formation of aerosols in the winter.

TRPC6 promotes daunorubicin-induced mitochondrial fission and cell death in rat cardiomyocytes with the involvement of ERK1/2-DRP1 activation.

Daunorubicin (DNR-) induced cardiotoxicity seriously restricts its clinical application. Transient receptor potential cation channel subfamily C member 6 (TRPC6) is involved in multiple cardiovascular physiological and pathophysiological processes. However, the role of TRPC6 anthracycline-induced cardiotoxicity (AIC) remains unclear. Mitochondrial fragmentation greatly promotes AIC. TRPC6-mediated ERK1/2 activation has been shown to favor mitochondrial fission in dentate granule cells. The aim of the present study was to elucidate the effects of TRPC6 on daunorubicin- induced cardiotoxicity and identify the mechanisms associated with mitochondrial dynamics. The sparkling results showed that TRPC6 was upregulated in models in vitro and in vivo. TRPC6 knockdown protected cardiomyocytes from DNR-induced cell apoptosis and death. DNR largely facilitated mitochondrial fission, boosted mitochondrial membrane potential collapse and damaged debilitated mitochondrial respiratory function in H9c2 cells，these effects were accompanied by TRPC6 upregulation. siTRPC6 effectively inhibited these mitochondrial adverse aspects showing a positive unexposed effect on mitochondrial morphology and function. Concomitantly, ERK1/2-DRP1 which is related to mitochondrial fission was significantly activated with amplified phosphorylated forms in DNR-treated H9c2 cells. siTRPC6 effectively suppressed ERK1/2-DPR1 over activation, hinting at a potential correlation between TRPC6 and ERK1/2-DRP1 by which mitochondrial dynamics are possibly modulated in AIC. TRPC6 knockdown also raised the Bcl-2/Bax ratio, which may help to block mitochondrial fragmentation-related functional impairment and apoptotic signaling. These findings suggested an essential role of TRPC6 in AIC by intensifying mitochondrial fission and cell death via ERK1/2-DPR1, which could be a potential therapeutic target for AIC.

IL-17A plays a critical role in RSV infection in children and mice.

BACKGROUND: IL-17A is a pleiotropic cytokine and intimately associated with asthma, but its role in respiratory syncytial virus (RSV) infection is conflicting in the literature. METHODS: Children hospitalized in the respiratory department with RSV infection during RSV pandemic season of 2018-2020 were included. Nasopharyngeal aspirates were collected for pathogen and cytokines determination. In the murine model, RSV intranasal administrations were performed in wild-type and IL-17A-/- mice. Leukocytes and cytokines in bronchoalveolar lavage fluid (BALF), lung histopathology, and airway hyperresponsiveness (AHR) were measured. RORγt mRNA and IL-23R mRNA were semi-quantified by qPCR. RESULTS: IL-17A increased significantly in RSV-infected children and was positively associated with pneumonia severity. In the murine model, IL-17A significantly increased in BALF of mice with RSV infection. Airway inflammation, lung tissue damage and AHR were significantly alleviated in wild-type mice following IL-17A neutralization and in the IL-17A-/- mice. IL-17A decreased by removing CD4+ T cells but increased by depleting CD8+ T cells. IL-6, IL-21, RORγt mRNA and IL-23R mRNA dramatically increased in parallel with the rise of IL-17A. CONCLUSIONS: IL-17A contributes to the airway dysfunctions induced by RSV in children and murine. CD3+CD4+T cells are its major cellular sources and the IL-6/IL-21-IL-23R-RORγt signaling pathway might participate in its regulation.

The transversus abdominis plane block in conjunction with intrathecal morphine use after cesarean section in women with severe pre-eclampsia: a randomized controlled trial.

