Uncertainties around net-zero climate targets have major impact on greenhouse gas emissions projections.

Globally, more than 100 countries have adopted net-zero targets. Most studies agree on how this increases the chance of keeping end-of-century global warming below 2°C. However, they typically make assumptions about net-zero targets that do not capture uncertainties related to gas coverage, sector coverage, sinks, and removals.

Boosting the enzymatic activity of CxxC motif-containing PDI family members.

Compounds harboring high acidity and oxidizability of thiol groups permit tuning the redox equilibrium constants of CxxC sites of members of the protein disulphide isomerase (PDI) family and thus can be used to accelerate folding processes and increase the production of native proteins by minimal loading in comparison to glutathione.

Rapid Generation of Murine Bispecific Antibodies Using FAST-Ig for Preclinical Screening of HER2/CD3 T-Cell Engagers.

Bispecific antibodies (BsAbs) can bind to two different antigens, enabling therapeutic concepts that cannot be achieved with monoclonal antibodies. Immuno-competent mice are essential for validating drug discovery concepts, necessitating the development of surrogate mouse BsAbs. In this study, we explored the potential of FAST-Ig, a previously reported BsAb technology, for mouse BsAb production.

Characterizations of a neutralizing antibody broadly reactive to multiple gluten peptide:HLA-DQ2.5 complexes in the context of celiac disease.

In human celiac disease (CeD) HLA-DQ2.5 presents gluten peptides to antigen-specific CD4 T cells, thereby instigating immune activation and enteropathy. Targeting HLA-DQ2.

Effects of tramadol via a µ-opioid receptor on pancreatic ductal adenocarcinoma in vitro and in vivo.

Introduction: Tramadol, a weak opioid anesthetic, is used for pain management in patients with cancer, but the effects of tramadol on cancer via µ-opioid receptor are still unknown. We assessed the effects of tramadol on pancreatic ductal adenocarcinoma using transgenic mice ( ).

Methods: Six-week-old transgenic mice were orally administered 10 mg/kg/day tramadol (n=12), 10 mg/kg/day tramadol and 1 mg/kg/day naltrexone (n=9), or vehicle water (n=14) until the humane endpoint.

Efficient production of bispecific antibody by FAST-Ig and its application to NXT007 for the treatment of hemophilia A.

Efficient production of bispecific antibodies (BsAbs) in single mammalian cells is essential for basic research and industrial manufacturing. However, preventing unwanted pairing of heavy chains (HCs) and light chains (LCs) is a challenging task. To address this, we created an engineering technology for preferential cognate HC/LC and HC/HC paring called FAST-Ig (Four-chain Assembly by electrostatic Steering Technology - Immunoglobulin), and applied it to NXT007, a BsAb for the treatment of hemophilia A.

Credibility gap in net-zero climate targets leaves world at high risk.

Looking at policies instead of promises shows that global climate targets may be missed by a large margin.

Genetic characterization of Dibothriocephalus latus and Dibothriocephalus dendriticus (Cestoda: Diphyllobothriidae) from Chile based on haplotype analysis using mitochondrial DNA markers.

Dibothriocephalus latus and Dibothriocephalus dendriticus are found throughout the temperate and sub-arctic zones of the northern hemisphere, but they are also found in the southern core countries of South America, Chile and Argentina. Genetic characteristics of D. latus and D.

Long-Term Analgesic Efficacy of Neurolytic Splanchnic Nerve Block via the Transintervertebral Disc Approach to Retrocrural Space: A Multicenter Retrospective Study.

Introduction: The celiac plexus block is effective for treating intractable cancer pain and has been the focus of many studies. At our affiliated institution, fluoroscopy-guided splanchnic nerve block with a single needle via the transintervertebral disc approach was the first choice of treatment. The short-term efficacy of this technique has been reported, but the long-term efficacy is not clear.

Mirogabalin improves cancer-associated pain but increases the risk of malignancy in mice with pancreatic cancer.

Mirogabalin, a selective voltage-gated calcium channel α2δ ligand, improves peripheral neuropathic pain; however, its effects on patients with cancers including pancreatic ductal adenocarcinoma (PDAC) remain unknown. We analyzed the effects of mirogabalin on a KPPC ( LSL-KrasG12D/+; Trp53flox/flox; Pdx-1cre/+ ) mouse model of PDAC. Six-week-old KPPC mice received oral mirogabalin (10 mg/kg/day) (n = 10) or vehicle water (n = 14) until the humane end point.

Opioid withdrawal symptoms after neurolytic splanchnic nerve block in cancer patients.

Purpose: Few reports on opioid withdrawal (OW) due to opioid tapering in cancer patients have been published. The incidence of and risk factors for OW after neurolytic splanchnic nerve block (NSNB) are unknown. This study aimed to elucidate the incidence of and risk factors for OW among cancer patients who could have reduced opioid doses after NSNB.

Efficacy and Safety of Neurolytic Splanchnic Nerve Block via Transintervertebral Disc Approach to Retrocrural Space: A Multicenter Retrospective Study.

Introduction: Celiac plexus block is effective for treating intractable cancer pain and has been the focus of many studies. Several guiding techniques such as fluoroscopy, computed tomography, and endoscopy have been devised, and the target of the block has varied in previous studies as both the celiac plexus and splanchnic nerve, which is the main origin of the celiac plexus, have been targeted. At our affiliated institution, fluoroscopy-guided splanchnic nerve block with a single needle via transintervertebral disc approach is the first choice.