BACKGROUND: The transversus abdominis plane (TAP) block in conjunction with intrathecal morphine has been demonstrated to provide more superior postcesarean analgesia to intrathecal morphine alone. However, the analgesia efficacy of their conjunction has not been demonstrated in patients with severe pre-eclampsia. The study aimed to compare the postcesarean analgesia of TAP block in conjunction with intrathecal morphine versus intrathecal morphine alone in women with severe pre-eclampsia. METHODS: Pregnant women with severe pre-eclampsia undergoing planned cesarean section were randomly allocated into 2 groups to receive TAP block with 20 ml of 0.35% Ropivacaine (TAP group) or with the same volume of 0.9% saline (Sham group) after undergoing elective cesarean section under spinal anaesthesia with 15 mg of 0.5% Ropivacaine plus 0.1 mg of morphine. The outcomes for this analysis include the visual analog scale (VAS) pain score at rest and with movement at 4,8,12,24 h after TAP block was performed, times of use of intravenous patient-controlled analgesia (PCA) within 12 h after anesthesia, the occurrence of maternal side effects, maternal satisfaction, and Apgar score at 1 and 5 min of newborns. RESULTS: 119 subjects receive TAP block with 0.35% Ropivacaine (n = 59)or 0.9% saline (n = 60). At 4,8, 12 h after TAP block, the TAP group reported lower VAS score at rest [at 4 h: 1(0,1) vs. 1(1,2), P < 0.001; at 8 h:1(1,1) vs. 1(1.5,2),P < 0.001; at 12 h:1(1,2) vs. 2(1,2),P = 0.001] and higher satisfaction [53(89.9%) vs.45(75.0%), P < 0.05]. There were no differences between groups in VAS score at 24 h at rest and at all time points above with movement, times of use of PCA within 12 h after anesthesia, maternal side-effect, and Apgar score at 1 and 5 min of newborns. CONCLUSIONS: In conclusion, The TAP block performed in conjunction with intrathecal morphine may not reduce opioid consumption, but it could reduce VAS scores at rest in the first 12 h after cesarean section in women with severe pre-eclampsia, and improve maternal satisfaction, which is worthy of clinical promotion. TRIAL REGISTRATION: Registered at Chinese Clinical Trial Registry( http://www.chictr.org.cn ) on 13/12/2021: ChiCTR2100054293.

Tuning the Metal Ions of Prussian Blue Analogues in Separators to Enable High-Power Lithium Metal Batteries.

The Li dendrite issue is the major barrier that limits the implement of Li metal anode practically, especially at high current density. From the perspective of the nucleation and growth mechanism of the Li dendrite, we rationally develop a novel Prussian blue analogues (PBA)-derived separator, where tuning the metal ions bestows the PBAs with open metal site to confine anion movement and thereby afford a high Li+ transference number (0.78), and PBA with ordered micropores could act as an ionic sieve to selectively extract Li+ and thereby homogenize Li+ flux. This demonstrates a highly reversible Li plating/stripping cycling for 3000 h at a practically high current density (5.0 mA cm-2). Consequently, a high loading Li||LiFeO4 battery (∼10.0 mg cm-2) demonstrates ultralong cycling life at high current densities (∼5.1 mA cm-2). This work highlights the prospect of optimizing PBAs in regulating ion transport behavior to enable high-power Li metal batteries.

[Clinical appraisal of laparoscopic inguinal lymphadenectomy with preservation of the great saphenous vein through subcutaneous approach via umbilical cord for the treatment of penile carcinoma: Report of 27 cases].

OBJECTIVE: To explore the clinical efficacy and advantages of laparoscopic inguinal lymphadenectomy (IL) with preservation of the great saphenous vein through subcutaneous approach via umbilical cord for the treatment of penile carcinoma patients. METHODS: The data of 27 patients with penile cancer underwent the laparoscopic inguinal lymph adenectomy with preservation of the great saphenous vein through subcutaneous via umbilical cord approach in the General Hospital of Eastern Theater Command from 2014 May to 2022 May were analyzed retrospectively.All patients underwent partial penile resection, with a pathological diagnosis of squamous cell carcinoma and 20 cases were highly differentiated, 7 cases were moderately differentiated, with the average age was 54 ± 7.5 years old. All patients were in supine position, and a subcutaneous space was established under visualization to establish a laparoscopic operation channel. The scope of cleaning included the superficial and deep inguinal lymph nodes, while the key aspects of the procedure was the preservation of the main trunk of the great saphenous vein. The external boundary of bilateral inguinal lymph node dissection was the line between the anterior superior iliac spine and 20cm lower, the inner boundary was pubic tubercle and its 15cm medical lower measurement, and the line between the inner boundary and the external lower edge was the lower boundary. RESULT: All the 27 patients were successfully completed without transfer to open surgery. The average operation time was (115 ± 26) minutes, the average blood loss during operation was (40 ± 8) ml, postoperative hospital stays was (6.8 ± 1.5) days, and postoperative drainage tube removal time was (6.4 ± 1.2) days. The average number of lymph nodes was 12.5 (5-21) on the left side, and 11.4 (2-19) on the right side. No skin necrosis and subcutaneous hematoma was occurred in all patients. Three patients had postoperative lymphatic leakage and two patients had lymphatic cysts. All patients were cured by conservation treatment. No recurrence and metastasis were occurred during 14-28 months follow up postoperatively. Conclusion： Laparoscopic inguinal lymphadenectomy with preservation of the great saphenous vein through subcutaneous approach via umbilical cord can achieve the expected surgical outcome. It has some advantages of shorter operation time, less blood loss，low incidence of complication ,especially avoid skin flap necrosis and subcutaneous hematoma．.

Low threshold optical bistability based on topological edge state in photonic crystal heterostructure with Dirac semimetal.

The special band structure of three-dimensional Dirac semimetal (3D DSM) makes it show strong nonlinear optical characteristics in the terahertz region, which provides a new way to develop terahertz nonlinear devices with low threshold. In this paper, we theoretically study the optical bistability (OB) of transmitted light in a multilayer structure with 3D DSM embedded in two one-dimensional photonic crystals (1D PhC). The topological edge state (TES) excited by the 1D PhC heterostructure significantly enhances the local electric field near the nonlinear 3D DSM, which provides a positive condition for the realization of low threshold OB. Through parameter optimization, we obtain a threshold electric field with an incident electric field of 106 V/m levels. Furthermore, the influences of the Fermi energy and thickness of 3D DSM and the angle of the incident light on the hysteretic behavior as well as the threshold of OB are clarified. 3D DSM-based optical devices with intrinsic OB provide a building block for future integrated optical and all-optical networks.

Efficient Atmospheric Transport of Microplastics over Asia and Adjacent Oceans.

We developed a regional atmospheric transport model for microplastics (MPs, 10 µm to 5 mm in size) over Asia and the adjacent Pacific and Indian oceans, accounting for MPs' size- and shape-dependent aerodynamics. The model was driven by tuned atmospheric emissions of MPs from the land and the ocean, and the simulations were evaluated against coastal (n = 19) and marine (n = 56) observations. Our tuned atmospheric emissions of MPs from Asia and the adjacent oceans were 310 Gg y-1 (1 Gg = 1 kton) and 60 Gg y-1, respectively. MP lines and fragments may be transported in the atmosphere >1000 km; MP pellets in our model mostly deposited near-source. We estimated that 1.4% of the MP mass emitted into the Asian atmosphere deposited into the oceans via atmospheric transport; the rest deposited over land. The resulting net atmospheric transported MP flux from Asia into the oceans was 3.9 Gg y-1, twice as large as a previous estimate for the riverine-transported MP flux from Asia into the oceans. The uncertainty of our simulated atmospheric MP budget was between factors of 3 and 7. Our work highlighted the impacts of the size and morphology on the aerodynamics of MPs and the importance of atmospheric transport in the source-to-sink relationship of global MP pollution.

Risk factors associated with reintubations in children undergoing foreign body removal using flexible bronchoscopy: a single-center retrospective cross-sectional study.

BACKGROUND: Reintubation is a severe complication during foreign body (FB) removal that uses flexible bronchoscopy. OBJECTIVE: To investigate the incidence and risk factors for reintubations in children undergoing FB extraction by flexible bronchoscopy in a single center. DESIGN: A retrospective cross-sectional study. SETTING: All children with foreign body aspiration at Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University from January 2015 to December 2020. PATIENTS: Children with FB removal using a flexible bronchoscopy were enrolled in the trial according to the inclusion criteria. MEASUREMENTS: Both multivariable and logistic regression analyses were used to analyze the association between characteristic data and reintubations. The results were presented as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In total, 244 patients met with the inclusion criteria and were included in the analysis. Among those participants, 28 children (11.5%) underwent reintubations after FB removal by flexible bronchoscopy. Independent factors associated with reintubations were identified as operative time ≥ 60 min [OR: 3.68, 95% CI (1.64-8.82)] and ASA ≥ III [OR: 5.7, 95% CI (1.23-26.4)]. CONCLUSIONS: Children undergoing FB removal by a flexible bronchoscopy may encounter with a high incidence of postoperative reintubations. Both long operative duration and a severe physical status cause a growing risk of reintubations.