The G20 emission projections to 2030 improved since the Paris Agreement, but only slightly.

Unlabelled: Many years passed since the adoption of the Paris Agreement, which invites countries to determine their own contributions to climate change mitigation efforts. The Agreement does not offer a standard to measure progress but relies on a process of periodic stocktakes to inform ambition-raising cycles. To contribute to this process, we compare 2021 greenhouse gas emission projections up to 2030 against equivalent projections prepared back in 2015.

Updated nationally determined contributions collectively raise ambition levels but need strengthening further to keep Paris goals within reach.

Unlabelled: By January 2022, 156 countries had submitted new or updated nationally determined contributions (NDCs) under the Paris Agreement. This study analyses the greenhouse gas (GHG) emissions and macroeconomic impacts of the new NDCs. The total impact of the updated unconditional and conditional NDCs of these countries on global emission levels by 2030 is an additional reduction of about 3.

Elimination of plasma soluble antigen in cynomolgus monkeys by combining pH-dependent antigen binding and novel Fc engineering.

A conventional antibody targeting a soluble antigen in circulation typically requires a huge dosage and frequent intravenous administration to neutralize the antigen. This is because antigen degradation is reduced by the formation of antigen-antibody immune complexes, which escape from lysosomal degradation using neonatal Fc receptor (FcRn)-mediated recycling. To address this, we developed an antigen-sweeping antibody that combines pH-dependent antigen binding and Fc engineering to enhance Fc receptor binding.

Comprehensive engineering of a therapeutic neutralizing antibody targeting SARS-CoV-2 spike protein to neutralize escape variants.

The emergence of escape variants of SARS-CoV-2 carrying mutations in the spike protein poses a challenge for therapeutic antibodies. Here, we show that through the comprehensive engineering of the variable region of the neutralizing monoclonal antibody 5A6, the engineered antibody, 5A6CCS1, is able to neutralize SARS-CoV-2 variants that escaped neutralization by the original 5A6 antibody. In addition to the improved affinity against variants, 5A6CCS1 was also optimized to achieve high solubility and low viscosity, enabling a high concentration formulation for subcutaneous injection.

Midazolam exhibits antitumour and anti-inflammatory effects in a mouse model of pancreatic ductal adenocarcinoma.

Background: Anaesthesia and perioperative management contribute to long-term outcomes of patients with cancer, including pancreatic ductal adenocarcinoma. We assessed the antitumour, anti-inflammatory, and analgesic effects of midazolam on LSL-Kras;Trp53;Pdx-1 transgenic mice with pancreatic ductal adenocarcinoma.

Methods: Six-week-old transgenic mice were administered midazolam 30 mg kg day p.

Can updated climate pledges limit warming well below 2°C?

Increased ambition and implementation are essential.

Effect of contrast medium versus low-molecular-weight dextran for intracoronary optical coherence tomography in renal insufficiency.

Low-molecular-weight dextran (LMWD) is considered a safe alternative to contrast media to displace blood during optical coherence tomography (OCT) imaging, but concerns remain. The purpose of this study was to investigate whether using LMWD for OCT protects against kidney injury in patients with renal insufficiency compared with contrast media. We retrospectively identified 474 patients with renal insufficiency (estimated glomerular filtration rate < 60 ml/min/1.

Novel myostatin-specific antibody enhances muscle strength in muscle disease models.

Myostatin, a member of the transforming growth factor-β superfamily, is an attractive target for muscle disease therapy because of its role as a negative regulator of muscle growth and strength. Here, we describe a novel antibody therapeutic approach that maximizes the potential of myostatin-targeted therapy. We generated an antibody, GYM329, that specifically binds the latent form of myostatin and inhibits its activation.

Infestation of the Parasitic Isopod on Juveniles of the Black Sea Bream as an Optional Intermediate Host in Hiroshima Bay.

In Hiroshima Bay, parasitic isopods of the genus infest the black sea bream (Bleeker, 1854) and the Japanese halfbeak (Temminck and Schlegel, 1846), two fish species that are abundant and commercially important in the Seto Inland Sea of Japan. Immature and mature individuals can infect both juveniles and adults of , while immature are known to parasitize juveniles of ; i.e.

Ventricular Fibrillation During Optical Coherence Tomography/Optical Frequency Domain Imaging - A Large Single-Center Experience.

Background: The risks of ventricular fibrillation (Vfib) associated with frequency-domain optical coherence tomography (OCT)/optical frequency domain imaging (OFDI) remain undetermined.

Methods and results: We retrospectively studied the occurrence of Vfib during OCT/OFDI for unselected indications. The frequency of Vfib and patient and procedural characteristics were investigated.

Infection status of commercial fish with cystacanth larvae of the genus Corynosoma (Acanthocephala: Polymorphidae) in Hokkaido, Japan.

Acanthocephalans of the genus Corynosoma are known as intestinal parasites, mainly of pinnipeds. Human corynosomiasis has been reported as an infrequent foodborne disease in Hokkaido, the northernmost island of Japan. Potential sources of the human infection are marine fish, because they are paratenic hosts of these parasites.