The role of routine laboratory tests after unilateral total knee arthroplasty.

BACKGROUND: Recent studies suggest that routine laboratory tests are not required within 1 day after partial knee arthroplasty. In this study, we evaluated the utility of routine postoperative laboratory tests after initial unilateral total knee arthroplasty (TKA) in an Asian population. In addition, we explored risk factors associated with abnormal test results. METHODS: Clinical data of patients who underwent original unilateral TKA between 2015 and 2020 were retrospectively analyzed. Patient characteristics and laboratory test results were recorded. Multivariate binary logistic regression analysis was performed to identify risk factors associated with 3 abnormal laboratory results. RESULTS: A total of 713 patients, who underwent relevant laboratory tests within 3 days of TKA surgery, were enrolled. Among them, 8.1%, 9.9%, and 3.4% patients with anemia, hypoalbuminemia, and abnormal serum potassium levels required clinical intervention after surgery. Binary logistic regression analysis revealed that preoperative hemoglobin levels, estimated blood loss, and age were independent risk factors of postoperative blood transfusion in TKA patients. On the other hand, preoperative albumin levels, intraoperative blood loss, and operation time were risk factors associated with postoperative albumin supplementation. In addition, lower body mass index (BMI) and preoperative hypokalemia were potential risk factors of postoperative potassium supplementation. CONCLUSION: Considering that more than 90% of abnormal postoperative laboratory tests do not require clinical intervention, we believe that routine laboratory tests after surgery have little significance in patients with primary unilateral TKA. However, postoperative laboratory testing is necessary for patients with established risk factors.

Harnessing Natural Products by a Pharmacophore-Oriented Semisynthesis Approach for the Discovery of Potential Anti-SARS-CoV-2 Agents.

Natural products possessing unique scaffolds may have antiviral activity but their complex structures hinder facile synthesis. A pharmacophore-oriented semisynthesis approach was applied to (-)-maoelactone A (1) and oridonin (2) for the discovery of anti-SARS-CoV-2 agents. The Wolff rearrangement/lactonization cascade (WRLC) reaction was developed to construct the unprecedented maoelactone-type scaffold during semisynthesis of 1. Further mechanistic study suggested a concerted mechanism for Wolff rearrangement and a water-assisted stepwise process for lactonization. The WRLC reaction then enabled the creation of a novel family by assembly of the maoelactone-type scaffold and the pharmacophore of 2, whereby one derivative inhibited SARS-CoV-2 replication in HPA EpiC cells with a low EC50 value (19±1 nM) and a high TI value (>1000), both values better than those of remdesivir.

Clearable Nanoparticles for Cancer Photothermal Therapy.

Nanoparticles are important mediators for cancer photothermal therapy (PTT) where they can efficiently convert photon energy into heat and ablate the surrounding cancer cells with superior spatial and temporal precision. Recent decades have witnessed a booming development of numerous formulations of PTT nanoparticles that exhibit outstanding anti-tumor efficacy in preclinical studies. However, their clinical translation has been mined by safety concerns, especially their long-term impact on human body. Biodegradable nanoparticles that can be excreted after PTT, therefore, are gaining popularity due to their biocompatibility and improved safety profiles. This chapter provides an update on the progress in clearable PTT nanoparticles for cancer treatment. We discuss their design, synthesis strategy, and physicochemical properties relevant to photothermal performance. We also review their biodistribution patterns and in vivo anti-tumor efficacy, along with their degradation mechanism and clearance kinetics. Lastly, we present a brief overview of the imaging techniques to noninvasively monitor the degradation of PTT nanoparticles.

ACE2 Expression in Pancreas May Cause Pancreatic Damage After SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel coronavirus that causes coronavirus disease 2019 (COVID-19) in human beings, has caused a serious public health issue.1 Attention to pancreatic injury is lacking, which may impact patients' prognosis. In this study, we explored the expression and distribution of angiotensin-converting enzyme 2 (ACE2), the receptor of SARS-CoV-2, in the pancreas. Combined with clinical data, we showed that pancreatic injury can occur in some COVID-19 patients.